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Neurobiology of Dynamic Psychotherapy

An Integration Possible?

manuela Mundo

bstract

In the

last decades, Kandel's innovative experiments

have

demonstrated

that brain structures and synaptic connections are dynamic. Synapses can be

modified by a wide variety of environmental factors, including leaming and

memory processes.

The

hypothesis that dynamic psycho therapy process involves

mem ory and leaming procesess has opened the possibility of

a

dialogue between

neuroscience and psychoanalysis and related psychotherapy techniques.

The primary aim of the present article is to critically review the more recent

data on neurobiological effects of dynamic psychotherapy in psychiatric disor-

ders. Relevant literature ha s been selected using the databases currently avail-

able online (i.e., PubM ed). The literature search has been limited to the past 10

years and to genetic, molecular biology, and ne uroimaging studies that have ad-

dressed the issue of changes induced by psychotherapy. Most of the genetic

studies on mental disorde rs have dem onstrated that psychiatric conditions re-

sult from a complex interaction of genetic susceptibility and en vironm ental ef-

fects. For none of the many psychiatric conditions investigated has a purely

genetic background been found. Molecular biology s tudies have indicated that

gene expression is influenced by several environm ental factors, including early

experiences, traum as, leam ing, and mem ory processes. Neuroim aging studies

(using fMRI an d PET) hav e found that not only cognitive but also dynam ic psy-

chotherapy has measurab le effects on the brain. In addition, psychotherapy m ay

modify brain function and metabolism in specific brain areas. Most of these

studies have considered patients with major depressive disorders and com-

pared the effects of psyc hothe rapy with the effect of stan dard p harm aco therapy.

In conclusion, recent results from neuroscience studies have suggested that dy-

namic psychotherapy h as a significant impact on brain function a nd metabo lism

in specific brain areas. The possible ap plications a nd developm ents of this new

area of research toward the conceptualization of an integrative approach to

treatment of psychiatric disorders are discussed.

In a pu re neuroscientif ic perspective, Kand el with his studies on m o-

lecular biology of memory and leaming using animal models gave us a

Emanuela M undo, M.D., Dept. Of Psychiatry, Dept. Of Clinical Sciences Luigi Sacco,

University of Milan, Milan, Italy.

The autho r thanks: Claudio M ontresor, M.D., for stimula ting the research in the field

of

neurobiology of dynamic psychotherapy and for helping in the literature search; Alvise

Orlandini, M.D., for the insightful comments on the first draft of the article; and Joan

Tolchin, M.D., for the constant supp ort in the preparation of the m anuscript and for the

precious revisions provided.

Journal of

The

American Academy of Psychoanalysis and Dynamic Psychiafry,

34 4)

679-691,

2006

©

2006

The American Academy of Psychoanalysis and Dynamic Psychiafry



680 MUNDO

potential key to unders tand the neurobiology of the psy chotherapy-in-

duced process of change and a precious connection between psychologi-

cal and biological processes. In the pap er Genes, nerve cells, and the re-

mem brance of things past (Kandel, 1989) the author hypothesized that

since psychotherapy resembles leaming, structural changes in the brain

tha t are seen with learriing experiences will be also detectable by im aging

methods in subjects who underwent psychotherapy. The interest in the

possibility of integration between djmamic psychiatry and neuroscience

rather than an opposition of the two models of viewing mind and brain

functioning, has been extensively addressed in two subsequent pivotal

papers by Eric Kandel published in The merican Journal o Psychiatry in

1998 and 1999 (Kandel, 1998,1999). In these papers the author discusses

how new know ledge in the biology and plasticity of the central nervous

system may influence our understanding of what happens during dy-

namic psychotherapies. In addition, the author aims to describe the points

of intersection and dialog ue between psychoanalysis and neuroscience

in order to give a more scientific foundation to psychoanalysis

itself

Several areas of possible intersection between psychoanalysis and biol-

ogy have been identified. The natu re and the neurobiological s tructures

involved in the unconscious men tal processes, the na ture of psychological

causality, the relationship between psychological causality and

psychopathology, the role of early experiences in predisposing to

psychiatric disorders, and the structural brain changes that may occur

dur ing psychotherapy are examples of this possible integration.

