REVISTA

ROMÂNĂ

de

PSIHIATRIE

Vol XVIII Nr. 1 March 2016

QUARTERLY

CNCSIS B+ p-ISSN: 1454-7848 e-ISSN: 2068-7176

COMITET DE REDACŢIERedactor şef: Dan PRELIPCEANURedactor-şefi adjuncți: Dragoş MARINESCU Aurel NIREŞTEANCOLECTIV REDACŢIONALDoina COZMANLiana DEHELEANMarieta GABOŞ GRECUMaria LADEACristinel ŞTEFĂNESCUCătălina TUDOSE

Secretari de redacţie: Elena CĂLINESCU Valentin MATEI

CONSILIU ŞTIINŢIFIC Vasile CHIRIŢĂ (membru de onoare al Academiei de Ştiinţe Medicale, Iaşi)Michael DAVIDSON (Professor, Sackler

School of Medicine Tel Aviv Univ., Mount Sinai School of Medicine, New York)

Virgil ENĂTESCU (membru al Academiei de Ştiinţe Medicale, Satu Mare)

Ioana MICLUŢIA (UMF Cluj-Napoca)Şerban IONESCU (Universitatea

Paris VIII, Universitatea Trois-Rivieres, Quebec)

Mircea LĂZĂRESCU (membru de onoare al Academiei de Ştiinţe Medicale, Timisoara)

Juan E. MEZZICH (Professor of Psychiatry and Director, Division of Psychiatric Epidemiology and International Center for Mental Health, Mount Sinai School of Medicine, New York University)

Sorin RIGA (cercetător principal gr.I)

Eliot SOREL (George Washington University, Washington DC)

Maria GRIGOROIU-ŞERBĂNESCU (cercetător principal gr.I)

Tudor UDRIŞTOIU (UMF Craiova)

Teodor T. POSTOLACHE, MD (Director, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore)

Dan RUJESCU (Head of Psychiatric Genomics and Neurobiologyand of Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig- Maximilians-University, Munchen)

ARPP

ASOCIAŢIA ROMÂNĂDE PSIHIATRIE ŞI PSIHOTERAPIE

www.romjpsychiat.ro

ROMANIAN JOURNAL OF PSYCHIATRY

CUPRINS

ARTICOLE SPECIALE

& Dimensiunea spirituală a personalității și rolul său în sănătatea mintală 1

& Modelul integrativ al psihoterapiei cognitiv-comportamentale în tulburările de personalitate 4

& 8

& Ideație, comportament și tulburări de dispoziție în boala Parkinson - studiu clinic 11

ARTICOLE ORIGINALE

& Evoluția simptomatologiei și funcționalității la pacienți români cu episod

depresiv major - studiu observațional 15

& Tulburări psihice în epilepsia copilului 21

INSTRUCŢIUNI PENTRU AUTORI 25

Aurel Nireștean, Emese Lukacs, Gabriela Buicu, Monica Bilcă, Pokorny Vasile

Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu

Raluca Ileana Nica, Mihail Cristian Pîrlog

Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev, Ivan Manchev, Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi

Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog,

George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea,

Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu

Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila

ARTICOLE DE SINTEZĂ

Screening-ul depresiei la nivelul asistenței medicale primare - o intervenție cost-eficientă

Revista Română de Psihiatrie este indexată de Consiliul Naţional al Cercetării Ştiinţifice din Învăţământul Superior la categoria B+. Apare trimestrial.

Colegiul Medicilor din România acordă abonaţilor la această publicaţie 5 credite EMC/an.Articolele ştiinţifice publicate în revistă sunt creditate cu 80 credite EMC/articol.

Revista Română de Psihiatrie este editată de Asociaţia Română de Psihiatrie şi Psihoterapieşi Asociaţia Medicală Română

SPECIAL ARTICLES

THE SPIRITUAL DIMENSION OF PERSONALITY AND ITS ROLE IN MENTAL HEALTH

1, 2 3 4 5Aurel Nireștean Emese Lukacs , Gabriela Buicu , Monica Bilcă , Pokorny Vasile

The term “spirituality” continues to be the subject of great controversy. The diversity of its definitions corresponds to its complexity (Cook, Powell, Sims 2009). No matter the perspective, the spiritual world is a vast territory which integrates not only existential meanings and goals and affective and cognitive references, but also transpersonal beliefs and experiences which lead to a deeper understanding of the connection between psychic normality and abnormality and the normality and abnormality of the personality.Mental health is a global concept complementary to psychiatry which incorporates both a public health objective and a point of reference which is simultaneously individual and collective (Prelipceanu, Mihailescu, Teodorescu 2000). Thus, mental health promotes the totality of objective strategies which aim to protect the wellness of the community in both mind and spirit. It takes into account all the favorable factors, as well as the trigger factors for the diversity of psychic episodes and illnesses. A second component of mental health is the subjective individual and collective state of wellness which is a result of a harmonious personality which integrates and assumes life experiences in a coherent manner. They insure well-balanced interpersonal relationships as well as common access to authentic and liberating existential values.Knowledge of the governing principles of mental health becomes a major factor in the prevention of mental diseases and contributes decisively to eliminating the

stigma associated with mental illness and psychiatry in general. This is due to the fact that both mental wellness and mental illness are conditioned by biology, psychology and social culture, and thus must be discussed taking into account not only an individual's intentional subjectivity and ability to reflect, but also one's freedom to decide, act and transcend one's condition. Five centuries ago already, the description of a series of vaguely delineated and fleeting psychiatric entities showed the connection between psychiatry and the social and economic environment. Using the health biography of two brothers from Basel, who upon returning to their city of residence, recovered from a severe mental condition, Hofer describes “nostalgia”, a condition which subsequently became very well known in Western Europe. A couple of centuries later, several other fleeting clinical psychiatric conditions such as the hysterical and epileptic pathological fugues, were identified and described. They were called “ambulatory automatisms” in France, and “ambulatory determinisms” in Italy. At the end of the 20th century, “multiple personality” is described by Hacking (1995). The list of psychic disorders directly connected to socio-cultural dynamics can continue with impulse-control disorders, PTSD, and Gulf Syndrome which appeared after the Vietnam and Gulf Wars, as well as pathological post-traumatic states induced by certain sadistic abuses whose perpetrators have not been condemned as moral authors of the crime.

1 MD, PhD, Professor, Chief of Psychiatry Department, UMF Targu Mures 2MD, PhD, Assistant Professor, Psychiatry Clinic II, UMF Targu Mures3 MD, PhD, Lecturer, Psychiatry Department, UMF Targu Mures4 MD Psychiatry Resident, Psychiatry Clinic II, UMF Targu Mures5 PhD, Manager, Brancovenesti Psychiatry Hospital Received December 22, 2015, Revised January 13, 2016, Accepted January 21, 2016

Rezumat:Conceptul de sănătate mintală este unul global și complementar psihiatriei. Aceasta și pentru că boala psihică este adeseori o imagine deformată, caricaturală a sănătății mintale. Atât sănătatea cât și boala mintală implică corpul fizic, viața psihică dar și dimensiunea spirituală a persoanei. Ambele interferează cu datele biografice individuale și colective, cu tradițiile și obiceiurile comunitare dar și cu lumea valorilor culturale, religioase și morale. În abordarea sănătății mintale și a personalității individuale un rol major îl are perspectiva dimensională. Conform acesteia dimensiunile personalității favorizează acele experiențe spirituale care c re s c c a p a c i t ă ț i l e a d a p t a t i v e , f a v o r i z e a z ă autodeterminarea și reprezintă o modalitate de cultivare a acelor virtuți care protejează sănătatea mintală și permit ființei umane să respecte și lucrurile pe care nu le înțelege și care nu depind de ea.Cuvinte cheie: sănătate mintală, personalitate, dimensiune spirituală

Abstract:The concept of mental health is a global concept and is complementary to psychiatry. That is also because psychiatry disorder is often a deformed and caricatured image of mental health. Both mental health and psychiatric disorders implies physical body, psychism, as well as spiritual dimension of personality. Both of them interfere with individual and collective biography, with community traditions and customs, as well as with cultural, religious, and moral values. In the mental health and personality approaches the dimensional perspective plays a major role. According to this perspective, personality dimensions favor those spiritual experiences that enhance the coping abilities, self-determination, and are representing a way of cultivating those virtues which protect the mental health and allow the human being to respect also those things and events which don't depend of it.Key words: mental health, personality, spiritual dimension

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Mental health and psychic diseases must be discussed in terms of the self-conscious human being since they both deal with the biology, psyche, and spiritual values of the individual. Besides, the role of interpersonal relationships, autobiography and collective biography, community traditions and customs, cultural values and religion must always be discussed and emphasized.It is well known that contemporary society and culture are dominated by science, technology, religion, and community values which all inform, motivate and control the dynamics of contemporary life. Today's culture is one of overproduction and excessive consumption of goods and leisure. It promotes hedonistic living in the present moment as well as an individual's freedom to organize his or her life in a strictly subjective way. New models of success and false values which throw one's aspirations and motivations into disarray and confusion are constantly created. People communicate and befriend one-another through the internet where they are more likely to have superficial, soulless encounters. Though not everything is “proper”, everything is permitted, and promoting moral norms and trust in the law become optional (Nirestean 2009).Culture is more and more removed from universal symbols that give it cohesion. It promotes form over substance and it feeds it to a public who readily digests it without discernment. In the spirit of the “new democracy”, everything goes in a world overwhelmed by individualism, which prefers the winners to those who live wisely, no matter the means of their success.In contemporary society, human beings live for themselves and have a constant and insatiable desire for more. They make quick attempts at reaching peaks of real existential meanings, but are disadvantaged by selfishness and lack of self-control. The individual ego is hypertrophied but lacks substance. It turns within with an inauthentic and vulnerable self-esteem which is fed and sustained by a highly subjective interpretation of events and life experiences (Lipovetzky, 2007). This is the way human beings believe they can achieve the state of subjective wellbeing which is understood as a form of happiness- a main component of mental health.One's self-image and self-esteem condition each-other in the whirlwind of the search for the perfect moment, of competitiveness and competition, where altruism and empathy have become undesirable. Individual identity is thus built on rationality and knowledge, not on interpersonal harmony, faith, or spiritual experiences. The contemporary “Homo Democraticus” is very different from “Homo Spiritualis”. Nevertheless, knowledge can also bring about wisdom when human beings open up to spiritual values and espouse - even for narcissistic reasons- the way of good intentions.The structure of one's personality influences the somatic state of health- as is the case with certain cardio-vascular disease which are significantly affected- as well as one's psyche, in which it can be a breeding ground for addictions and a great diversity of psychic diseases. A mature personality takes coherent charge of its life experiences and has the ability to adapt to life's events and to its stress factors.From a conceptual perspective, mental health must be defined in connection with the various stages of life and its critical periods, and from an utilitarian viewpoint, it is

important to develop those factors which protect mental health and mental longevity.The most appropriate way to understand the connection between personality and mental health is to consider the points of reference of the dimensional perspective. The most commonly used are the ones belonging to the seven factors. For example, during adolescence, a heightened search for novelty and childhood sensations can lead to impulse-control disorders, addictive behavior as well as impulsivity and aggression. During puberty and adolescence, heightened levels of nervousness can facilitate the onset of the metabolic syndrome and of obesity in the years to follow, while being more conscientious protects one's health and longevity. Also during adolescence, having a pleasant, attitude and being conscientious can positively influence self-control and the ability to learn, and protect one's health as an adult. The frequency of negative life events, addictive behavior and mortality rates also diminish. On the contrary, a low level of self-control leads to diminished activity, impulse-control disorders, hetero-aggressiveness, as well as high rates of suicide upon reaching adulthood. At the adolescent stage, the progressive and elaborate access to human values has a positive effect on mental health, in contrast with the transitory access to inauthentic and fleeting values which are so often promoted in contemporary culture.In adults, having a high degree of nervousness, being unpleasant and not being conscientious can favor obesity, nicotine and alcohol addiction, as well as sustain a persistent pessimism and low self-esteem. On the contrary, being an extrovert means being active and sociable.The structure of the personality as well as the concept of mental health integrates biological, psychological, social and spiritual components. The subjectivity and intentionality of each individual are constantly completed and changed by one's spiritual needs which connect the individual with the world of the senses, of existential motivations, and self-transcendence. Spiritual needs reside at the foundation of the homonymous dimension of the personality. It molds together a diversity of attributes which are predominantly conditioned by culture, such as: intellectual abilities, curiosity, vision, originality, logic and depth, artistic and esthetic sense, wisdom, common sense, dignity, humor, but also the ability to control and transcend one's ego. Other major virtues of a spiritual person are tolerance, prudence, the ability to communicate, empathy, gratefulness, the ability to forgive and believe and respect that which we do not understand and which does not depend on us. This diversity of attributes of our spiritual being represents both a source of vitality and motivation, and a major framework of support for building self-esteem and a sense of belonging to the energy of the universe. They can also be said to represent a “divine calling” (Nirestean, 2011).In view of the above, the connection with the dominant attributes of mental wellness becomes evident. Among them are the self-control, the feeling of personal detachment, the ability to communicate intelligently and empathetically with those around you, the adaptability to stress and resilience or responsible involvement in one's life roles, accompanied by the ability to manage tasks

,Aurel Nireștean Emese Lukacs, Gabriela Buicu, Monica Bilcă, Pokorny Vasile The Spiritual Dimension Of Personality And Its Role In Mental Health

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which are seen as positive stimuli instead of sources of anxiety (Kobassa, Maddi, Zola, 1983). Optimism and self-assertion- which integrates both the ability to choose a professional option and that of developing feelings of friendship and love, are to be added to the list of characteristics of a mentally stable human being. The complex notion of mental wellness also includes the capacity to access the traditions and products of culture, faith and religion- mystical experiences being among those that confirm the unity of all things... A corollary of this diverse mental health structure is the state of subjective wellbeing with its two components, the cognitive and the affective. This “type of happiness” is fifty percent dependent on the quality of one's life and circumstances, but the rest correlates in an obvious manner to the dimensions of one's personality. Thus, high levels of neuroticism negatively affect the subjective wellbeing, while high levels of neuroticism stimulate it. Low levels of neuroticism allow for the growth of personal aptitudes and talents, and a rise in self-control. They also diminish addictive tendencies, stimulate vigilance, activism, empathy in interpersonal relationships, and group cohesion due to higher correctness and cooperation. The individual's moral stance is also enhanced, as he or she can only become whole and gain self-worth by being surrounded by others.In the same context, when one is more pleasant, conscientious and outgoing, one is more likely to be also be drawn by meditation, the sacred, and prayer which often enhances one's ability for self-transcendence. A variety of spiritual experiences are enhanced, which in their turn shape and mobilize these dimensions of the personality.In general, the growth in spirituality significantly influences the individual's psyche and behavior. People with a rich spiritual life can easily decide that God or Heaven is with them, and thus develop self-confidence and self-respect. Supportive, optimistic attitudes, thus sociability sustained by empathy and confidentiality in interpersonal relationships, are also influenced positively. The quality and duration of marriages grows, and in its turn favors longevity and the quality of life. It is a well known fact that the latter are clearly affected in people who live alone.Efficiency and creativity are dominant behaviors, and thus the conditions necessary to living a purposeful life are always present. Consequently, periods of personal satisfaction are more frequent, and existential meanings and motivations diversify. Under these conditions, self-image and subjective wellbeing are enhanced and positively condition each-other and can shape narcissistic type tendencies. Structured in this manner, they have an obvious adaptive role to play, and create a protective framework against various psychic episodes and illnesses as well as behavioral disorders including suicide.