The aim of

the

present article is to critically review the literatu re of the

past 1 years addressin g the issue of neurob iological aspects of dyn am ic

psychotherapy effects. Relevant literature has been selected using the

databases currently available online (i.e., PubMed). The literature

search has been lim ited to the pas t 10 years (January 1995 to December

2005). Basically, there are three area s of neuroscience that ha ve contrib-

uted to the unders tand ing of the biological equivalents of change pro-

cess induced by dyn amic p sychothe rapy: genetics, molecular biology,

and neuroimaging.

CLINIC L CH R CTERISTICS OF THE CH NGE PROCESS

IND UC ED BY DYN M IC PSYCHOTHER PY

A dialogue between dynamic psychiatry and neuroscience should

start from the understanding of what are the clinical correlates and

mechanisms underlying the change process induced by dynamic psy-

chotherapy. The changes induced in the patient by dynamic psychother-

apy have been widely observed and studied from different perspectives.

According to the Boston Process of Change Study Group (1998) the



NEUROBIOLOGY OF DYNAMIC PSYCHOTHERAPY 681

changes that occur during the psychotherapy process appear to belong

to the implicit domain of memory, that i s, outside conscious awareness.

They do not occur in the conscious domain (i.e., are not insights and

do not require the unconscious becoming conscious). In fact, advances in

the psychotherapeutic process belong to the unconscious procedural

domain and occur throughout moments of meaning (Sanders, 1998;

Stern, 1998). These moments of meaning are specific moments in the

interaction between the patient and the therapist that allow the acquisi-

tion of new sets of implicit memories (Lyons-Ruth et al., 1998). These

moments increase the patient's range of procedural strategies for being

and doing, and a growth in these categories of implicit knowledge leads

to new strategies that are reflected in the ways a subject relates to

him/herself and to others, including the way the person interacts with

the therapist within the transference relationship. The subject's range of

implicit procedures and memories are affect-charged procedures that

originate from early experiences and that can be modified by different

stimuli. They may become more complex with subsequent affective or

relational experiences, including the experience of the psychodynamic

therapy. On the other hand, some authors have pointed out that the pri-

mary mechanism of therapeutic change is increasing conscious aware-

ness and making conscious the unconscious through interpretation. In

fact, according to Ryle (2003) the understanding induced by the

therapeutic experience and the relational knowledge should become

explicit in order to have a therapeutic effect.

It is likely that the changes induced by psychotherapy involve both

implicit and explicit domains of memory and knowledge and that, ac-

cording to a neuroscientific perspective, the psychological change oc-

curs because communication between brain circuits for implicit and ex-

plicit processes are stimulated leading to modifications and integration

of cognition, emotion, sensation, and behavior.

From a biological perspective it is important to point out that the im-

plicit domain of memory refers to the amygdala and its complex con-

nections to several brain areas (hypothalamus, limbic neocortical asso-

ciation areas, pre-frontal

cortex).

These brain areas appear to be critical

in the conscious evaluation of

emotions.

On the other hand, the explicit

domain of memory refers to the temporal lobe and its connections with

different brain areas that allow the conscious awareness of

experiences.

GENETIC

ND

MOLECUL R BIOLOGY STUDIES

According to Kandel s hypo thesis (Kandel, 1998 psychotherapy is ef-

fective

and

produces long-term changes

in

behavior presumably



682 MUNDO

through leaming. When leaming processes occur they induce changes

in gene expression that alter the streng th and the quality of synaptic con-

nections. The nature of the interaction betw een genes and environmen -

tal factors ( including rela t ionships and including therapeutic

experiences) is of param oun t im portance for the stud y of psychiatric

dis-

orders. Several familial an d m olecular biology stud ies have show n that

psychiatric disorders hav e a genetic compon ent and that this comp onent

may be significantly high for som e of them, such as schizophrenia, bipo-

lar disorder, and obsessive-compulsive disorder (Gottesman, 1991;

M undo et al., 2000,2003). Ho wev er, even for these conditions the influ-

ence of nongenetic, environmental factors appears to be significant. A

clear example of this environm ental influence can be found in the obser-

vation that in monozyg otic twins, wh o share

100%

of

genes,

the concor-

dance for schizophrenia or bipolar disorder rarely exceeds 50%

(Gottesman,

1991;

Kendler,

2001;

Wong, Gottesman,

Petronis, 2005).