Nurturing one's talents as well as spiritual practice- including religious practice- have an obvious therapeutic and rehabilitative non-medical role to play in one's psychological state of being because they contribute to the awareness of illness and one's attitude towards it, even in extreme situations. It also enhances one's attitude of compliance to therapy. This role holds true not only for the superstitions and beliefs of proto-religions, but also under the conditions of religious liberalism and syncretism of contemporary society. All of the above show the complexity of the concept of mental wellness in which the physical person, the psyche, society and the supernatural coalesce.Mental health is in the end a major attribute of human beings which is protected by the dimensions of personality such as, emotional balance, perseverance, imagination, common sense, wisdom, humor, faith, and the ability to transcend by accessing the sacred and the supernatural. This vast concept constitutes a major existential ideal, not only because "When God wants to punish humans, He first takes their minds away."Mature and truly self-aware individuals sometimes ask questions such as, "What is really important in life?"; What can help us through difficulties?"; "Where and under what conditions do we feel good about ourselves?" "Are we capable of true faith or aligning ourselves with spiritual values?" For those who practice psychiatry, an exchange of ideas and experiences with priests, monks and spiritual counselors would certainly be of great value in answering these types of questions.From the perspective of spiritual values, the concept of mental health- like the concept of personality- pleads for the union of man, society, nature and the universe. It is confirmed that spiritual beings have both a divine, contemplative, profound nature, and one that is worldly, and the union of the two can lead to all that is good, beautiful, right, emotionally supported and open toward transcendence in human existence. The harmony between the two teaches us to live “with something” and not “for something”, and gives us the freedom and authenticity which are being so strongly challenged in our world today.

REFERENCES1.Cook C, Powell A, Sims A. Spirituality and psychiatry.London: RCPsych Publications, 20092.Prelipceanu D, Mihailescu R, Teodorescu R (sub red.).Tratat de sanatate mintala. Vol.I. Bucuresti: Editura Enciclopedica, 20003.Hacking I. Rewriting the Soul: Multiple Personality and the Sciences of Memory. Princeton: Princeton Univ.Press, 19954.Nirestean A (sub red.). Personalitate si deschidere spirituala. Targu Mures: University Press, 20095. Lipovetzky G. Fericirea paradoxala. Iasi: Editura Polirom, 20076. Nirestean A (sub red.). Personalitate, credinte si religii. Targu Mures: University Press, 20117. Kobasa SC, Maddi SR, Zola MA. Type A and hardiness. Journal of Behavioral Medicine 6 (1): 41–51(1983).

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Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

REVIEW ARTICLES

THE INTEGRATIVE MODEL OF COGNITIVE-BEHAVIORAL PSYCHOTHERAPY IN PERSONALITY DISORDERS

1 2 3 4Cosmin O. Popa , Mihai Ardelean , Tudor Nireștean , Gabriela Buicu

INTRODUCTIONThe current cognitive behavioral therapy

(CBT) paradigm starts from an integrative model that is based on the scientifically proven effectiveness in the psychological treatment of personality disorder (PD) treatments, some therapeutic strategies being derived from other psychotherapeutic guidelines. Thus, CBT is the integrative framework which could facilitate the c o n n e c t i o n b e t w e e n p s y c h o l o g i c a l a n d pharmacotherapeutic treatments whenever there is scientific support for this co-association. It however, requires a revision of these integrative issues but it is well-known currently that the treatment of choice of PDs is psychological interventions (1).

Personality disorders can be defined as sustainable patterns of some inner experiences found at the behavioral level, which significantly contradict the expectations of the individual, the culture to which he/ she belongs, these models being pervasive and inflexible. They are stable over time and occur in adolescence or early adulthood, and are responsible for the generation of stress and impairment (2). In terms of the model of cognitive-behavioral psychotherapy, personality disorders are associated with a dysfunctional pattern of thinking based and particularly influenced by dysfunctional beliefs/ cognitive schemas, manifested at the behavioral level by difficulty in adapting and in relationships (3) (4) (5). The central beliefs that occur in PD are specific patterns of thinking derived from the negative interaction of the patient and their genetic background with the disadvantaged physical environment in which the individual has evolved (6). Early maladaptive schemas (EMSs) are based on the dysfunctions that occur at one or more levels specific for attachment or development of the individual's own identity since childhood, and which occur in adulthood in a latent/ manifested way mainly in PDs,

being biologically determined (by temperament) (7) (8) (9) (10) (11) (12).

There are several strategies/ therapeutic guidelines that make up CBT, some representing new psychological methods, there already being empirical support that demonstrates effectiveness in the treatment of PDs (13) (14) (15). In terms of comorbidity between PD and a disorder from the non-psychotic psychiatric range, the result of the intervention CBT is as effective as in the case of the unique non-psychotic psychiatric one, especially in the case of co-occurrence between PDs and disorders of anxiety/ depression (16).

Clinically, PDs are worsening and maintaining factors of disorders from the field of psychopathology, but this depends on the specificity and intensity of the PD (17). The complexity of these cases required finding methods and techniques to complement the standard intervention intervention of CBT so that together with psychopharmacotherapy the clinical picture can be improved by the flexibility of maladaptive thinking schemas and the change of some maladaptive behaviors (18). THE INTEGRATIVE MODEL OF COGNITIVE-BEHAVIORAL THERAPY

Most cognitive theories are based on the assessment of the so-called “cold cognitions” (descriptions/ inferences – e.g. “They are glaring at me and want to hurt me”), namely, what a person thinks in a difficult life situation about that particular situation, and under that assumption negative feelings arise because of these cold cognitions. This is only a half-truth, since “hot cognitions” are actually responsible for generating negative emotions, more precisely the significance a patient attaches to “cold cognitions” (e.g. “I need to be appreciated by people and it is catastrophic if they want to hurt me”). Thus, if a patient with avoidant personality

1Lecturer, PhD, Clinical psychologist, CBT Psychotherapist, The Department of Ethics and Social Sciences, The University of Medicine and Pharmacy of Tîrgu Mureș, Romania.2PhD, MD, Senior in psychiatry, Mental Health Center of Tîrgu-Mureș, Romania.3Assistant professor, PhD student, MD, resident in psychiatry, The Department of Ethics and Social Sciences, The University of Medicine and Pharmacy of Tîrgu Mureș, Romania.4Lecturer, PhD, MD, Specialist in psychiatry, The Department of Psychiatry, The University of Medicine and Pharmacy of Tîrgu Mureș, Romania.Corresponding author: Tudor Nireștean, Assistant professor, PhD student, MD, University of Medicine and Pharmacy of Tîrgu Mureș, Str. Gheorghe Marinescu nr. 38, 540142, Tîrgu-Mureș, Romania, e-mail:Received January 29, 2016, Revised February 29, 2016, Accepted March 17, 2016

tudornirestean@gmail.com

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AbstractIn their entirety, personality disorders represent specific clinical nosologies which affect areas of the patient's functionality, especially in human relations. Cognitive-behavioral psychotherapy involves a number of guidelines/ strategies, most of them benefiting from a solid empirical support; thus, this paper deals with personality

disorders from the perspective of the general integrative model of CBT and not from the perspective of a specific therapeutic strategy.Keywords: cold cognitions, hot cognitions, cognitive restructuring, the ABCDE model, borderline personality disorder, narcissistic personality disorder

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disorder has an automatic negative thought in a social situation, such as: “others will laugh at me” (cold cognition), it is not the thought that causes anxiety but the significance that the person gives to the thought: “if they laugh at me, others will reject me and this is an unbearable and unacceptable thing” (hot cognition) (19) (20) (4). Both automatic negative thoughts (surface) and maladaptive cognitive schemas (depth) refer to/ include both hot and cold cognitions, which may occur in one of the two forms (1). The application of cognitive techniques combined with behavioral and relaxation one, but mainly the focus of the therapist on modifying hot cognitions, belonging to Cluster C in PD, will result in modification and flexibility of some dysfunctional beliefs, which contributes to remission of comorbidities and to the change of some maladaptive behaviors (21) (22). There are cases in which PDs have a unique, complex, and high intensity specificity (such as Borderline PDs) so that identifying and changing dysfunctional cognitions (hot cognitions) requires a completion through the use of experiential techniques. This is due to the fact that in severe personality disorders causality implies traumatic life events such as sexual/ emotional/ physical abuse in childhood (23) (24).

In the case of such PDs, a storage of traumatic memories in the amygdala is determined by a mechanism similar to posttraumatic stress syndrome, as well as a storage of cognitive traumatic memories in the hippocampus and neocortex (11), these being mediated by the prefrontal cortex. In such cases, CBT is effective on the one hand because of the inhibition of the response of the amygdala that generates negative emotions associated with trauma and which bypass the cognitive system and reasoning, and on the other hand because CBT boosts the response of the prefrontal cortex (PFC), cognitive restructuring having the purpose of alleviating dysfunctional cognitions related to trauma, since the activation of the dorsal prefrontal cortex (DPFC) causes a decrease in activation of the amygdala. This implicitly suggests that the cognitive conscious processes have a role in emotional regulation (25) (26) (27).

As a result, experiential, gestalt, mindfulness techniques and those which address the relationship of the object, cognitive-behaviorally conceptualized, may contribute to increased therapeutic efficacy in PDs, especially when the patient has a history of a trauma or psychotrauma in early childhood. The effectiveness of these techniques is given by the direct approach to early trauma using imagery and role-play, and by associated cognitive restructuring in order to increase the flexibility of dysfunctional beliefs with the aim of determining phenomena of awareness in these patients (28) (29). The resulting therapeutic benefits that stem from cognitive restructuring and awareness are essential in the process of changing maladaptive behaviors in PDs. Theory and, primarily, clinical practice indicates that, generally, PDs are egosyntonic, the patients are not aware of a multitude of reactions and maladaptive behaviors that they have in different life situations (30) (31). Due to this egosyntonic character, in terms of cognitive theory, we might consider that some of these types of behavior are determined by unconscious information processing (32). Identifying unconscious beliefs along with the conscious ones during the therapeutic process contributes to: 1) determining

cognitions/ beliefs/ dysfunctional cognitive schemas associated to specific PDs (33), 2) flexibilizing them through cognitive restructuring techniques, 3) the assumption of adaptive thought patterns (34).

In designing the treatment plan specific for CBT, the PD conceptualization of the case has to include a causal/ inter-determination relationship of the stressors such as negative life events (triggering stimuli) and maladaptive cognitive schemas of the patient (which also include biological vulnerability). This interdependence determines the cognitive, subjective/ emotional, and behavioral symptomatic manifestations in these patients (35).

Conceptualization in PDs is important because the patient thus understands the causes and manifestation manner of their psychological problems; this is essential in establishing the therapeutic goals together with the patient. Especially in PDs, a correct conceptualization is done after at least three sessions of clinical psychological evaluation. From a psychometric point of view, the most useful instrument to identify the PD is SCID-II, Structured Clinical Interview, the degree of validity of this instrument being directly proportionate to the therapist's clinical experience (21).

A model of conceptualization that can be applied simply and effectively in PDs (but also in other psychopathological disorders) is the ABC (DE) model. Hyland, and Boduszek (2012) citing Ellis (1958, 1962, 1994), David and Freeman (2015), David et al., (2010) have shown that the ABC model can describe psychopathology in that cognitions are considered determinants of emotional, behavioral, and attitudinal reactions of a patient. In other words, when a person relates themselves to negative life events (A) through a set of central irrational beliefs (cognitive B-schemas: “I value nothing as a human”) he/ she will generate surface dysfunctional beliefs (B-automatic thoughts: “I will not succeed”) which then support the dysfunctional negative emotions and maladaptive behaviors (C). Identifying these irrational beliefs/ central and surface dysfunctional thoughts and their debate/ change (D) contributes to replacing them with rational/ alternative beliefs, which clinically contributes to the remission of the disorder and adopting a style of thinking effectively and rationally (E) (1) (36) (19).

In PDs, this model must be completed and insisted on more, particularly on the relationship between B (beliefs) and C (consequences). Due to cognitive and dysfunctional behavioral patterns, it is necessary to complete the ABCDE model, where D (discussion/ modification) may be supplemented by cognitive diffusion techniques and E by changing the relational framework. Even if diffusion cognitive techniques appear to some extent in cognitive restructuring specific for traditional CBT (37), in the case of PDs they should be applied systematically. This is due, for example, to the thought-action fusion phenomenon that usually occurs in obsessive-compulsive disorder (OCD) (38), but also in several other PDs (31). Hence, a patient with comorbid OCD may think: what if I am going to hurt children? This thought (assessed by hot cognitions “I must not hurt them and it would be catastrophic if I harmed them”) triggers feelings of anxiety because for the patient thinking is synonymous with acting. Cognitive diffusion will focus

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on the separation of the thought of event/ the person itself, the way semantics can influence the development of dysfunctional negative emotions being already demonstrated (39) (40), the patient regarding it as a mental construct, stringing phrases, etc., that is, the patient is taught not to identify themselves with the thought or the thinking process.Also, another effective technique in these patients is framework changing/ relational context. With its aid, the patient with PD acquires coping adaptive mechanisms that help them learn to accept themselves as a person, to realize that thoughts are just thoughts, to live the present moment and to define the values of life, all of these being the attributes that belong to a psychological flexibility (41) (42).

Generating change in patients with PD is not achieved by using the therapeutic relationship as a framework for change, but by applying an ABC conceptual model in which the autobiography/ life history of the patient is brought to date “here and now” and faced with the current issue of the patient's life. For example, a patient with a narcissistic/ passive-aggressive PD can develop hostile behavior toward the therapist. In that particular moment, using the Socratic dialogue technique (asking questions the answer to which is mostly known by the therapist) the patient is asked “please let me know when, in your entire life, you have felt something identical, how you are feeling toward me/ behaving with me now (hostile feelings), or more precisely under what circumstances?” Reference to similar events in the history of life and reporting to the present with subsequent extrapolation through the same ABC model to a problem that is present in the patient's life makes them understand the source of their problems and thus generate change by changing irrational beliefs/ dysfunctional thoughts (43).

Another important aspect of CBT intervention in PDs will be based on the autobiographical versus semantic cognition model (19). Perhaps more than in any other psychiatric condition, in PDs cold/ hot cognitions affect autobiographical memory, which in turn changes the sense of semantic cognitions. For example, cold cognition in narcissistic PD: “I am special and others must respect me” is related to semantic memory and is interrelated with it. Thus, hot cognition is associated with semantic cognition and determines: “It is terrible and unbearable not to be respected” (as cited by David, 2003) (44). This dysfunctional type of thinking specific to PDs is determined by maladaptive cognitive schemas which, through the bio-psycho-social tendencies they incorporate, influence the behavioral and attitudinal patterns of the patient. Confronting these schemas in PDs can be done both in a cognitive way and through (experiential) imagery with the purpose to change some of the maladaptive behavioral patterns (45) (46) (47). Mindfulness techniques can also be used, but caution is advised in their implementation, particularly because of excessive detachment of the patient from life events, which prevents them to confront their own schemas due to decreased motivation (48).

Since behavioral techniques consist of exposure to the anxiogenic stimuli and behavioral experiments, they can be implemented by combining them with cognitive techniques, first by exposure in the psychotherapist's office (in-vitro), followed by gradual

exposure to real anxiogenic stimuli (in-vivo) (49) (50). CONCLUSIONS:CBT interventions in PDs require a holistic approach in which treatment involves customization depending on the particularities and specificities of the PD so that the therapeutic plan for these complex cases be based on a multimodal approach. The ABC model is defining both in terms of psychopathological conceptualization, and in terms of the therapeutic intervention itself, focusing on the application of a “bridge over time” in which the patient's past problems are brought to the present, the change thus being generated by modifying irrational beliefs “here and now”. It is necessary that the scientific support as known to date be supplemented with other studies that have immediate clinical application, this relieving the pathology associated to PDs and improving the relationing of these patients.ACKNOWLEDGEMENTS:We are thankful to Prof. Daniel David, Babeș-Bolyai University of Cluj-Napoca, Romania, associate professor at the Icahn School of Medicine at Mount Sinai, New York, USA, Research Director of the Albert Ellis Institute, New York, USA, for his supervision and the papers with which he provided us in writing this article.

REFERENCES1. David DO, Freeman A. Overview of Cognitive Behavioral Therapy of Personality Disorders. Beck AT, Davis DD, Freeman A (eds.). Cognitive Therapy of Personality Disorders. Third Edition, New York : Guilford Publications, 2015: 3-18.2. Association, American Psycyatric. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Wasington D.C.: American Psychiatric Association, 2013, 645.3. Clark DA, Beck AT. Cognitive theory and therapy of anxiety and depression: Convergence with neurobiological findings. Trend in cogn scien. 2010; 14: 418–424.4. Beck J. Psihoterapie Cognitivă. Cluj-Napoca : RTS, 2010, 19-21.5. Brad AA, Beck AT. Puterea integratoare a psihoterapiei cognitive. Bucureşti : Trei, 2011, 26-31.6. Beck AT. The Current State of Cognitive Therapy; A 40-Year Retrospective. Arch Gen Psychiatry. 2005; 62(9): 953-959.7. Leung PWL, Poon MWL. Dysfunctional Schemas and Cognitive Distortions in Psychopathology: A Test of the Specificity Hypothesis. J of Child Psycho and Psychia, 2001; 42(6): 755-765.8. Jovev M, Jackson HJ. Early Maladaptive schemas in Personality Disorders Individuals. Journ of Person Disord. 2004; 18(5): 467-478.9. Young, JE. Cognitive therapy for personality disorders: A schema-focused approach. Sarasota : Professional Resources Press, 1999.10. Young, JE, Brown G. Young Schema Questionnaire: Special Edition. New York : Schema Therapy Institute, 2001.11. Young J, Klosko, J, Weishaar M. Schema therapy : a practitioner's guide. New York : The Guilford Press, 2003, 26-27.12. Riso LP, McBride CA. Return to a Focus on Cognitive Schemas. In: Riso LP, et al. (eds.). Cognitive schemas and core beliefs in psychological problems: a scientist-practitioner Guide. Washington : American Psychological Association, 2007, 11.13. Kahl KG, Winter L, Schweiger U. The third wave of cognitive behavioural therapies: what is new and what is effective? Curr Opin Psychiatry. 2012; 25(6):522-8.14. Matusiewicz AK, et al. The Effectiveness of Cognitive Behavioral Therapy for Personality Disorders. Psychiatr Clin North Am. 2010; 33(3): 657–685.15. Hofmann SG, et al. The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses. Cognit Ther Res. 2012; 36(5): 427–440.16. Bédard M, Russell JJ, Myhr G. Impact of personality psychopathology on outcome in short-term cognitive-behavioral therapy for Axis I disorders., Psyc Resrc. 2015; 230(2): 524 - 530.17. Links PS, Eynan R. The relationship between personality disorders and Axis I psychopathology: deconstructing comorbidity. Annu Rev Clin Psychol. 2013; 9: 529-54.18. Farmer R, Chapman, A. Behavioral interventions in cognitive behavior therapy : practical guidance for putting theory into action, Washington DC: American Psychological Association, 2008, 177-203, 227-251.

Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu The Integrative Model Of Cognitive-behavioral Psychotherapy In Personality Disorders

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19. David D, Szentagotai A. Cognitions in cognitive-behavioral psychotherapies; toward an integrative model. Clinic Psycho Rev. 2006; 26: 284 – 298.20. David, D, Miclea M, Opre A. The information processing approach to the human mind: Basic and beyond. J. Clin. Psychol. 2003; 4: 353 – 369.21. Beck A, et al. Terapia cognitivă a tulburărilor de personalitate. Cluj-Napoca : ASCR, 2011, 36-48, 54.22. Livesley J. Integrated Treatment: A Conceptual Framework for an Evidence-Based Approach to the Treatment of Personality Disorder. Journ of Person Disord. 2012; 26(1): 17–42.23. Westphal M, et al. Borderline Personality Disorder, Exposure to Interpersonal Trauma, and Psychiatric Comorbidity in Urban Primary Care Patients. Psychi: Interpers and Biologic Process, 2013; 76(4): 365-380.24. Laporte L, Paris J, Guttman H, Russell J. Psychopathology, Childhood Trauma, and Personality Traits in Patients with Borderline Personality Disorder and Their Sisters. Jour of Person Disord. 2011; 25(4): 448-4.25. Yehuda R, LeDoux J. Response Variation following Trauma: A Translational Neuroscience Approach to Understanding PTSD. Neuron, 2007; 56(1): 19–32.26. Hofmann SG, Asmundson GJG, Beck AT. The Science of Cognitive Therapy. Behav Ther. 2013; 44: 199–212.27. Clark DA, Beck AT. Cognitive theory and therapy of anxiety and depression: Convergence with neurobiological findings. Trend in Cogni Scien. 2010; 14(9): 418–424.28. Arntz A, Weertman A. The influence of comorbid personality disorders on the outcome of CBT treatment of anxiety disorders. Europ. Psychia. 2007; 22(Supplem. 1):S16–S17.29. Edwards D, Arntz A. Schema Therapy in Historical Perspective. In: van Vreeswijk M, Broersen JNM (eds.). The Wiley-Blackwell Handbook of Schema Therapy, Chichester : John Wiley & Sons, Ltd., 2012, 4-26.30. Lăzarescu, M. Bazele psihopatologiei clinice. Bucureşti : Academiei Române, 2010, 170-181.31. Lăzărescu, M., and Nireştean, A. Tulburările de personalitate. Iaşi : Polirom, 2007, 195-201.32. David, D. Prelucrări inconştiente de informaţii. Bucureşti : Tritonic, 2004.33. Beck AT, et al. Dysfunctional beliefs discriminate personality disorders. Behav Resear and Ther. 2001; 39(10): 1213-1225.34. Beck AT, et al. Cognitive therapy for depression, New York : The Guilford Press, 1979.35. David, D. Tratat de psihoterapii cognitiv-comportamentale. a 2-a. Iași : Polirom, 2012, 131-144.36. Hyland P, Boduszek D. Resolving a difference between cognitive

therapy and rational emotive behaviour therapy: towards the development of an integrated CBT model of psychopathology. The Ment Heal Rev. 2012; 17(2): 104-116.37. David D, Hofmann SG. Another error of Descartes? Implication for the "Third Wave" Cognitive-Behavioral Therapy. J of Cognitiv and Behavio Psychothera, 2013; 13(1); 115-124.38. Lăzarescu, M., Ile, L. Tulburarea obsesiv-compulsivă:circumscriere, modele şi intervenţii. Iași : Polirom, 2009, 15-16.39. David D. E-Prime/R-Prime and emotion regulation in the context of the binary model of distress: an experimental investigation based on the general semantics framework. J of Cognit. Behav. Psychoter. 2013; Vol. 13(1):1-11.40. Blackladge, JT, Lillis, J. A avea un gând versus a te lăsa furat de un gând. In: Hayes S, Smith S (eds.). Noua terapie prin acceptare şi angajament, Iași: Polirom, 2013, 124-149.41. Levin ME, et al. The Impact of Treatment Components Suggested by the Psychological Flexibility Model: A Meta-Analysis of Laboratory-Based Component Studies. Behav. Therapy. 2012: 43(4): 741-756.42. David D, Mogoase C. Acceptance and commitment therapy's philosophical foundation under scrutiny: an In-depth discussion of A-ontology. Jounr. of E.B.P. 2015; Vol. 15(22): 169-177.43. David, D. http://albertellis.org/. Retrieved from Albert Ellis Institute: http://albertellis.org/rebt-in-the-context-of-modern-psychological-research/ , 2015.44. David D. Rational emotive behavior therapy; the view of a cognitive psychologist. W. Dryden (eds.) Theoretical developments in REBT. Hove: Brunner-Routledge, 2003, 130-160.45. Montgomery-Graham S. DBT and Schema Therapy for Borderline Personality Disorder: Mentalization as a Common Factor. J Contemp Psychother. 2016; 46: 53–60.46. ten Napel-Schutz MC, et al. Personality Disorder Patients' Perspectives on the Introduction of Imagery Within Schema Therapy: A Qualitative Study of Patients' Experiences. Cognitiv and Behavior Practice , 2011; 18: 482-490.47. Arntz A. Imagery Rescripting for Personality Disorders. Cognitiv and Behavior Practice. 2011; 18: 466-481.48. David D. Some Concerns About the Psychological Implications of Mindfulness: A Critical Analysis. J Rat-Emo Cognitive-Behav Ther. 2014; 32: 313–324.49. Beck, JS. Cognitive behavior therapy : basics and beyond. 2nd ed. New York : The Guilford Press, 2011, 256-277.50. Leahy R, et al. Cognitive Therapy for the Personality Disorders. Strack S. (eds) Handbook of personology and psychopathology. Chichester: John Wiley & Sons. 2005, 442-462.

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REVIEW ARTICLES

DEPRESSION SCREENING AT THE PRIMARY CARE LEVEL – A COST-EFFICIENT INTERVENTION

1 2Raluca Ileana Nica , Mihail Cristian Pîrlog

The prevalence of depression regardless of severity among the general population ranges between 8% and 12% (24, 25) depending on the methodological approach and scales used to classify depression, while the prevalence of major depression at the primary care level is 5-10% (23, 24, 32). Of the number of people presenting with depression in primary care, approximately 10-20% have a comorbidity with another non-communicable disease such as diabetes mellitus, cardiovascular disease, or cancer (23, 42). Given the high prevalence of depression and given that the patient first access the primary care services, as in most of countries, Romania being one of them, GP's are the main gatekeeper for a multitude of health problems, including mental health problems, and as they often have many tasks and a high caseload, they require easy to use, quick and effective screening tools that help them be confident in identifying depression and taking action on it. Depression screening usually implies the administration of questionnaires to people presenting with depressive symptoms by primary care staff (physicians or primary care nurses). Questionnaires can either be self-report or administered by a physician or nurse, having a small or medium number of questions the can be self-administered or can be administered by the family doctor both to the patients with high risk for developing depression such as

patients with chronic illness diagnosis (10, 36) but also to the other patients. One of the questionnaires that is frequently used by the primary care physicians to detect depression is patient health questionnaire 2 (PHQ - 2), that contain 2 questions namely: Over the last 2 weeks, how often have you been bothered by any of the following problems? 1.During the past month, have you often been bothered by feeling down, depressed, or hopeless? 2.During the past month, have you often been bothered by little interest or pleasure in doing things? The possible answers for each of questions are: Not at all (scoring 0), several days (scoring 1), several days (scoring 1), More than half the days (scoring 2) and Nearly every day (scoring 3). The total scoring ranges from 0 to 6, the authors (44) identified a PHQ-2 score of 3 as the optimal cut point of the screening purposes and stated that a cut point of 2 would enhance sensitivity and a cut point of 4 would enhance specificity. These two verbal questions have also the advantage that are concise and detect the majority of the depression cases (31). The purpose of the questionnaire is to enhance routine inquire about the most prevalent and treatable mental disorder in primary care. The National Institute for Health and Care Excellence (NICE) (15) recommended in the depression guideline that the entire population should be screened for depression at the primary care level, done with the PHQ -

1PhD Student, “Carol Davila” University of Medicine and Pharmacy Bucharest 2PhD, Lecturer at department of Psychiatry, University of Medicine and Pharmacy of CraiovaReceived February 26, 2016, Revised February 29, 2016, Accepted March 17, 2016

Abstract: Over 350 million people worldwide suffer from depression, and it is one of the leading causes of disability across the globe (1, 2, 3, 4, 5). In Europe, approximately 21 million people are affected by depression out of a population of 446 million people. Depression places a burden not only on individuals but also on the society due to its impact on health, social and economic systems. Depression accounts for 1% of the GDP of Europe (8), and amounted to approximately 118 billion euros, which translates to approximately EUR 253 per inhabitant (8). Given the magnitude of the burden of depression, there is a need for efforts to be directed at early identification to improve recovery and enhance treatment outcomes and ideally, to prevent depressive symptoms from developing into a clinical depressive episode. Depression is considered as a common mental health disorder (CMHD) given its high prevalence and many people presenting with depressive symptoms often seek care from their primary care physician or general practitioner first, making the general practitioner an ideal gatekeeper for screening and detection and management of depression (6, 7, 26). Screening for depression at the primary care level can have a significant impact on early recognition and

treatment, prevention of the development of more severe forms of depression, better adherence to treatment of chronic conditions, enhancement of recovery outcomes and consequently on the associated costs. According to the studies, despite the high prevalence of depression and the fact that many people experiencing depressive symptoms first come into contact with the health system through their primary care physicians, depression is in fact only identified in 30-50% of instances by primary care professionals (27,34). Early intervention is key as previous research shows that 20% of people who committed suicide visited a primary care physician in the month preceding the suicide (12, 35). The purpose of this review is to search based on the existing studies what are the recommendations regarding depression screening at the primary care level. At present, at the international level based on the existing studies is not a uniform opinion about recommending the screening at the primary care level for depression and about the criteria to be met for the depression screening at the primary care level that could lead to a cost-efficient intervention. It is still incipient the research regarding the efficiency of this intervention and the conditions in which it becomes cost-efficient.Key words: depression, screening, primary care