This line of evidence has ind uced geneticists to consider psych iatric con-

ditions as complex disorders. A complex disorder in a genetic per-

spective is a disorder: that is quite frequent in the general population;

does not follow the Mendelian laws for heritability; and whose

pathogenesis implies the complex interaction of more than one gene al-

tered with more than one environmental pathogenetic factor, including

stressful early life even ts (Issa, 2002; Kendler et al., 1995). Even tho ug h

not all the genetic studies on gene-en vironm ent interaction in d etermin-

ing psychiatric illness gave concordant results (Kendler, Prescott,

Myers, Neale, 2003) some of them hav e clearly shown the role of life

events in determining risk of developing some psychiatric disorders to-

gether w ith the role of some gene va riants in conferring susceptibility to

psychopathology when stressful life events occur (Caspi et al., 2003;

Kendler et al., 2005). Among these life events loss, grief early

attachment experiences appear to have the most significant impact on

the development of psychopathoiogy.

In the light of these observations the challenge that genetics of com-

plex psychiatric disorders is facing at the daw n of the new m illennium is

no longer just finding the gene or the genes that may cause major psych i-

atric disorders b ut rather the study of the complex interactions between

genes and environm ent, and the way in which the environm ent in gen-

eral and life events specifically may modify the genetic risk of

developing a given con dition.

How ever, the natu re of the interaction between gene and environm ent

in determining each individual's attitudes, behaviors, or psychopath-

ology, appears to be far more complex. As an example, it has become

clearer that even in disorde rs that are not due to gene mutations or varia-

tions, genes play a substantial role. Gene expression modifications (i.e..




protein and neurotramsitter production modifications) occur as a conse-

quence of a wide variety of envirorunental factors, including drugs,

stressors, traumatic experiences, attachment experiences and experiences

occurring in the leaming and memory domains (Kandel, 1998). Several

animal studies have pointed out that environmental factors that occur

also very early in life may modify synaptic connections and brain plastic-

ity through the regulation of gene expression, and the same mechanisms

may occur in humans (Gabbard, 2000; Kandel, 1998; Suomi, 1991; Yeh,

Fricke, & Edwards, 1996). Interesting insights on this issue come from

molecular biology studies on leaming and memory processes.

Molecular mechanisms involved in leaming and memory, such as

long-term potentiation (LTP) and long-term depression (LT^D), occur

not only in the initial phases of the development of connections within

the central nervous system, but also throughout the individual's life, as

an effect of different experiences and life events. High order processes,

of which emotional memory is an example, imply that neuroplasticity is

occurring at increasingly larger numbers of synapses with increasing

complexity, organization, and reorganization. TTiis remodeling mech-

anism may lead to significant changes in behaviors and personality

traits (Post

&

Weiss, 1997). The molecular processes underlying memory

consolidation, and that lead to modifications in synaptic plasticity have

been hjq^othesized to be the molecular mechanisms of the change pro-

cess induced by psychotherapy. Psychotherapy has been suggested to

induce changes in the permanent storage of information and experi-

ences acquired by the subjects during their lifetime (Liggan & Kay,

1999). Among the wide variety of environmental factors that may

influence synaptic plasticity throughout learning and memory

processes,

w e

can include dynamic psychotherapy.

THE CH NGE PROCESS ND THE MODEL OF TR UM

Traumatic experiences have been considered a good example of the

changes occurring in the procedural domain (Horowitz, 1999) and also a

useful clinical example to build a significant interdisciplinary dialogue

with neuroscience and psychoanalysis (Tutte, 2004). Traumas may repre-

sent a model for the integration between neurobiology and interpersonal

experiences, particularly given the different nature and clinical characteris-

tics between traumatic and nontraumatic memories (Horowitz, 1999). Even

though all the experiences (traumatic and nontraumatic) may be implicitly

leamed and are processed through sub-cortical regions (i.e., basal ganglia)