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2 questionnaire (15), which has a sensitivity of 97% (95% CI, 83% to 99%) and a specificity of 67% (95% CI, 62% to 72%) (31,43). A person responding yes to both of the PHQ-2 items is referred for a more in-depth assessment at the specialized level services. The probability rate for the screening to be positive when done with this two questions was 2.9 (2.5 to 3.4), and the probability rate for the screening to be negative was 0.05 (0.01 to 0.35) (31). At present, at the level of European and international clinical guidelines there is no agreement with regards to the efficiency of the depression screening at the primary care level (13,14,15,16,18,20,21,23,27,43,44). This is a consequence of the fact that there are not enough randomized control trials that could provide the necessary evidence regarding its efficiency when done at the general level of the population as well as when done for high-risk target groups. In addition, there is a concern regarding the unjustified increase of the number of patients that due to the false positives arising from tools, resulting in clients being sent to specialised care when in fact it is not required (27). On the other hand, studies of primary care patients have found that health care costs are higher in depressed patients than non-depressed in many categories, including primary care visits, medical specialty visits, lab tests, pharmacy costs, inpatient medical costs, and mental health visits (8, 9). To illustrate, one study conducted in England found that patients diagnosed with depression in Great Britain show that patients diagnosed with depression have costs two time higher ($4246 vs $2371, P < .001) compared with the ones that are not diagnosed, this situation remaining similar one year after the initiation of antidepressant treatment ($3971 vs $2644 (28). However, there is still a need to understand how big this problem is: is it more of a cost risk that more people get referred to specialized care when in fact they could be managed in primary care, or more of a problem if people go undetected completed in primary care which is more of an ethical and low quality of life problem. There are a number of aspects that should be taken into account when doing depression screening which could influence the result of screening and its cost-effectiveness. In order to recommend the screening as a cost-effective intervention at the primary care level there are some criteria which need to be met (23):1)Patients who do not have this diagnosis agree to do the screening (29)2)A relatively high number of positive results of screening are obtained (29)3)Agreement of patients who screen positively to access the specialized services for supplementary evaluation that would validate/invalidate the initial result4)Reasonable accessibility of the patients to the specialized services (33), patients from rural and isolated areas being disadvantaged5)A relatively high number of false positive results of screening are obtained (29)6)Patient agreement for depression treatment one the depression diagnosis was confirmed (29)7)For the treatment adherence psycho-education services are offered (37), knowing that there is an attrition rate from treatment of 70% in the first three months (38,39), while clinical guidelines recommend that depression treatment lasts between 6 months and one year (37)8)Accessibility to psychological interventions such as cognitive behavioural therapy (40,41), according to the

recommendation of the NICE clinical guidelines (15).An overview of the criteria listed above, leads to the conclusion that a screening program in order to be cost-effective has to take into consideration at least three essential aspects: a relatively high number of positive results of screening, a relatively low number of false positive results of screening and the accessibility to specialized services that can provide evaluation and comprehensive treatment (medication, psycho-education, cognitive behaviour psychotherapy) and a possibility for accomplishing these aspect is the integration of specialized services in primary care (20).As a consequence, it is important that randomized controlled trials focused on screening for depression at the primary care level specify the cri teria for inclusion/exclusion for screening, patients' randomization and the patients' accessibility of specialized services after getting a positive screening result. Some previous research studies have found that depressive symptoms do not change much as a result of screening done at the primary care level. To illustrate, a 2008 Cochrane systematic review (28) evaluated five randomized controlled trials and found that there is no evidence of a reduction of depressive symptomatology in the general population as a result of depression screening in primary care settings without substantial staff-assisted depression care supports. In another research study from the Netherlands depression screening was done on a sample of 1687 patients with a high risk of developing depressions through a questionnaire sent by mail. Out of the 770 patients that returned the questionnaire filled in, 226 (29%) showing a positive result for depression, only 17 (1%) initiated depression treatment (22). A research study done by a Spanish group of researchers (19,21), study that respected the randomization criterion and the cluster of patients screened consisted of patients with high risk for developing depression such as those with a depression history, those with somatic symptoms that are not caused by somatic illness and those with psychological comorbidities due to somatic illnesses and those with drug and alcohol abuse, the result showing that the depression rate 6 month after screening (15%) (21) was not different to the one in the control group (15,8%), (average mean difference − 0.02 and confidence interval 95%−0.25 la 0.20) (18). In contrast, the American clinical guideline for depression (46) reviewed 9 randomised controlled trials and concluded that screening for depression is cost-efficient in the context of integrated primary care and specialized services but inefficient in the absence of the services' integration (17,30). In sum, there seems to be mixed results supporting the notion of screening for depression at the primary care level. More research is needed for shading light on the efficiency of recommending the depression screening in the primary care services (11) and if this should be recommended to general population or only to indicated risk groups. Conclusions:At present there is insufficient evidence that universal screening for depression at the primary care level is beneficial from a cost-effectiveness or detection and treatment point of view. That being said, primary care professionals should still be aware of the following two groups of patients presenting in primary care that should be screened further for depressive symptoms:

Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

1.Group of patients with high risk of developing depression due to a previous diagnosis of depression, presence of a chronic illness, a family history of depression, unexplained somatic symptoms, traumatic life events and those that have a frequent utilization of services without a resulting diagnosis. 2.Patients who present with depressive symptoms such as little pleasure or interest in doing things, feeling hopeless, chronic fatigue or insomnia. The RCTs done up to now have inconclusive results with regards to the reduction of depressive symptoms and disappointing due to low percentage of people who accept to initiate the depression treatment, after being screened and diagnosed with depression at the primary care level.The absence of the research studies to demonstrate the cost-efficiency of universal screening for depression at the primary care level leads to the necessity that more research need to be developed in this direction, studies that should include more than the screening itself but also include the screening instruments, criteria for screening and treatment.

References:1.http://www.who.int/mediacentre/factsheets/fs369/en/2.http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.10015473.http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf4.http://www.sciencedirect.com/science/article/pii/S01406736126168945.http://www.sciencedirect.com/science/article/pii/S0140673613616116\6.http://www.bmj.com/content/347/bmj.f4913.long7.http://www.sciencedirect.com/science/article/pii/S187628591400432X

18.Sobocki P , Jönsson B, Angst J, Rehnberg C., Cost of depression in Europe, J Ment Health Policy Econ. 2006 Jun; 9(2):87-98.9.Rice D, Miller L. The Economic Burden of Affective Disorder. Br J Psychiatry. 1995; 166:34–42.10.Craven MA, Bland R. Depression in Primary Care: current and future challenges. Canadian Journal of Psychiatry 2013;58.8:442-8.11.Simon GE, Von Korff M. Recognition, management, and outcomes of depression in primary care. Arch Fam Med. 1995; 4(2):99-105.12.Luoma JB, Martin CE, Pearson JL. Contact with mental health and primary care providers before suicide: a review of the evidence. Am J Psychiatry. 2002; 159:909-916.13.US Preventive Services Task Force. Screening for depression in adults: US Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:784-92. 14.Pratt LA, Brody DJ. Depression in the United States household population, 2005–2006. NCHS Data Brief. 2008(7):1–8.15.National Collaborating Centre for Mental Health. Depression in adults with a chronic physical health problem: the NICE guideline on treatment and management. British Psychological Society, Royal College of Psychiatrists, 2010.16.Gilbody SD, Sheldon TD, House AD. Screening and case-finding instruments for depression: a meta-analysis. CMAJ 2008; 178:997-1003.17.Williams JW Jr, Mulrow CD, Kroenke K, Dhanda R, Badgett RG, Omori D, etal. Case-finding for depression in primary care: a randomized trial. Am J Med 1999; 106:36-43.18.Whooley MA, Stone B, Soghikian K. Randomized trial of case-finding for depression in elderly primary care patients. J Gen Intern Med 2000; 15:293-300.19.Romera I, Montejo AL, Aragones E, Arbesu JA, Iglesias-Garcia C, Lope S, et al. Systematic depression screening in high-risk patients attending primary care: a pragmatic cluster-randomized trial. BMC Psychiatry 2013; 13:83, 244X-13-83.20.Baas KD, Wittkampf KA, van Weert HC, Lucassen P, Huyser J, vanden Hoogen H,et al. Screening for depression in high-risk groups: prospective cohort study in general practice. Br J Psychiatry 2009; 194:

399-403.21.Brett D Thombs, Roy C Ziegelstein, Does depression screening improve depression outcomes in primary care? BMJ 2014; 348: g1253.22.Andrade L, Caraveo A. Epidemiology of major depressive episodes: Results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res. 2003; 12(1):3–21. doi:10.1002/mpr.138. 23.Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry. 2005; 62(6):593–602.24.Panzarino PJ Jr. The costs of depression: direct and indirect; treatment versus non treatment. J Clin Psychiatry. 1998; 59 Suppl 20:11-4. 25.Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, et al. Screening for Depression in Adults: A Summary of the Evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002; 136:765-776.26.Simon GE, VonKorff M, Barlow W., Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry. 1995 Oct; 52(10):850-6. 27.Thombs BD, Coyne JC, Cuijpers P, de Jonge P, Gilbody S, Ioannidis JP, et al. Rethinking recommendations for screening for depression in primary care. CMAJ 2012; 184:413-8.28.O'Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for depression in adult patients in primary care settings: a systematic evidence review. Ann Intern Med 2009; 151:793-803.29.Haden A, Campanini B, eds. The World Health Report 2001—Mental Health: New Understanding, New Hope. Geneva: World Health Organization; 2001:30.30.Strum R, Meredith LS, Wells KB. Provider choice and continuity for the treatment of depression. Med Care. 1996; 34:723-734.31.Health Services/Technology Assessment Text. Table 1: prevalence of depressive illness. In: Guide to Clinical Preventive Services, 3rd Edition: Recommendations and Systematic Evidence Reviews. Bethesda, Md: N a t i o n a l L i b r a r y o f M e d i c i n e . A v a i l a b l e a t : www.ncbi.nlm.nih.gov/books/ NBK235852/#adults. s21.32.Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry. 1992; 14:237-247.33.Pirkis J, Burgess P. Suicide and recency of health care contacts: a systematic review. Br J Psychiatry. 1998; 173: 462-474.34.Eisenberg L. Treating depression and anxiety in primary care: closing the gap between knowledge and practice. N Engl J Med. 1992; 326: 1080-1084.35.Melfi CA, Chawla AJ, Croghan TW, et al. The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression. Arch Gen Psychiatry. 1998; 55: 1128-1132.36.Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care. 1995; 33:67-74.37.Pomerantz JM, Finkelstein SN, Berndt ER, et al. Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis. J Clin Psychiatry. 2004; 65: 395-404.38.Pirraglia PA, Rosen AB, Hermann RC, et al. Cost-utility analysis studies of depression management: a systematic review. Am J Psychiatry. 2004; 161: 2155-2162.39.Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ. 2003; 327: 1144-1146.40.Lowe B, Kroenke K, Herzog W, Grafe K. Measuring depression outcome with a brief self-report instrument: sensitivity to change of the Patient Health Questionnaire (PHQ-9). J Affect Disorders 2004; 81:61-66. 41.Elkin I, Shea MT, Watkins JT, et al. Treatment of depression collaborative research program: general effectiveness of treatments. Arch Gen Psychiatry 1989; 46:971–82.42.http://www.emro.who.int/health-topics/depression/index.html43.Kroenke K., Spitzer RL, Williams JB. The Patient Health Questionnaire – 2: Validity of a Two Item Depression Screener. Medical Care 2003 (41) 1284-1294.44.http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/depression-in-adults-screening

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Raluca Ileana Nica, Mihail Cristian Pîrlog Depression Screening At The Primary Care Level – A Cost-efficient Intervention

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REVIEW ARTICLES

CLINICAL STUDY OF THE MENTATION, BEHAVIOR AND MOOD DISORDERS IN PARKINSON'S DISEASE

1 1 1 2Iordan Ganev , Toni Donchev , Krasimir Kostadinov , Velina Mancheva-Ganeva , 3 2 4 4Lachezar Manchev , Ivan Manchev , Mihai Pirlog , George L. Paraschiv ,

5 6Ruxandra C.M. Banu , Traian Purnichi

INTRODUCTIONParkinson's disease (PD) is a complex neurodegenerative condition manifested by characteristic motor impairment and a wide array of non-motor symptoms (NMS) (1, 2). Recently, sleep, fatigue, mood, cognition, pain and autonomic disorders have been recognized as important components of the disease, with a consistent impact on patients' health and quality of life (3, 4, 5, 6, 7). Despite of these problems and the high burden of NMS in most patients (4, 8) NMS remain frequently neglected (9) or undocumented (10). NMS thus present one of the biggest challenges for management by the clinician and a comprehensive assessment that includes NMS as well as motor state of the patient is essential (11). NMS can be assessed by several tools specifically designed for these symptoms, including the NMS questionnaire (NMSQuest)(12), the unified PD rating scale (UPDRS)(13) and the PD sleep scale (PDSS) (14). Pathophysiological, NMS may be related to both dopaminergic and non-dopaminergic alterations. For example, PET studies reported dopamine dysfunction at the hypothalamus (15). Degeneration of cholinergic,

adrenergic or serotoninergic pathways could also contribute to NMS genesis (16). Moreover, NMS can precede motor symptoms and thus PD diagnosis (17). Some studies suggest that NMS are common in all stages of PD and more common as the motor symptoms progression regardless of age of onset, levodopa dosage or disease duration. The most prevalent NMS in this study were highly similar to other previous international studies using the 30-item NMSQuest (18, 19 and 20). Non-motor symptoms dominate the clinical picture as PD progresses and may also contribute to shortened life expectancy (2, 21). Most do not respond to, and may be exacerbated by, dopamine replacement therapy (22). NMSs also account for the burden of hidden costs such as sick leave, early retirement and informal care not only for patients but also for caregivers in certain instances. The cost burden of NMSs is significantly high, especially in patients with advanced PD and increasingly severe symptoms, for which there is a poorer quality of life, reduced productivity and a greater need for health-care services, which in turn have an impact on direct and indirect costs. Thus, identifying disease-modifying treatments early in

1Clinic of Psychiatry, Military Medical Academy, 3 Sveti Georgi Sofiiski Street, 1606 Sofia, Bulgaria,Phone: +359898535610, E-mail: bestar@abv.bg 2Dep. of Neurology and Psychiatry, Trakia Faculty of Medicine, Stara Zagora, Bulgaria3Dep. of Physics, Biophysics, Roentgenology and Radiology,Faculty of Medicine, Stara Zagora, Bulgaria4University of Medicine in Craiova 5National Institute of Geriatrics and Gerontology of Bucharest6Alexandru Obregia Psychiatric Hospital in BucharestReceived November 19, 2015, Revised January 11, 2016, Accepted January 31, 2016

Abstract:Introduction: Parkinson's disease is a general invalidating neurodegenerative disease. The impaired non-motor functions are well recognized as part of the clinical course of the disease with great impact over the quality of life of the patients. On the other hand, they are highly unrecognized by clinicians and pose great difficulty in detection and measurement. The UPDRS is widely used to assess and follow up PD patients and Part I is used to assess non motor functions such as mentation, behavior and mood disorders. Therefore, we used it in our study for the assessment of the prevalence of the non-motor symptoms measured by UPDRS Part I in PD patients. Objective: To show that there's high prevalence of mentation, behavior and mood disorders as measured by UPDRS Part I in PD patients. Methods: 293 patients with Parkinson's disease (129 men and 164 women) aged 58-79, randomly picked for an 8-year period (2005-2012) were studied. The study used the following assessment tools: І. Unified Parkinson's Disease Rating Scale; Modified Hoehn and Yahr scale

for assessment of clinical symptoms; Schwab and England Activities of Daily Living Scale. Statistical methods for processing the data received – SPSS statistics software with analysis of variances and alternates was used. Results: The mentation, behavior and mood functions were studied in 293 patients diagnosed with Parkinson's disease. Lack of motivation/initiative was most frequently observed – in 245 patients (83.6%), followed by depression – in 200 patients (68.2%)and memory disorders – in 199 patients (67.9%). Thought disorder was the least frequent (26.9%). As a result of these disorders all patients had a considerably reduced quality of life mainly due to the development of significant cognitive impairment. Conclusion: This results confirm the observation that mentation, behavior and mood dysfunctions are a highly prevalent and important feature of PD. Therefore, treating physicians should look for them routinely. The UPDRS showed that it is sensitive and reliable tool for detecting such symptomatology.Key words: Parkinson's disease, depression, UPDRS, cognitive impairment

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the disease, before any functional or motor disability appears, is critical in reducing costs and preserving quality of life. Evidence suggests that initial therapy with non-levodopa agents is cost-effective, prolongs time to levodopa initiation and delays the onset of dyskinesia (23).There is a significant interrelationship of severity of disease, quality of life, patients and caregiver's burden, and cost of illness. NMSs contribute to the overall PD burden, which is a major determinant of quality of life. An increasing awareness of 'at-risk' individuals, based on detection of some or a combination of NMSs, is essential for an early identification of PD patients. Identification of prodromal patients plays a key factor in preventing the burden of economic costs and improving quality of life of patients and caregivers. Keeping this in mind, it becomes important to optimize the management of all aspects of NMSs in PD (24). Therefore we conducted our study to evaluate the high prevalence of non-motor symptoms in PD patients, particularly those measured by UPDRS Part I as it is one of the most used clinical scales in PD and thus with great clinical significance.OBJECTIVETo show the high prevalence of mentation, behavior and mood disorders as measured by UPDRS Part I in PD patients. MATERIAL AND METHOD293 out patients with PD (129 men and 164 women) aged 58-79, all retired due to illness (PD), randomly selected in terms of different PD stages for an 8-year period (2005-2012) were investigated after the inform consent was signed. They were outpatient recruited from a PD center of Department of Neurology and Psychiatry. The patients

received L-DOPA, dopamine agonists and antioxidants. The same team member who performed the clinical diagnosis also applied the scale. The patients have not been researched for concomitant illnesses. The study used the following assessment tools:І. Unified Parkinson's disease Rating Scale (UPDRS) -

. UPDRS is the most used scale to follow the longitudinal course of PD. (16, 17)ІІ. Modified Hoehn and Yahr scale for assessment of clinical symptoms;ІІІ. Schwab and England Activities of Daily Living Scale; Modified Hoehn and Yahr scale for assessment of clinical symptoms and Schwab and England Activities of Daily Living Scale are parts of UPDRS, but are mentioned separately because were used alone in the process of diagnosing the disease. The complete UPDRS was used latter for the measurement of the progression of the disease. IV. Statistical methods for processing the data received –SPSS 11 software with analysis of variances and alternates was used.RESULTSMENTATION, BEHAVIOR AND MOOD.1. Intellectual Impairment. That symptom was observed in 199 patients (67.9%). No significant gender-related differences were found. From Part 1 of UPDRS the item 1 - “light consistent forgetfulness with partial recollection of events” and the item 2 – “moderate memory loss with disorientation to time and often to place” were considerably prevalent as compared to the item 4 “severe memory loss with orientation only to person” (p<0.05%) (Table 1).

Part I: evaluation of mentation, behavior, and mood

Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev, Ivan Manchev, Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi Clinical Study Of The Mentation, Behavior And Mood Disorders In Parkinson's Disease

:

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2. Thought disorder. Thought disorder was found in 79

patients (26.9%). The item 2 - “benign hallucinations

“with retained insight was most frequently observed. The

item 3 – “Frequent hallucinations or delusions were

almost equally frequent. Then came the item 1 - “vivid

dreaming”, while persistent hallucinations and delusions

were the least frequent. No significant gender-related

differences were found (Table 2).

3. Depression (depression symptoms) the item 2 –

“sustained depression, lasting more than a week was the

most frequently observed in both genders. It was found in

90 patients (30.7%), followed by the item 1 – “periods of

sadness and guilt”. Their values increased significantly as

compared to the item “long-term depression with

vegetative symptoms and suicidal thoughts or intentions”

(p<0.05%) (Table 3).

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4. Motivation/Initiative. Lack of motivation and loss of initiative were most frequent among the PD patients. Those symptoms were found in 245 patients (83.6%). They were less assertive and more passive. Complete loss of motivation was the least frequent, the low results being statistically significant as compared to the milder impairment stages (p<0.01%) (Table 4). Apathy was observed in 54% of the patients diagnosed with mild to moderate PD related depressive symptomsCONCLUSIONS:This study showed moderate to high prevalence of non-motor neuropsychiatric disturbances in patients with PD in different stages of the disease as measured by the UPDRS Part I. This confirms that they are important part of the disease. Therefore, treating physicians should look for them routinely in their effort for the improvement of quality of life in patients with PD. The UPDRS showed that it is sensitive and reliable tool for detecting such symptomatology.DISCUSSIONS:As PD is a multidimensional disorder, the disease progression and treatment efficacy should be assessed not only through motor symptoms but also through psychopathological and autonomic symptoms. The Unified Parkinson's Disease Rating Scale (UPDRS) was developed as a brief, valid, and reliable scale for the assessment of activities and non-motor symptoms in PD and has replaced many of the older assessment scales. (25, 26) Cognitive disorders in PD consist first of an intellectual slowing and difficulties to organize and manage the intellectual capacities, with preservation of

global cognitive efficiency for long time.(27) Eventually, these disturbances can increase with the time and even progress to dementia. It is important to distinguish mild cognitive impairment from dementia, the latter being present only in a moderate percentage of PD patients. Our results revealed high prevalence of intellectual impairment (67.9%) as measured by the UPDRS which underlines the significance of its early recognition.Hallucinations occur usually in a normal state of consciousness, without delirium, and have a chronic course. (28) The prevalence of complex visual

hallucinations ranges from 22 to 38%.(29) Risk factors for hallucinations are older age, long duration of the disease, cognitive impairment, severity of PD symptoms, sleep disorders (somnolence), and visual disorders. (30) Risk of psychotic symptoms is increased in late onset PD, in patients taking high doses of dopaminergic drugs and suffering of REM sleep behavior disorder (RBD). Hallucinations must be identified by systematically questioning the patient. Visual hallucinations are surprising, but their intensity is quite variable. Benign hallucinations are limited to presence sensation, passing lights or visions at periphery of the visual field, with great tolerance by the patient. (31) Our results showed moderate frequency of thought disorder in our study population. Thought disorder was found in 79 patients (26.9%) and the item “benign hallucinations “with retained insight was most frequently observed.Depression occurs at any stage of the disease, even at the beginning or sometimes many years before the onset of the

disease. (32) Depression can occur in up to 27.6% of PD patients during early stages of the disease.(33) Depression may consist in major depressive disorder (17%), minor depressive disorder (22%), and dysthymia (13%), and clinical significant depressive symptoms are present in 35% of PD patients. (34, 35) Our results show that the item “sustained depression, lasting more than a week” was the most frequently observed in both genders. It was found in 90 patients (30.7%) in our study sample.Apathy consists in a loss of motivation, which appears in emotional, intellectual domains and in the behavior. For the diagnosis of apathy, the decrease of spontaneous acting must not be imputable to motor disability, nor to severe cognitive decline. (36, 37) Indeed, this neuropsychiatric symptom is frequent, with a prevalence of 30% to 40% in PD patients. (38, 39) Apathy is one of the

major determinants of a reduced quality of life in PD, (40) even at early stages. As such, early diagnosis and efficient therapy are important in order to avoid further consequences on quality of life and disability. Lack of motivation and loss of initiative were most frequent

Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

14

among the PD patients. Those symptoms were with high prevalence in our study sample and was found in 245 patients (83.6%).

ACKNOWLEDGEMENTS: All the authors had an equal contribution and have

similar rights. All the authors approved the final version of this article.DISCLOSURES:

The authors report no conflict of interest for this article.LIST OF ABBREVIATIONS:PD – Parkinson's diseaseUPDRS - Unified Parkinson's disease Rating Scale

MMSE - –MiniMental State Examination

МОСА - Montreal Cognitive Assessment Scale

MCI - Mild Cognitive Impairment

NMS – Non-motor symptoms

REFERENCES1.Lees AJ, Hardy J, Revesz T, et al. Parkinson's disease. Lancet 2009; 373:2055–2066.2.Chaudhuri KR, Healy D, Schapira AH et al. The non-motor symptoms of Parkinson's disease. Diagnosis and Management. Lancet Neurol 2006; 5:235–245. 3.Rahman S, Griffin HJ, Quinn NP et al. Quality of life in Parkinson's disease: the relative importance of the symptoms. Mov Disord 2008; 23:1428–1434.4.Barone P, Antonini A, Colosimo C et al. The PRI-AMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkin-son's disease. Mov Disord 2009; 24:1641–1649.5.Qin Z, Zhang L, and Sun F et al. Health related quality of life in early Parkinson's disease: impact of motor and non-motor symptoms, results from Chinese levodopa exposed cohort. Parkinsonism Relat Disord 2009; 15: 767–771.6.Li H, Zhang M, Chen L et al. Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson's disease. Mov Disord 2010; 25:2740–2746.7.Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM et al. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's dis-ease. Mov Disord 2011; 26:399–406. 8.Martinez-Martin P, Schapira AH, and Stocchi F et al. Prevalence of nonmotor symptoms in Parkinson's disease in an international setting: study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 2007; 22:1623–1629. 9. Shulman LM, Taback RL, Rabinstein AA et al. Non recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord 2002; 8:193–197. 10.Chaudhuri KR, Prieto-Jurcynska C, Naidu Y et al. The nondeclaration of nonmotor symptoms of Parkinson's disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord 2010; 25:697–701.11.Chaudhuri KR, Yates L, Martinez-Martin P. The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential. Curr Neurol Neurosci Rep 2005; 5:275–283. 12.Chaudhuri KR, Martinez-Martin P. Quantitation of non-motor symptoms in Parkinson’s Disease. Eur J. Neurol 2008;15(2):2-713.Fahn S, Elton RL and members of the UPDRS Developping commitee, “Unified Parkinson’s Disease rating scale”. In: Fahn S, Mardsen CD, Goldstein M (eds). Recent developments in Parkinson’s Disease. New York: McMillan, 1987, 153-16314.Chaudhuri KR, Pal S, DiMarco A et al. The Parkinson’s disease sleep scale: a new instrument for assesing sleep and nocturnal disability in Parkinson’s Disease. J Neurol Neurosurg Psychiatry 2002;73 (6): 629-63515.Chaudhuri KR. The dopaminergic basis of sleep dysfunction and nonmotor symptoms of Parkinson's disease: evidence from functional imaging. Exp Neurol 2009; 216 (2): 247-248

16.Barone P. Neurotransmission in Parkinson's disease: beyond dopamine. Eur J Neurol 2010; 17 (3): 364-37617.Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009; 8(5): 464-47418. Chaudhuri KR, Martinez-Martin P, Schapira AH et al. International multicenter pilot study of the first comprehensive self-completed non-motor symptomsQuestionnaire for Parkinson's disease: the NMSQuest study. Mov Disord 2006; 21:916-23.19. Crosiers D, Pickut B, Theuns J et al. Non-motorSymptoms in a Flanders-Belgian population of 215Parkinson's disease patients as assessed by the NonMotor Symptoms Questionnaire. Am J Neurodegener Dis 2012; 1:160-720. Gan J, Zhou M, Chen W, Liu Z. Non-motor symptoms in Chinese Parkinson's disease patients. J Clin Neurosci 2014; 21(5):751-4 21. Poewe W. The natural history of Parkinson's disease. J Neurol 2006; 253:VII2-VII6.22. Haycox A, Armand C, Murteira S et al. Cost effectiveness of rasagiline and ramipexole as treatment strategies in early Parkinson's disease in the UK setting: An economic Markov model evaluation. Drugs Aging 2009; 26:791-801.23. Chaudhuri KR, Martinez-Martin P, Antonini A. 2011; HIII (97): 15. ISBN 978-1-907673-23-8.24. Treves TA, Chandra V, Korczyn AD. Parkinson's and Alzheimer's diseases: epidemiological comparison. Descriptive aspects. Neuroepidemiology 1993; 12:336–344.25. Fran S, Elton RL, members of the UPDRS Developing Committee Unified Disease Parkinson's Disease Rating Scale. In: Fran S, Marsden CD, Calne DB et al. (eds). Recent Developments in Parkinson's disease. Florham Park, NJ: Macmillan Healthcare Information, 1987, 153-163.32. Movement Disorder Society Task Force on Rating Scales for Parkinson's disease. The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations. Movement Disord 2003; 18:738–50.33. Martinez-Martin P, Rodriguez-Blazquez C, Abe K et al. International study on the psychometric attributes of the Non-Motor Symptoms Scale in Parkinson disease. Neurology 2009; 73(19): 1584–1591.34. Dubois B, Pillon B. Cognitive deficits in Parkinson's disease. J Neurol 1997; 244(1): 2–8.35. Fénelon G, Mahieux F, Huon R et al. Hallucinations in Parkinson's disease. Prevalence, phenomenology and risk factors. Brain J 2000; 123:733–745.36. Fenelon G and Alves G. Epidemiology of psychosis in Parkinson's disease. J Neur Sci 2010; 289:12–17. 37. Diederich NJ, Goetz CG, Pappert EJ et al. Poor visual discrimination and visual hallucinations in Parkinson's disease. Clin Neuropharmacol 1998; 21:289–295.38. Tom T, Cummings JL. Depression in Parkinson's disease. Pharmacological characteristics and treatment. Drugs and Aging 1998; 12(1): 55–74.39. Ravina B, Camicioli R, Como PG et al. The impact of depressive symptoms in early Parkinson disease. Neurology 2007; 69(4): 342–347. 40. Reijnders JSAM, Ehrt U, Weber WEJ, Aarsland D, Leentjens AFG. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 2008; 23(2): 183–189. 41. Tan LCS. Mood disorders in Parkinson's disease. Parkinsonism Relat D 2012; 18(1): 74–76. 42. Marin RS. Apathy: a neuropsychiatric syndrome. J Neuropsych Clin N 1991; 3(3): 243–254. 43. Starkstein SE, Leentjens AFG. The nosological position of apathy in clinical practice,” J Neurol Neurosur Ps 2008; 79(10) 1088–1092.44. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsych Clin N 1992; 4(2): 134–139. 45. Sockeel P, Dujardin K, Devos D, Denève C, Destée A, Defebvre L. The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson's disease. J Neurol Neurosur Ps 2006; 77(5) 579–584.46. Benito-León J, Cubo E, Coronell C. Impact of apathy on health-related quality of life in recently diagnosed Parkinson's disease: the ANIMO study. Movement Disord 2012; 27(2):211–218.

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Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev, Ivan Manchev, Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi: Clinical Study Of The Mentation, Behavior And Mood Disorders In Parkinson's Disease

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ORIGINAL ARTICLES

EVOLUTION OF SYMPTOMATOLOGY AND FUNCTIONALITY OF ROMANIAN PATIENTS WITH MAJOR DEPRESSIVE EPISODE IN A COHORT OBSERVATIONAL STUDY

1Valentin P. Matei , Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, 3 3 5Lavinia Duica, Mihai Pirlog , George Paraschiv , Ioana G. Pavel, Alexandra Dolfi ,

5 5 5Diana A. Mihalache , Iulia A. Mitea, Diana Mihalcea , Mihnea Manea , 5 5 3 5 1Ana Giurgiuca , Mihai Bran , Bogdan Stania , Traian Purnichi , Dan Prelipceanu

1University of Medicine and Pharmacy “Carol Davila” Bucharest2University of Medicine “Ovidius” Constanța3University of Medicine in Craiova

Received December 3, 2015, Revised December 11, 2015, Accepted December 22, 2015

4University of Medicine “Lucian Blaga” Sibiu5MD at “Prof. Dr. Alex. Obregia” Psychiatric Hospital in Bucharest; email: tradress@yahoo.com; tel: 0040749156565

Abstract: Background: Depression is a common and disabling psychiatric condition which cause substantial impairment in daily functioning and increases the risk for both social and physical disability, and as a result, increases the costs for other medical services.Objectives: The study aims at underlining particularities regarding the evolution and functionality of patients with major depressive disorder (MDD) under Agomelatine treatment. The most important objectives were to evaluate the daily functionality in MDD patients under treatment, the evolution of the symptomatology and treatment adherence.Methods: We included in a prospective, observational and longitudinal study 1194 patients with depressive episode, who were assessed with Clinical Global Impressions Scale (CGI scale) and Quick Inventory of Depressive Symptomatology Scale (QUIDS-C16), in order to perform a correlational analysis. Results: In this study, the target group had a moderate symptomatology (depressed mood, loss of concentration, anhedonia) and had a good evolution from the second week of treatment and a considerable improvement of anhedonia after 10 weeks of treatment.Conclusions: The antidepressant treatment with Agomelatine was considered efficient and safe, with an important improvement of the symptomatology after 10 weeks of treatment, a good treatment adherence and improvement in daily functioning.Key words: CGI scale, anhedonia, antidepressant treatment.