function and connections, nontraumatic experiences more frequently be-

long to the declarative domain, and appear to be related to the function of

the hippocamus. The hippocam^pus sends stimuli to the association and



684 MUNDO

prefrontal cortex, inducing the consciousness and the symbolic representa-

tion of the memorized experiences (De Masi, 2004; LeDoux, 2002). On the

other hand, traumatic memories appear to belong mostly to the implicit

(nondeclarative) domain De Masi, 2004; Horow itz, 1999) regulated by the

amygdala. An excessive stimulation of this brain region would interfere

wilh the correct functioning of the hippocam pus, thus affecting the possi-

bility of proper symbolic representation and conscious awareness of the ex-

periences (De Masi, 2004; LeDoux, 1996). The retum of the memory of

traumatic experiences is accompanied by intense emotional and autonom ic

reactions an d usually by images or flashbacks rather than precise recollec-

tions of the traumatic events; in other words traumatic mem ories are usu-

ally not recovered as declarative m emories (Allen, 1995; Pally, 1998; Tutte,

2004) and the patient has usually no explicit awareness of his/her emo-

tional and autonomic reactions. As stated before, the brain region p rimarily

involved in this process is the amygdala with its complex connections w ith

the prefrontal cortex (Pally, 1998; Tutte, 2004). Several studies have also

shown that under stressful conditions the amygdala is hyperactive while

the hippocampus may show reduced activity and even become atrophic

(Bremner et al., 1997; Olds & Copper, 1997). Clinically these changes are

seen as impairments in attention and declarative memory.

The same procedural mechanisms involved in traumatic memories

appear to be involved in the change process induced by dynam ic psy-

chotherapy (Cimino & Correale, 2005). When patients are asked to re-

member the significant moments inducing change during their treat-

ment they usually remember affect-charged moments of interaction

with the therapist rather than psychodynam ic formulations or interpre-

tations prov ided by the therapist. The patient has usu ally no or few rec-

ollections of these decla rative processes (Gabbard, 2000). Howev er, it

has been pointed o ut that interpretations and consequent increased con-

scious awareness may produce also unconscious changes (Bleichmar,

2004). In addition, change occurring throu gh interpretation and change

occurring through the analytic relationship m ay share certain m olecular

mechanisms. As a consequence, the two therapeutic instrum ents (inter-

pretation and relationship) are successfully used together rather than

preferentially (Bleichmar, 2004).

In the Ught of these data and considerations it appears that the effects on

the brain of psychotherapy should be found in the areas involved in the im-

plicit mem ory processes, that is, the neocortex, the amygdala, and the cere-

bellum (Kandel, 1999). These are the areas that should be primarily investi-

gated using the current neuroimaging procedures, even though the

complexity of the change process induced by dynamic psychotherapy sug-

gests that many brain areas and many complex connections may be in-

volved.



NEUROBIOLOGY OF DYNA MIC PSYCHOTHERAPY 685

NEUROIM GING STUDIES

Unfortunately, there are no t many stu dies add ressin g the specific ef-

fect of dynam ic psycho therapy on brain areas and brain metabolism. In

addition, to date there are no studies show ing that brain changes associ-

ated with traumatic experiences can be reversed by dynamic psycho-

therapy. This prevents us from verifying the model of trauma resolution

as a model for the change induced by the psychotherapeutic process.

Ho wever, some interesting insights into the effect of memory and leam-

ing processes on brain structure m ay be found in neuroim aging studies

of the effect of traumatic experiences (Bremner et al., 1997; Putnam

Trickett, 1997) and traumatic experience recall (Shin et al., 2004).

Some confirmation of the presence of hippocam pus malfunction in sub-

jects who experienced traumas and of the fact that traumatic experiences

may induce changes in brain structure comes from Magnetic Resonance

Imaging (MRI) studies. Bremner and colleagues (1997) found that the

hippocampal volume of victims of childhood sexual abuse who subse-

quently developed Posttraumatic Stress Disorder PTSD) was significantly

smaller than that of norm al controls. On the other hand, other studies have

found no differences in the hippocampal volume between victims of trau-

mas and normal controls (Bonne et al., 2001; Fennema-Notestine et al.,

2002). In addition, the reduction of hippocampal volum e does not appear to

be specific, given that a similar reduction has been shown also in schizo-

phrenia and major depression patients (Hickie et al., 2005; Nelson, Sykin,

Hashm an, Riordan, 1998; Videbeck Ravnkilde, 2004). How ever, in

schizophrenia amygdala volume appears to be reduced as well (Nelson et

al., 1998) and in major depression the reduction of the hippocampus ap-

pears to be related to repeated episodes of the disease (Videbeck

Ravnkilde, 2004). Thus, while amygdala hyperactivity or increased vol-

um e m ay be specific to PTSD subjects (Shin et a l , 2004), it appears that the

hippocampus volume reduction is a consequence of untreated

psychopathology across different diseases and not specific to PTSD.