Rezumat:Istoric: Depresia este o frecventă tulburare psihică care determină modificări substanțiale în funcționarea de zi cu zi, crește riscul pentru handicap social și fizic, și secundar, cresc costurile și pentru alte servicii medicale.Obiective: Studiul a avut ca scop evaluarea particularități lor evoluției simptomatologiei , funcționalitatea si aderența terapeutică la pacienții cu tulburare depresivă majoră sub tratament cu agomelatină.Metode: Am inclus într-un studiu prospectiv, observațional și longitudinal 1194 pacienți cu episod depresiv sau tulburare depresivă majoră, care au fost evaluați prin Scala de Impresie Clinică Globală (scala CGI) și Inventarul Rapid al Simptomatologiei Depresive (QIDS-C16), în scopul de a realiza o analiză statistică elocventă.Rezultate: In acest studiu, grupul de pacienți înrolați au avut o simptomatologie moderată (dispozitie depresivă, scaderea capacității de concentrare, anhedonie) și au prezentat o evoluție bună incă din a doua săptămână de tratament și o îmbunătățire considerabilă a anhedoniei după 10 săptămâni de tratament.Concluzii: Tratamentul antidepresiv cu agomelatină a fost considerat eficient și sigur, iar după perioada de 10 săptămani de tratament s-a constatat o îmbunătățire importantă a simptomatologiei, o bună aderență la tratament și îmbunătățirea funcționării socio-ocupaționale zilnice.Cuvinte cheie: scala CGI, anhedonie, tratament antidepresiv

1. INTRODUCTIONMajor Depressive Disorder (MDD) is a

heterogeneous, complex and debilitating disorder that put a burden not only upon patients but also on their family and society (1). MDD considerably affects patient's daily functionality with important effect on their quality of life because the social functionality decreases as depression's severity increases. The literature data are showing that almost 52% of patients with Major Depressive Episode

(MDE) have persistent and important symptomatology compared to 18% of patients with mild MDE that experience major difficulties in daily social interactions (2).

Even if the available antidepressants (AD) help patients to obtain a good response or remission of symptoms, there is a period of several weeks until their entire pharmacological action is perceived by patients and clinicians.

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Even so many patients have inadequate response, comorbid symptoms that are not completely controlled or under a poly-pharmacotherapy that can be associated with tolerability issues (1).

There are still significant controversies regarding the moment when the symptomatic amelioration became significant on the evolution of MDE treated with AD. Even though several methodological limitations exist (like the focusing on the clinical response rather than upon symptomatology remission), the results collected from randomized clinical trials (RCT), meta-analyses and observational studies show that: (A). in general AD are associated with early amelioration of the symptoms which can be observed in the first 2 weeks since antidepressant

treatment initiation (defined as a reduction ≥ 20% in depression severity measured by standardized rating scales); (B) several antidepressants like Agomelatine are associated with early amelioration of both central symptomatology (depressed mood and anhedonia) and specific symptoms like sleep-wake disturbances; (C) early amelioration is a predictor of symptomatology remission and early response. Subsequently, the lack of amelioration could be seen as a predictor of nonresponse (3).

According to analytical studies on factors and groups there has been shown that depressive mood (negative emotions), anhedonia and psychomotor symptoms are the elements that define major depressive disorders the best (4). Diverse studies showed that anhedonia can precede the onset of a depressive episode, it can influence its severity, can be a predictor of a bad outcome 12 months later and it is a residual symptom frequently present. The inclusion of patients in subtypes according to the type of symptoms and phenomenological approach could constitute a further step of the future psychopharmacology in order to prescribe the best antidepressant according to specific symptoms. There are articles on this subject in the literature but until now the results are not yet conclusive (5). 2. METHODS2.1 Participants

The study population was constituted of in and outpatients from 59 representative centers in Romania. The investigators were psychiatrists working in the public health system (hospital or specialized ambulatory) or in private practice. The observational study took place

st thbetween 1 of February 2012 and 8 of June 2012.In the study were included 1194 patients with a first

MDE or a recurrent MDE according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) [6], over 18 years old but under 75 years, whose doctors recommended Agomelatine before the inclusion in the study and who accepted in common agreement with their clinician to be monitored during study. In the final analysis we also included patients with bipolar disorder (2.68%, n=32) and patients without specification of MDE (10%, n=125) due to the fact that this was a naturalistic study and these diagnostics were modified after baseline.

Out of 1194 MDE patients included in the study, more than half (645 patients) were with recurrent MDE. The exclusion criteria referred to the patients that: (A) went to the doctor in emergency regime, (B) use of

psychoactive substances, (C) have an age under 18 years or above 75 years old and (D) presented serious comorbidities and/or severe pathology which could affect their participation in the study (hepatic impairment, limited cooperation, legal limited capacity, another severe non-psychiatric disorder, cancer, medication abuse, severe cardiovascular disease or renal failure).

The main objective of this observational study was the evaluation of daily functionality in MDD patients under AD treatment, who were prospectively followed. The secondary objectives included MDE severity improvement and MDD symptomatology evolution in thesepatients and the adherence to the AD treatment.

The prospective observation of the patients lasted for 10 weeks and included 4 visits: V0- baseline, V1- 2 weeks since inclusion, V2 and V3 at 6 respectively 10 weeks since inclusion. At the initial visit (baseline) depress ive mood , anhedon ia and focus ing difficulties/decision making were the most prominent symptoms as measured with Quick Inventory of Depressive Symptomatology scale.2.2 Instruments

In order to evaluate the MDE standard instruments were used: CGI scale (Clinical Global Impressions Scale). The CGI scale is an instrument through which the clinician evaluates 3 different global parameters (7):

A. The severity of the disease: global evaluation of actual severity of patient's symptoms (CGI-S);

B. The global improvement: general comparison between patient's actual state and the initial (baseline) state (CGI-I)

C. Efficacy index: general comparison between patient's initial state and a rapport between the actual therapeutic benefit and severity of adverse reactions (CGI-E).For severity evaluation of MDE Quick Inventory of Depressive Symptomatology scale (QIDS-C - Rush et 16

al., 2003) was used. The QIDS scale includes all the 16

symptomatology domains, which was developed on the base of DSM-IV criteria for diagnosis of major depressive episode [8,9]: 4 items for evaluation of sleep disturbances; 2 items for evaluation of psychomotor disturbances (agitation or slowing of the psychomotor function); 4 for appetite/ weight evaluation (increasing/decreasing of appetite and weight gain/loss) and only one item for evaluating the other 6 domains (depressed mood, low interest, decreased level of energy, feelings of inutility/ guilt, concentration/decision making difficulties, suicidal ideation). Each item is evaluated on a scale from 0 to 3. For the domains that require the evaluation of least 2 items, the highest score is considered. For example if at the beginning of sleep the value of insomnia is 0, the value of insomnia the middle of the night sleep is 1, for morning insomnia is 3 and 0 for hypersomnia, then the sleep disturbances domain gains a total score of 4 points. The total score varies between 0 and 27. The reference interval in the evaluation of symptoms severity is the 7 days period prior to evaluation. QIDS is sensitive to the change of the clinical state status associated with medical treatment, psychotherapy or somatic treatment, being a very good instrument in both research and clinical practice.

Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog, George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea, Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu Evolution Of Symptomatology And Functionality Of Romanian Patients With Major Depressive Episode In A Cohort Observational Study

:

17

The degree of adherence to the treatment throughout study development was evaluated by the number of pills declared by the patient as taken from one visit to another. study was prospective, observational and longitudinal; all the participants signed an inform consent before being included into the study.2.3 The statistical analysis was done by CEGEDIM Company using Kynos Modalisa software with a confidence level of 95%, a maximum sampling error for all patients of ± 2.81% and p-value.

Table 1 – Statistical parameters

3. RESULTS3.1. Demographic characteristics:Women represented 68% of the population (n=1190) with a mean age of 48 years. A higher representation had the patients included in the 55 to 60 years' age group (18%), followed by patients in the 50 to 55 age group (17%) (n=1186). The lowest representation in the group was for the patients under 25 years (3%). No gender differences were seen regarding the type of episode and the duration of anterior affliction in patients with a current major depressive episode. The characteristics of the study group are presented in Table 2.3.2. QIDS-C score and symptoms evolution: The average 16

of QIDS-C score at inclusion was 12.25. This is 16

associated with medium intensity symptoms. The symptoms were ameliorated by the AD treatment reaching a final score of 1.77 at V3 (the interval 0-5 is considered in normal range). The symptoms evolution was statistically significant between visits and also at the final visit (Table

3). The evolution of the symptoms severity at each evaluation (comparing to the initial moment) is graphically presented in Figure 1.

* n=1186-1189 for each domain evaluated with QIDS-C16

Table 2: Baseline characteristics of the MDD patients

Figure 1: Evolution of the MDE severity during study (QIDS-C scale)16

Table 3: Evolution of the MDE symptoms evaluated with QIDS-C scale16

Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

LEVEL OFANALYSES

- All CRFs - Splits on patient

categories, e.g.gender, agecategories,

- diagnosis INDICATORS - Absolute and relative

frequencies forcategorical variable

- Central tendencyindicators forquantitative variables

- Confidence levelsprovided in annex (Excel file)

SIGNIFICANCE TESTING

- Fisher’s F test – testing for significant differences among pre-defined groups

- z-test for means, t-test for matched samples – testing for significant differences between visits

- Chi2 test – testing for association among pre-defined groups

OPEN-ENDED QUESTIONS

- Similar answers grouped in categories

- Database keeps the original verbatim as well

Characteristics % of all patients Women 68

Diagnosis

Major depression-new episode

46.56

Major depression-first episode

40.28

Bipolar disorder 2.68

Unspecified 10.46

Prior antidepressant treatment Yes 46%

No 54%

Total medium score QDIS-C16*

12.25

Dominant symptoms (QDIS-C16):

Depressive mood

Sad mood more than half the time

56

Sad mood almost every time 35

Involvement, interest to other people or activities

Keeps just one or two activities of the past ones

51

There is no interest regarding past activities

22

Focusing, decision making

Tries most of the time to focus attention or make decisions

61

Cannot focus well enough to read or cannot take even minor decisions

19

12,25

8,41

4,501,77

0

5

10

15

20

25

V 0 V 1 V 2 V 3

QIDS-C16 score

Visit Average QIDS-C16value

t-value (vs V0)

p-value

Visit 0 12,25 [12.05-12.45] - -

Visit 1 8,41 [8.21-8.61] 46,08 0,00

Visit 2 4,5 [4.33-4.67] 80,19 0,00

Visit 3 1,77 [1.66-1.88] 96,72 0,00

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Table 4: The evolution of the depressed mood, anhedonia and impaired concentration/ making decisions during the study (QIDS-C )16

Figure 2: The evolution of the highest score symptomatology on QIDS-C scale16

Table 5: Z test applied on the QIDS-C items16

The statistics revealed that while all the patients presented a significant improvement of the symptomatology, some categories have registered more progress, as follows (supplementary details can be obtained on request): ·Age: The elderly patients (age between 65 and 75) have a slower improvement than other age categories, for all the visits (p=0.002 at V1, p=0.001 at V2 and V3);·Major depressive episode (new/recurrent): it has been noted significant differences between the patients with a new major depressive episode and recurrent in all that concerns the total scores (ANOVA), but the items scores (Chi2). The patients with recurrent MDD had a slowly recovery.3.3. Comorbidities of the MDD on the patients of the study:The presence of somatic comorbidity was observed in 26% of the patients; the most frequently reported comorbidities (n=307) were arterial hypertension (82%) and the ischemic coronary disease (30%).3.4. Adherence to treatment during the study:From the patients who had previous AD treatment (n=645, 54%), the main reason for switching/discontinuing was the loss of therapeutic response, followed by the patients' choice not to be treated with that AD or considering that he does not need treatment anymore. Though, there are cases for which this reason could not be specified.

Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog, George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea, Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu: Evolution Of Symptomatology And Functionality Of Romanian Patients With Major Depressive Episode In A Cohort Observational Study

QIDS-C16 Items

Patient Percentage V0 (W0) N=1186 - 1189

V1 (W2) N=1187- 1190

V2 (W6) N=1181 - 1184

V3 (W10) N=1169 - 1171

Depressive mood Doesn’t feel sad

0.2 7 24 67

Feels sad in less than half of time

8 47 65 32

Sad mood more than half of time

56 43 11 1

Sad moodalmost all the time

35 3 1 0.1

Implication No changefrom thecommon level of interesttoward other people oractivities

1 9 36 76

Decreasing the interest ofcurrent activities

26 52 56 23

Keeping only 1 or 2 activities from the old ones

51 35 8 2

Having nointerest from the oldactivities

22 4 0.1 0

Concentration/ making decisions No change in the dailycapacity ofconcentration and making decisions

1 7 25 60

Sometimes feels undecided or observe that attention isdiminished

20 49 65 39

Most part of the time trying to concentrate or makingdecisions

61 40 9 2

Cannot concentrating enough forreading orcannot making minor decisions

19 4 0.4 0

35%

19% 18%

3%

22%18%

9%7%

4% 4%

0,3%

4% 3% 2%1%0,4% 0,3%

0,2%0,1% 0,1% 0,2%

0,1% 0% 0% 0% 0% 0% 0%

V 0

V 1

V 2

V 3

Item Visit 1

vs 0

Visit 2

vs 0

Visit 3

vs 0

Depressed mood 17.9 24.7 25,3

Concentration/making

decisions

12.0 16.1 16.1

Self-esteem 11.0 15.7 15.7

Suicidal thoughts 5.0 5.2 5.2

Implication 13.4 18.0 18.0

Energy level/fatigue 12.1 16.0 16.0

Psycho-motor

retardation

8.0 10.7 10.7

Z value > 2.56 is meaningful for the interval of

confidence about 99%

19

At the end of the study98.5% of the patients (n-1194) continued the AD treatment (7 patients discontinued the treatment due to economic reasons).During the observational study there have not been reported any adverse reactions linked to Agomelatine according to the investigators clinical judgement.

4. DISCUSSIONSWe noticed a concordance of the results of this

study with the data from the literature regarding the percent of women with MDD and the low prevalence of depression in the age category under 25 years (2).

The group of patients enrolled in this study had a moderate symptomatology and this could be explained by the fact that patients who were addressing to the emergency services were excluded. Another explanation could be the presence of the residual symptoms in patients with recurrent depression and their treatment was changed because of the loss of therapeutic response (the main reason of the changing anterior treatment in this study).

For this group of patients, the symptomatology domains at the initial moments and who had a considerable improvement starting with the second week of treatment have been represented by the depressed mood, loss of concentration and making decisions and anhedonia. Of the three domains, after ten weeks of

rdtreatment anhedonia presented a better improvement. (3 table). Considering that the medication for the study was represented exclusively by Agomelatine, it is possible that this substance plays an important role which can concord with the results of the recent studies (4, 10).

In this study, the patients recently diagnosed (<3months) and treated have presented a significant improvement after ten weeks of treatment compared with the patients diagnosed with depression more than one year before. Also, the patients with more than 65 years old diagnosed with depression more than one year before had a slow improvement during all the visits. These two observations sustain the importance of recognizing depression and the initiation of the treatment from the beginning, which allow a good improvement of the functionality.

Considering that the medication was based almost exclusively on Agomelatine, the results of the study can be considered representative for this substance. In the same time, we cannot make specific correlations, the Chi test being extremely sensitive in big samples. Another limit can be represented by the short period of the study – 10 weeks, which can permit an observation of the evolution and the adherence only for the acute phase of the treatment. It was observed a good improvement of the functionality from the self-reported data by the patients. At the same time, it might be useful to make a correlation of the functionality with the symptomatology through the evaluation of the patient's response at a self-administered scale for functionality.

5. CONCLUSIONSThe AD treatment with considered efficient and

A good adherence to the treatment is a great contributor to the improvement of the symptomatology and thus, to recovering the level of functionality before the disease episode. No side effects related to the AD treatment were recorded according to the clinician's judgement.

the MDE patients. After 10 weeks of treatment it has been noticed a good improvement of MDE patients' symptomatology, a good adherence to treatment and a good improvement of the functionality from the self-reported data by the patients.6. DISCLOSURE

The authors declare that received in the past grants from Servier Pharma and other speaker fees. In addition, all the authors received in the past speaker's fees and/or sponsorship from Servier Pharma and others companies for scientific research or communication. Dr. Traian Purnichi also works as a marketing specialist consultant for Servier Pharma and Dr. George Paraschiv and Iulia-Alma Mitea are employees of Servier Pharma. 7. ACKNOWLEDGEMETS

All the authors had an equal contribution and have similar rights. All the authors approved the final version of this article.The authors will like to thank:-Cegedim Company that did the statistical analysis using a Kynos Modalisa software.-MedinteractivPlus for helping on the study draft. - Servier Pharma for offering the grant that made this study possible. - The following doctors for assessing the patients included in this study: Ramona Baba, , Alexandrina Baloescu, Ciprian Bacila Magdalena Blaj, RuxandraBloj, Mihaela Brad, Magdalena Bujor, Ion Burlacu, IeronimBurghelea, Ana Campeanu, Liliana Chelariu, Angela Chelcea, RaisaCirlig, Victor Cojocaru, Delia Coltoiu, MinodoraDumitrescu, Corina-Mihaela Echim, LiviuGanea, Felicia Giurgi, Carmen Haragus, AncutaHordoan, CameliaHriban, Ioana Ilea, Sorin Iova, Bogdana Lazar, MinodoraManea, Auras Margina, LigiaMincu, Eli Morman, Eugenia ElzaMoruzzi, Eduard Motoescu, Ildiko Must, VioricaNancu, Laura Pacurar-Catana, Corina Panzaru, Ioana Papava, Rita Platona, Alina Pop, Cristian Popa, NeoniliaPopa, Elena Preda, Dan Prelipceanu, Eugenia Roca, Dan Rusu, HoratiuSalvan, Iulia Daria Scorei, Daniela Sichitiu, Lia Sonia Simon, Adina Singalevici, Rodica Stan, Luigya-Claudia Stanci, JeniStanciu, Izabela Stania, AncaTalasman, Livia Taran, Andreea Teodorescu, AlexandruTiugan, Mihaela Tranca, Silvia Trandafir, Corina Tudor, Monica Varlan, Claudiu Ionut Vasile, AndreiaVasilescu, Nicolae Vlad.

8. FINANCIAL SUPORTThis study was founded by a grant from Servier Pharma.

REFERENCES1.Bodinat C. de, Guardiala-Lemaitre B., Mocaer E., Renard P., Munoz C., Millan MJ.: Agomelatine, the first melatonergic antidepressant: discovery, characterization and development, Nature Reviews, Vol 9, August 2010, 628-6422.Lam R.W., Mok H.: Depression, Oxford University Press, New York, 20083.Lam R.W.: Onset, time course and trajectories of improvement with antidepressants, European Neuropsychopharmacology (2012) 22, S492 – S4984.Giannantonio M., Martinotti G.: Anhedonia and major depression: the role of agomelatine, European Neuropsychopharmacology (2012) 22, S505 – S510 5.Hasler G., Drevets WC., Manji HK., Charney DS., Discovering endophenotypes for major depression, Neuropsycjopharmacology (2004), 29, 1765 – 17816.APA, Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. American Psychiatry Association Press, Washington DC. Text revision. 2000

Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

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List of abbreviations:

1. CGI scale - Clinical Global Impressions Scale2. QUIDS - Quick Inventory of Depressive Symptomatology Scale3. MDD - Major Depressive disorder4. MDE - Major Depressive Episode5. AD - Antidepressant6. RCT - Randomized Clinical Trials7. DSM-IV-TR - Diagnostic and Statistical Manual of Mental Disorders

Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog, George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea, Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu: Evolution Of Symptomatology And Functionality Of Romanian Patients With Major Depressive Episode In A Cohort Observational Study

ORIGINAL ARTICLES

MENTAL DISORDERS IN CHILD EPILEPSY

1 2 3Elisabeta Racos – Szabo , Iringó Száva , Anamaria Todoran – Butila

1Senior lecturer, University of Medicine and Pharmacy Tg-Mures, Clinic of Pediatric Neurology and Psychiatry, Tg-Mures, Panselutelor 5., tel.0365-882662, elisabetaracos@yahoo.com2Resident Physician Pediatric Psychiatry, Clinic of Pediatric Neurology and Psychiatry Tg-Mures, Tg-Mures, Panselutelor 5, 3Junior Lecturer, University of Medicine and Pharmacy Tg-Mures - Subject Medical Genetics:, Specialist Physician Pediatric NeurologyReceived November 1, 2015, Revised November 16, 2015, Accepted January 8, 2016

AbstractIntroductionEpilepsy is a chronic condition characterized by the presence of recurrent paroxysmal brain seizures (epileptic seizures), as a result of an excessive discharge of neurons. The prevalence of mental disorders in epilepsy is of 30-40%, and those of psychoses of 1-3%, being higher in patients with temporal lobe epilepsy. Psychoses and personality disorders are 3 times more frequent in those with temporal lobe seizures. Among the mental disorders in child epilepsy we care to mention: cognitive impairment, behaviour disorders with aggressiveness and psychomotor agitation, learning disorders, depression, anxiety.Material and methodsThere have been evaluated 24 children with epilepsy, admitted in 2014 in the Clinic of Pediatric Neurology and Psychiatry Tg-Mures, with ages between 12 and 18. There have been applied Raven's Matrices, various scales for depression and anxiety (MASC, Hamilton, Beck, Bender). The diagnosis of mental disorders has been established based on the criteria DSM-V and ICD 10. ResultsThe prevalence of mental disorders in child epilepsy was of 12%, with the highest incidence in the group age between 10 and 12. These mental disorders have been: cognitive disorders (79%), behaviour disorders (37,5%), disharmonic personality developments (33%), anxiety (20,8%), psychosis (8,3%), depression (4,2%).DiscussionsChild epilepsy evolves having a high risk for the occurrence of cognitive impairment, behaviour disorders, language or mood disorders all the more so as the underlying structural disorders are higher. The early onset of the epileptic seizures under the age of 3, in a child with a psychic under development represents a vulnerability factor. Patients with temporal lobe epilepsy present a risk for psychoses, also 1/3 of the epileptics develop personality disorders.ConclusionsThe onset of epileptic seizures under the age of 3 constitutes a risk factor for the occurrence of language disorders, cognitive or behaviour disorders.The prognostic in mental disorders in the epileptic child is influenced by the underlying structural brain anomalies responsible for the occurrence of epileptic seizures. Key words : epilepsy, mental disorders, child.

RezumatIntroducereEpilepsia este o afectiune cronica caracterizata prin prezenta crizelor cerebrale paroxistice recurente (crize epileptice),ca urmare unei descarcari excesive a neuronilor .Prevalenta tulburarilor psihice in epilepsie este de 30-40%,iar cea a psihozelor de 1-3%,fiind mai mare la pacientii cu epilepsie de lob temporal.Psihozele si tulburarile de personalitate sunt de 3 ori mai frecvente la cei cu crize de lob temporal.Dintre tulburarile psihice in epilepsia copilului amintim:deficitul cognitiv,tulburarile de comportament cu agresivitate si agitatie psiho-motorie,tulburarile de invatare,depresia,anxietatea.Material si metodeAu fost evaluati 24 copii cu epilepsie, internati in 2014 in Clinica de Neurologie si Psihiatrie pediatrica Tg-Mures,avind virsta cuprinsa intre 12 si 18 ani.S-au aplicat matricea Raven,diferite scale pentru depresie si anxietate(MASC, Hamilton,Beck,Bender).Diagnosticul tulburarilor psihice s-a stabilit pe baza criteriilor DSM-V si ICD 10.RezultatePrevalenta tulburarilor psihice in epilepsie a fost de 0,14%,cu incidenta cea mai mare la grupa de virsta intre 10 si 12 ani(33%).Acestea au fost: tulburari c o g n i t i v e ( 8 3 % ) , t u l b u r a r i d e comportament(37,5%),dezvoltari dizarmonice de personalitate(33%),anxietatea(20,8%),psihoza(8,3%),depresia(4,2%).DiscutiiEpilepsia copilului evolueaza cu risc crescut de aparitie a deficitului cognitiv,a tulburarilor de comportament, a celor de limbaj sau de dispozitie cu atit mai mult cu cit tulburarile structurale subiacente sunt mai mari.Debutul precoce al crizelor epileptice sub virsta de 3 ani, la un copil cu un psihic in dezvoltare reprezinta un factor de vulnerabilitate.Pacientii cu epilepsie de lob temporal perzinta risc pentru psihoze, de asemenea 1/3 dintre epileptici dezvolta tulburari de personalitate.ConcluziiDebutul crizelor epileptice sub virsta de 3 ani constitue factor de risc pentru aparitia tulburarilor de limbaj,a celor cognitive sau de comportament.Prognosticul in tulburarile psihice la copilul epileptic este influentat de anomaliile structurale cerebrale subiacente responsabile de aparitia crizelor epileptice. Cuvinte cheie : epilepsie,tulburari psihice,copil.

21

22

Introduction

Epilepsy is a chronic condition characterized by the presence of recurrent paroxysmal brain seizures (epileptic seizure), as a result of an excessive discharge of the neurons within a structural or biochemical epileptogenic brain injuries (according to the International League Against Epilepsy approved by World Health Organization).(1,2) The association of epilepsy with mental disorders is already known from antiquity(8). Later Kraepelin affirmed that patients with epilepsy present personality disorders and predisposition for psychoses.(9)The prevalence of mental disorders in epilepsy is of 30-40%, being able to exceed even 60% in those with different neurological impairments, and the psychoses one is of 1-3%, being higher in patients with temporal lobe epilepsy(5,7). Kaplan mentions that epileptics present mental disorders, depression being present in 7.5 up to 34% of them. At the same it is to be mentioned that psychoses and personality disorders are 3 times more frequent in patients with complex partial seizures. (9) The most frequent comorbidity in epilepsy is depression, the estimated prevalence of it vary between 50-55% in patients attending hospital, or ambulatory system, 20-30% in those with reccurent seizures, and 6-9% in those in remission. Depression can appear after epilepsy surgery too.(4) The suicide rate in population suffering of epilepsy is 5% (in the whole population 1,4%).(11) The epilepsy treatment can also lead to depression, nervousness, abnormal thinking (Topiramate, vigabatrin) (4,6).The mental disorders in the epileptic child are different depending on age(10). Thus, we care to mention behaviour disorders with instability and psychomotor agitation, cognitive impairment, personality disorders (with viscosity, aggressiveness, irritability, egocentrism), learning disorders, attention deficit, hyperactivity disorder, anxiety, depression, psychosis. (12)

Material and methods

A study has been performed within the Clinic of Pediatric Neurology and Psychiatry from Tg-Mures during 2014, being monitored 24 children with various forms of epilepsy, aged between 10 and 18, who presented neurological disorder as well. The patients have been examined neurologically, paraclinically by EEG, brain imaging (CT scan and brain MRI), also psychiatrically by Raven's Matrices, projective tests, depression and anxiety scales (MASC, Hamilton, Beck, Bender).

Results

Out of the 171 cases of epilepsy diagnosed in our Clinic of Pediatric Neurology and Psychiatry from Tg-Mures in 2014, the prevalence of epilepsy associated with mental disorders was of 12%.The specialized literature mentions a higher incidence of epilepsy in male gender, in the studied cases this being of 71%.The maximum incidence of mental disorders in epileptic children has been in the group with ages between 10 and 12, namely 33% (6 cases), 12-14 years old 29% (7 patients), 14-16 years old 25% (6 patients), 16-18 years

old 13% (3 patients).

Figure 1: Mental disorders prevalence in child epilepsy

Figure 2 : Distribution of cases on genders

Figure 3 : Distribution of cases on age groups

Figure 4 : Incidence of mental disorders in child epilepsy

The incidence of mental disorders in epileptic children according to their background has been equal between the

Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila Mental Disorders In Child Epilepsy:

23

urban and rural environment, namely 50%.The mental disorders encountered in the child diagnosed and treated for epilepsy have been:- cognitive disorders: (37%);- behaviour disorders: (17%)- disharmonic personality developments: (15%)- attention deficit hyperactivity disorder: ( 9%)- anxiety: ( 9%)- learning disorders: (7%)- psychosis: (4%)- mood disorders of depressive nature: (2%)

Behaviour disorders have been encountered in 11 patients consisting in irascibility (2 cases), disobedience and stubbornness (4 cases), auto- and hetero-aggressive manifestations (5 cases).

Figure 5: Incidence of behavior disorders in child epilepsy

Personality disorders have been encountered in 8 cases, consisting in withdrawal (1 case), viscosity (1 case), impulsiveness (4 cases), antisocial manifestations as theft and consumption of alcohol (2 cases).

Figure 6: Incidence of personality disorders in child epilepsy

The psychotic type of disorder has been the most severe mental disorder in the epileptic child, consisting in mystical and paranoid delirious ideas, in 2 cases (8%).Language disorders were also present consisting in dyslalia, stuttering, dysarthria in 13 children. Also there have been encountered affective and mood disorders namely: 1 case of depressive disorder, and also 1 case of anxiety.The associated cognitive impairment in the children patients with epilepsy under treatment, has consisted in mild mental retardation (intellectual disability) with

schooling in aided school in 25% of cases, moderate mental retardation in 17% of cases and severe mental retardation in 37% of cases, and 21 % of the patients had a normal cognitive level.