Studies investigating the effect of dynamic psychotherapy on brain

areas and brain m etabolism are few. The reason for this paucity of data

desp ite the recent increasing interest in the neurobiology of psych other-

apy an d the advanced status of neuroima ging techniques (Beutel, Stern,

Silbersweigh, 2003) is pro bab ly that the clinical effects of dynam ic

psycho therapy are usually seen over mo nths or years and neu roimag ing

follow-up studie s are difficult to carry on.

One of the first studies designed to investigate the neurobiological ef-

fect of dynam ic psychotherapy on brain fimction showed that dynam ic

psycho therapy alone, with no concomitant pharm acotherap y, may nor-

malize serotonin uptak e in the med ial prefrontal area and thalam us in



686 MUNDO

subjects with Borderline Personality Disorder and depressive symp-

toms Viinamaki et a l , 1998).

More recent studies have com pared the short-tim e effect on brain and

bra in me tabo l i sm of in te rpe rsona l psyc ho th e rapy IPT) and

pharmacotherapy in Major Depression patients. The first one is a Posi-

tron Emission Tom ograph y PET) stu dy do ne on subjects with Major

Depression and treated with either

IPT

or paroxetine. The

PET

scanning

performed before treatmen t showed

a

higher metabolism in

the

caudate,

in the pre-frontal cortex, and in the thalamus. After treatment both

groups showed a significant improvement in clinical symptoms.

Paroxetine-treated subjects show ed a metabolic reduction in right and

left pre-frontal cortex, while IPT-treated subjects show a reduction in

right pre-frontal cortex only. In addition, both g roups showed a reduc-

tion in anterior cingulate Brody et al., 2001). Ano ther paper using

SPECT method compared the effect of venlafaxine and IPT on brain

blood flow of depressed patien ts treated for six weeks Martin et al.,

2001). Both treatm ents in duced an increase in blood flow in basal gan-

glia w hile

IPT

only induced an increase in right

Umbic

areas . All subjects

showed a significant clinical improvement.

Another study has compared the effect on brain metabolism of

paroxetine treatment or cognitive behavioral therapy CBT) in Major De-

pression patients in order to verify whether

the

brain changes induced by

the antidep ressant response were specific for the different kind of antide-

pressan t treatment used Goldapple et

al.,

2004). Frontal and parie tal de-

creases together with hippocampal increases were seen in CBT-treated

patients, while paroxetine-treated patients show ed a reverse patt em . Of

particular interest

is

that

the

frontal metabolism decrease seen as an effect

of successfull

C T

in depressive subjects is similar

to

that seen

as

an effect

of successful

IPT

Brody et al., 2001). The question as to whether dynainic

psychotherapy, short-term IPT, and CBT affect different or similar brain

areas or whether similar brain changes may be induced by different

modes of psycho therapy is yet to be answered.

Unforhanately, there are no neuroimaging studies with longer fol-

lo w -u p pe riods that could be useful to clarify the long-term effect of dif-

ferent forms of psycho therapy on brain structure and metabolism.

ON LUS ONS

Recent advances in neuroscience appear

to

be able to provide soUd bio-

logical bases for the unde rstanding of djmamic psychotherapy theories and

practice.

Genetic, molecular biology, and neuroimaging studies have sug-

gested that environm ental factors, including early emotional and attach-




ment experiences, traumas, and the complex interaction between pa-

tient and therapist occurring during the process of dynamic

psychotherapy, may influence gene expression, synaptic plasticity, and

brain metabolism in specific areas.

Particularly, it has been hypothesized that the change process occur-

ring during dynamic psychotherapy resembles implicit memory and

leaming processes with the complex molecular changes these processes

imply. The new attachment relationship between the patients and the

therapist would create new sets of im^plicit procedures so that previ-

ously stored prototypes of attachment experiences, which are clinically

evident within the transference relationship, would be modified by the

new interaction with the therapist (Amini et al., 1996).

Few neuroimaging studies have also investigated the short-term effects

of dynamic psychoti:ierapy on brain metabolism and brain blood flow

(Brody et al.,

2001;

Martin et al., 2001). In these studies the changes induced

by IPT have been found to be different from those induced by

pharmacotherapy in depressed patients showing clinical improvement of

symptoms. However, it is stOl unclear whether the brain metabolism

changes induced by different forms of psychotherapy (e.g., dynamic or

CBT) are different.

Despite the significance of some of these findings and the important

potential implications for the understanding of the neurobiological ba-

sis of dynamic psychotherapy and for the clinical practice, most of the

clinical studies are preliminary and need further replication.

Thus, to think of a possible dialogue between neuroscience and dy-

namic psychotherapy some issues need further consideration.

The change process occurring during dynamic psychotherapy, in-

cluding the transference relationship and the moments of meaning

that pace the change process itself, are complex phenomena, too com-

plex to be reduced to implicit memory and learning mechanisms

(Gabbard, 2000).

Some authors have also criticized a neuroscience-based approach to

dynamic psychotherapy stating that the scientific method is inadequate

to explain the complexity of the therapeutic relationship and of the talk-

ing cure. The objective scientific method used in neurobiology studies

would not consider the subjective dimension of the therapeutic experi-

ence and thus, it would not be the adequate instrument to investigate the

mechanism of action of djmamic psychotherapy. In this view, a dia-

logue between neuroscience and dynamic psychotherapy appears to be

quite difficult using neuroscience instruments only.

However, there is another way to look at the concept of dialogue be-

tween neuroscience and psychoanalysis or dynamic psychotherapy.

All the attempts up to now to understand the neurobiological basis of



688 MUNDO

dynamic psychotherapy have started from the perspective of neurosci-

ence. Basically, they have u sed only neuroscience m ethods and language

and they have represented attempts to give dynamic psychotherapy or

psychoanalysis a solid scientific appraisal (Leeman Leeman, 2004).

The s tudies encountered whi le searching the l i te ra ture on

neurobiological aspects of dynamic psychotherapy teU us that this ap-

proach has proved useful, giving us clues about the nature of the interac-

tion between genes and environment, between synapses an d experiences,

maybe between brain and mind Also, these studies have provided us with

the instruments to hjrpothesize how d3mamic psychotherapy may produ ce

profoimd changes in behavior, relationships, and psychopathology by in-

ducing changes in gene expression, synaptic connections, or brain metabo-

lism. However, to date the attempts made to investigate these issues have

actually failed to explain the complexity of both psychopathology and the

complexity of the change process induced by dynamic psychotherapy. Ad-

ditionally, the application of psychoanalytic principles to explain contro-

versial results in neuroscience studies remains unexplored.

An attem pt in this direction of integrating different me thods and differ-

ent languages has been done

a

couple of years

ago.

At that time Buddhist

monks and neuroscientists m et at Cam bridge University

(MA) to

exchange

notes and insights on how the mind works. The outcome of this workshop

integrating different views on the natu re of mind has been reported in the

j o u r n a l cience in 2003 (Barinaga, 2003). During the work-

shop neuriscientists and Buddhist monks aimed to leam whe ther the

study of trained meditators can provide insights into the mechanisms of

brain function or on new therapeutic approches for clinical psychology.

One of the main

topics was to

define

the role

of introspection

(i.e.,

reporting

persona l mental experience) in science. On this topic neuroscientists and

Buddhists showed different points of view. For neuroscientists introspec-

tion cannot be a form of da ta, given the subjective dimension im plied by it.

On the other hand , for Buddhists introspection represents the basis for in-

vestigating the mind. Despite this difference in viewing subjective experi-

ence a common effort was made and a series of neuroimaging and

neuropsychological studies were planned to investigate how the subjective

experience and meditation training may modify brain activity. This reci-

procity in exchanging acquired know ledge should be the key of a truly inte-

grated approach to psychiatric disorders and psychopathology. Dialogue

should probably be viewed as an approach and a process implying a m u-

tual influence of neuroscience and psychoanalytic principles and language,

of objective methods and subjective experience, of biological and

psychological mechanisms.




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Dept. Of Psychiatry, Dept. Of Clin ical Sciences Lulg i Sacco

University of Milan

via G.B. CrassI 74, 20157 M ilan , Italy

e-mail: [email protected]

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