Figure 7: Incidence of psychotic disorder, of learning and mood disorders in child epilepsy

Figure 8 : Incidence of cognitive impairment in child epilepsy

The severity of the cognitive impairment has been correlated with the age at the epilepsy onset, thus in 45.8% of cases the onset of the epileptic seizures has occurred before the age of 3.17% of the epileptic children have not been schooled, due to the seizures frequency and lack of favourable response to the antiepileptic treatment, at the same time due to the associated cognitive impairment.

DiscussionsRecent studies point out the fact that child epilepsy evolves with a high risk for the occurrence of cognitive impairment, behaviour disorders, emotional disorders, language or mood disorders. This risk is all the more higher as the structural underlying disorders to the epileptic process are more pregnant(2). The monitored patients presented a cognitive impairment in most of the cases (79%), only 21 % of them having a normal cognitive level. At the same time the behavioural disorder consisting in disobedience, irascibility, impulsiveness with auto- and hetero-aggressiveness has been present in 11 patients.(12) In most of the epileptic children within the study (45.8%) the onset of the epileptic seizures occurred before the age of 3, when the child's psychic is at its peak of development, therefore the psychic vulnerability is higher, aspect mentioned also in the specialized literature (1,2,6)Personality disorders appear in a 1/3 of the epileptic

Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

24

patients , fact emphasized also in the children within the study, namely in 33% of them, under the form of viscosity, adhesiveness, antisocial type of elements, instability, impulsiveness, consistent with the specialized literature data.(9,12)It is mentioned the occurrence of psychosis in patients with temporal lobe seizures (5). Epileptic children with psychotic decompensation within our study (2 cases) have presented seizures of complex absence type, complex focal seizures secondarily generalized, the structural lesion being in the temporal lobe.(5,7)Some of the antiepileptic medications may cause reactions of behavioral or cognitive type (12). Within the study performed it could not be established if cognitive or behavioral disorders had a bearing on the antiepileptic medication treatment.(6)

Conclusions

Among the mental disorders in epileptic children, the most frequently emphasized was the cognitive impairment (79%).The maximum incidence of mental disorders was in the age group between 10 and 12.The early onset of epileptic seizures under the age of 3 constitutes an unfavourable prognostic factor for the occurrence of mental disorders as language disorders,

cognitive impairment, behavioral disorders.The prognostic of mental disorders in child epilepsy is influenced by brain structural anomalies responsible for the epileptic seizures, also the therapeutic response at specialized medication.

Bibliography1. Popescu V, Arion C., Dragomir D.: Convulsions and epilepsy in child, Medicala Publishing, Bucharest, 1989, 298-301.2. Benga I: Epilepsy and non-epileptic seizures, Medical University Publishing „Iuliu Hatieganu”, Cluj-Napoca, 2003, 271-275.3. Kaplan HI:Synopsis of Psychiatry, Seventh Edition, Williams and Wilkins, Baltimore, 1994.4. M J Jackson1,D Turkington2: Depression and anxiety in epilepsy, N e u r o l N e u r o s u r g P s y c h i a t r y 2 0 0 5 ; 7 6 : i 4 5 - i 4 7 doi:10.1136/jnnp.2004.0604675. Trimble MR, Schmitz B: Schizophrenia and other psychoses, in Aicardi J: Epilepsy: a comprehensive text book, 2007, 204:2113-216. Rogozea R, Magureanu S, Constantin D: Updates in epilepsy, Tehnica Publishing, Bucharest, 1998, 108-1107. Sander JW: Epilepsy, Questions and answers, 20008. Popescu V: Pediatric neurology, Teora Publishing, 2001, 619-622, 627-634, 893-9009. Dome L: Szemelyiseg zavarok, Filum Publishing, 200110. David A.S, Fleminger S,: Lishman's Organic Psychiatry, Wiley-Blackwell, 2009, 333-35411. Barnhill I, Hurley A: Mood disorders and epilepsy, Ment. Health Aspects Dev. Disabil., 2003, 6:36-39.12. Leung LS, Mc Lachan RS: Behaviours induced or disrupted by complex partial seizures, Neurosciences and behaviour reviews, 2000, 24:762-775.

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Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila: Mental Disorders In Child Epilepsy

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25

A submitted manuscript will be acknowledged and assigned a manuscript number, which is to be used in all further correspondence. Manuscripts are reviewed and given a priority based on their originality, importance of the findings, scientific merit and significance for the field, interest to readers, lucidity, and suitability for publication. Manuscripts with insufficient priority for publication are rejected promptly. Other manuscripts are sent to expert consultants for peer review. The existence of a manuscript under review is not revealed to anyone other than peer reviewers and editorial staff. Peer reviewers remain anonymous and are expected to maintain strict confidentiality. After the review process has been completed, authors will be informed by mail of the Editor's decision.

Corrections

Scientific fraud is rare events; however, they have a very serious impact on the integrity of the scientific community. If the Editorial Board uncovers possible evidence of such problems it will first contact the corresponding author in complete confidence, to allow adequate clarification of the situation. If the results of such interactions are not satisfactory, the Board will contact the appropriate official(s) in the institution(s) from which the manuscript originated. It is then left to the institution(s) in question to pursue the matter appropriately. Depending on the circumstances, the Romanian Journal of Psychiatry may also opt to publish errata, corrigenda, or retractions.

Manuscript Preparation

Manuscript organization

1. First page should include: Article title: titles should be short, specific, and descriptive, emphasizing the main point of the article. Avoid a 2-

part title, if at all possible. Do not number the title, e.g., I or Part I. Do not make a declarative statement in the title. Title length, including punctuation and spaces, ideally should be under 100 characters and must not exceed 150 characters.

2. Second page: a) Author(s). First name, middle initials and surname of the authors, without any scientific, didactic or

military degrees; (e.g., Mircea A Birţ, Aura Vaida, not Birţ M.A., Vaida A.). b) Footnote that specifies the authors' scientific titles, the name and the address of their workplaces

(institution and department) for each author; contact details of the corresponding author (full address, telephone number, fax number, e-mail address) and the address of the institution and department where the study has been carried out. Contact details will be published unless otherwise requested by the author.

3. Third page: a) Abstracts should have no more than 300 words. For original articles they should consist of five

paragraphs, labeled Background, Objective(s), Method(s), Result(s), and Conclusion(s).b) Keywords maximum of 6 keywords (minimum of 3), according to Index medicus. Keywords should not

repeat the title of the manuscript.4. Fourth page and next:

• Original papers organized in:a) Introduction (no more than 25% of the text), material and methods, results, comments or discussions and

Romanian authors should send both the Romanian and English version of the article, including title, abstract and key words. Foreign authors should send the English version of the article.

Manuscripts must be prepared in conformity to the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication” issued by the International Committee of Medical Journal Editors (www.icmje.org).

Articles must be written in Microsoft Word, Style: Normal + Justify, Font: Times New Roman, size 12. All manuscripts must be typed double-spaced. Original source files, not PDF files, are required. In text editing, authors should not use spacing with spacebar, tab or paragraph mark, but use the indentation and spacing options in Format -> Paragraph. Automatic paging is preferred.

Subheadings of the article should be left-justified, typed with capital letters, Font: Times New Roman, size 12.The abstracts and Key words must be written in Microsoft Word, Style: Normal + Justify, Font: Times New Roman,

size 11, italics. Figures must be cited in order in the text using Arabic numerals, (e.g., fig.2). Their width should be 6,5cm (in order

to fit in a column) or 13,5 cm (in order to fit in both columns). The figures have to satisfy the following conditions:- black and white photographs with good contrast, with recommended sizes;- scanned photograph with a resolution of 300 dpi and subsequently edited on a computer, original file (*TIF,

*JPG);- illustrations (drawings, charts) created on a computer, cited in the text, original file (*XLS, *CDR).Every figure should be accompanied by a title and a legend.Tables, numbered consecutively with arabic numerals, should have a width of 6,5 cm or 13,5 cm. Every table

should be also accompanied by a title and a legend. The distribution of tables and figures in the text should be balanced.

Please do not import tables or figures into the text document, but only specify their insertion in text (e.g., Table No.3

insertion). They have to be sent in separate files. Files should be labeled with appropriate and descriptive file names.

26

Instructions for authors

acknowledgements. b) Material and methods have to be described in enough detail to permit reproduction by other teams. The

same product names should be used throughout the text (with the brand name in parenthesis at the first use).

c) Results should be presented concisely. Tables and figures should not duplicate text. d) The discussions should set the results in context and set forth the major conclusions of the authors.

Information from the Introduction or Results should not be repeated unless necessary for clarity. The discussion should also include a comparison among the obtained results and other studies from the literature, with explanations or hypothesis on the observed differences, comments on the importance of the study and the actual status of the investigated subject, unsolved problems, questions to be answered in the future.

e) In addition to the customary recognition of non-authors who have been helpful to the work described, the acknowledgements section must disclose any substantive conflicts of interest.

f) Abbreviations shall be preceded by the full term at their first apparition in text. A list of all used abbreviations shall be made at the end of the article.

g) Separate pages: tables, graphics, pictures and schemes will appear on separate pages.• References should be numbered consecutively in the order in which they are first mentioned in the text. Identify

references in text, tables, and legends by Arabic numerals in parentheses.- The reference list will include only the references cited in the text (identified by Arabic numerals in

parentheses, not in square brackets and not bold).- All authors should be listed when six or less; when seven or more, list only the first three and add 'et al'

(Ionescu I, Popescu I, Georegscu I et al).- The name of the Journals cited in the References should be abbreviated according to ISI Journal Title

Abbreviations.

Examples:

INSTRUCTIONS FOR MANUSCRIPTS SUBMITTED IN ELECTRONIC FORMAT

VERY IMPORTANT: All manuscripts intended for publication will be subject to peer-review by a committee of experts which assesses the scientific and statistical correctness of articles submitted. The committee receives the manuscripts without knowing the authors' name and proposes possible changes, which will be transmitted to the authors by the medium of Editorial Board. The authors have the obligation to oversee the text in English language with the help of a professional translator.

- Reference to a journal publication: Vraşti R, Matei VMI. The crisis centre in Romania. Eur J Psychiat 2002; 29:305-311.Reynolds CF, Frank E, Perel JM et al. Treatment of consecutive episodes of major depression in the elderly. Am J

Psychiat 1994; 151(12):1740-3.- Reference to a book:

Vrasti R. The crisis centre in psychiatry. Toronto, London: Academic Press, 1993, 26-52.- Reference to a chapter in an edited book:

Schuckit MA. Alcohol-Related Disorders. In: Sadock BJ, Sadock VA, Ruiz P (eds). Comprehensive Textbook of Psychiatry. Philadelphia: Lippincott Williams and Wilkins, 2009, 1268-1287.

The placement of the italics, punctuation and the general aspect of the text format must comply with the rules mentioned above. This is a mandatory and eliminatory condition.

The text should be edited in “Word for Windows”.1. Use as few formatting commands as possible:- input your text continuously (without breaks);- do not use different types of fonts to highlight your text;- any word or phrase that you would like to emphasize should be indicated throughout the text by underlining;- use only the “Enter” key to indicate the end of the end of paragraphs, headings, lists etc.;- do not use the “Space Bar” to indicate paragraphs, but only the “Tab” key.2. Charts and tables should be edited in Word or Excel. Please indicate in the text, the place of the table, specifying

its name.3. You can scan photographs (using Photostyler, Adobe-Photoshop or any other compatible programs) and save

them as .tif or .jpg files. Please indicate in the text, the place of the photograph, specifying its name.4. You may use a common compression program: ARJ, RAR or ZIP.5. Make sure that the text file from CD and the print-out correspond exactly. 6. Make sure that there are no errors on your CD.7. Make sure your CD is adequately packed.8. Make sure your CD has no viruses.

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Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016

Address to send the manuscripts is:

REVISTA ROMÂNĂ DE PSIHIATRIEASOCIAŢIA ROMÂNĂ DE PSIHIATRIE ŞI PSIHOTERAPIEProf. Dr. Dan PRELIPCEANUClinical Hospital of Psychiatry “Prof. Dr. Alexandru Obregia”Şos. Berceni 10, sector 4, 041914 BucureştiTel./Fax: +40-21-334.84.06E-mail:

Contact: Viorel Roman – web editorE-mail: Tel. +40-21-334.84.06

- print edition - online edition

aliat@artelecom.net

aliat@artelecom.net

www.e-psihiatrie.ro/revistawww.romjpsychiat.ro

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Instructions for authors

ROMANIAN JOURNAL

OF PSYCHIATRY

APR

CONTENTS

i 2

SPECIAL ARTICLES

& o a i i 1

& o i 4

& a a 8

& o ai 11

ORIGINAL ARTICLES

&

15

&

INSTRUCTIONS FOR AUTHORS 25

Romanian Journal of Psychiatry and Psychotherapy is recognized in Romanian National Council for Scientific Research in Higher Education, starting with January 2010, at B+ category

Romanian Journal of Psychiatry and Psychotherapy is indexed in the international data base Index

Copernicus – Journal Master List, starting with 2009. Ż

Doctors subscribed to this journal receive 5 CME credits / year. Scientific articles published in the journal are credited with 80 CME credits / article.

The Spiritual Dimension f Personality nd ts Role n Mental HealthAurel Nireștean, Emese Lukacs, Gabriela Buicu, Monica Bilcă,

Pokorny Vasile

The Integrative Model f Cognitive-behavioral Psychotherapy n Personality Disorders

Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu

Depression Screening t The Primary Care Level – Cost-efficient Intervention

Raluca Ileana Nica, Mihail Cristian Pîrlog

Clinical Study f The Mentation, Behavior nd Mood Disorders n Parkinson's Disease

Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva- Ganeva, Lachezar Manchev, Ivan Manchev, Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi

Evolution of Symptomatology and Functionality of Romanian Patients with Major Depressive Episode in a Cohort Observational Study

Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog, George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea, Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu

Mental Disorders n Child Epilepsy 1Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila

REVIEW ARTICLES

Ż

www.romjpsychiat.ro

EDITOR-IN-CHIEF: Dan PRELIPCEANUCO-EDITORS: Dragoş MARINESCU Aurel NIREŞTEAN

ASSOCIATE EDITORS:Doina COZMANLiana DEHELEANMarieta GABOŞ GRECUMaria LADEACristinel ŞTEFĂNESCUCătălina TUDOSE

Executive editors: Elena CĂLINESCU Valentin MATEI

STEERING COMMITTEE:Vasile CHIRIŢĂ (Honorary Member of the Romanian Academy of Medical Sciences, Iaşi)Michael DAVIDSON (Professor, Sackler

School of Medicine Tel Aviv Univ., Mount Sinai School of Medicine, New York)

Virgil ENĂTESCU (Member of the Romanian Academy of Medical Sciences, Satu

Mare) Ioana MICLUŢIA (UMF Cluj-Napoca)Şerban IONESCU (Paris VIII Universiy, Trois-

Rivieres University, Quebec)Mircea LĂZĂRESCU (Honorary Member of the

Romanian Academy of Medical Sciences, Timişoara)Juan E. MEZZICH (Professor of Psychiatry

and Director, Division of Psychiatric Epidemiology and International Center for Mental Health, Mount Sinai School of Medicine, New York University)

Sorin RIGA (senior researcher)

Eliot SOREL (George Washington University, Washington DC)

Maria GRIGOROIU-ŞERBĂNESCU (senior researcher)

Tudor UDRIŞTOIU (UMF Craiova)

Teodor T. POSTOLACHE, MD (Director, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore)

Dan RUJESCU (Head of Psychiatric Genomics and Neurobiologyand of Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munchen)