AT RISK MENTAL STATE (ARMS), ULTRA HIGH RISK (UHR) AND ATTENUATED PSYCHOSIS SYNDROME

- Dr.SRIRAM.R

What is ARMS?

• Refer to these individuals who appear to be at risk of psychosis but in whom psychosis is not inevitable. (McGorry and Singh, 1995)

• Not all people with operationally defined subthreshold forms of psychosis will go on to develop a diagnosable psychotic disorder such as schizophrenia.

• The ‘‘natural history’’ of the ARMS criteria was examined. A transition rate of 41% was demonstrated. (Yung et al., 2003)

• Factors that predict an increased likelihood of the development of psychosis are – Long duration of subthreshold (‘prodromal’) symptoms Poor functioning at presentation High levels of depressive symptoms Higher attenuated symptoms (c/f attenuated syndrome)

ARMS and “Prodrome”• Prodromal means all the people who have it, WILL develop

psychosis (100% certainty).• Prodrome of schizophrenia has initially been defined as

“an early or premonitory manifestation of impending disease, before specific symptoms begin”

• So prodrome is a retrospective concept rather than a prospective concept.

• If it is not clear 100% at the time of their presentation whether psychosis will follow or not, then “ARMS” should be used.

• So ARMS is a prospective concept introduced for early identification of psychotic patients.

• People with ARMS are whom intervention at an early stage, before onset of frank psychosis, could be justified in order to prevent further deterioration and suffering.

Why is ARMS/Prodrome important?• Can lead to severe functional impairment, stigmatizing

disabilities and life-threathening consequences.

• Persistence of those disabilities prior to the onset of full positive psychotic syndrome may lower the possibility of eventual recovery (Schultze-Lutter et al. 2008, Marshall et al. 2005, Perkins et al. 2005, Fusar-Poli et al. 2009)

• Preventive treatment could minimize alterations in brain structure, as well as neurobiological changes, which could lead to substantial improvement of the prognosis (Nelson et al. 2008)

Clinical Criteria for Detection of Patients at High Risk for psychosis

1. UHR criteria (Personal assessment and crisis evaluation clinic, Melbourne)

2. Basic symptoms criteria

ULTRA HIGH RISK(UHR) CRITERIA

ULTRA HIGH RISK (UHR)

Because of the non-specific nature of the ARMS as well as absence of the

“Prospective” definition of prodrome (Yung et al., 1996), the concept of “Ultra

high risk” for psychosis was introduced by researchers in Melbourne, Victoria in

2003, which has subsequently undergone many changes, and further studies, the

recent one being in early 2014.This concept of “Ultra High Risk” is a

refined extension of ARMS

2003-04

•Subjects were recruited into this study from the Personal Assessment and Crisis Evaluation (PACE) Clinic, Melbourne, Australia (Yung et al., 1995, 1996).

•All referrals to the Clinic between March 1995 and January 1999 were screened for inclusion.

•Referral sources included general practitioners, psychiatric services, school and university counseling services, and other support agencies working with young people, such as drug and alcohol services.

Subjects were included in the research program if they

(a)were aged between 14 and 30 years(b)Met criteria for one or more of the groups

outlined (c)had not experienced a previous psychotic

episode(d)were living in the Melbourne metropolitan

area

Exclusion criteria were: intellectual disability, lack of fluency in English, and presence of known organic brain disorder or previous psychosis

Essentially there are three sets of separate intake criteria FOR UHR people :

Group 1: Attenuated psychotic symptoms (APS)

Group 2: ‘‘Brief Limited Intermittent Psychotic Symptoms’’(‘‘BLIPS’’)

Group 3: Trait and State risk factors

Scales used in this study -

• Brief Psychiatric Rating Scale 24 item version (BPRS) (McGorry et al., 1988)

and•the Comprehensive Assessment of

Symptoms and History (CASH) (Andreasen, 1987) which were used to measure the intensity of a psychotic symptom

REVIEW OF SUBCOMPONENTS OF THE SCALES USED

BPRS SUBCOMPONENTS included in PACE criteria

•11 – UNUSUAL THOUGHT CONTENT

•10 – HALLUCINATIONS

•9 – SUSPICIOUSNESS

•15 – CONCEPTUAL DISORGANISATION

CASH rating scale – delusional subcomponent included in PACE

Group 1 - Attenuated Psychotic Symptoms

• Symptoms that deviate from normal phenomena but which are not yet frankly psychotic eg. Overvalued idea.

• The duration of attenuated psychotic symptoms should be <5 years.

• This limit on the duration of the attenuated psychotic features was included as long duration trait phenomena (schizotypal personality disorder) rather than acute mental state change.

• However, subjects meeting this criterion might well have other

symptoms, such as depressed mood or anxiety, lasting over 5 years.

• Thus the maximum duration of symptoms applies only to the

actual psychotic-like phenomena.

Group 2: ‘‘Brief Limited Intermittent PsychoticSymptoms (BLIPS)’’

• Symptoms of psychotic intensity but which have a total duration of <7 days before resolving spontaneously.

• A recency criterion is included for this group: symptoms must have occurred within the last year.

• Someone with a brief psychotic experience which occurred over 1 year ago would be excluded from the study as the period of risk is thought to be no longer current.

Group 3 ‘‘Trait and State Risk Factors’’

• Have nonspecific symptoms such as

lowered mood or anxietyplus

some trait risk factor for psychotic disorder (schizotypal PD) or a family history of a psychotic disorder in a first-degree relative

at least 1 month to not longer than 5 years (to exclude trait phenomena)

• Have marked disability or decrease in functioning.

• This severity criterion is necessary to exclude otherwise normal relatives of patients with psychotic illnesses who have a brief period of

mild symptoms.

• A recency criterion of deterioration within the last year is also included so that people who deteriorate but who then recover are not labeled as

high risk as the period of risk is thought to be no longer current.

When does subject become psychotic?• If it is a delusion, it is acquisition of delusional conviction

and preoccupation with the belief.

• Essentially the definition of psychosis describes a clinical picture of frank delusions, hallucinations, or formal thought disorder present most of the time and for at least one week (Exclusion criteria in this study)

• NOTE – This definition used here is for antipsychotic rx rather than a diagnostic category as endpoint, and does not conform to DSM-IV standards

RESULTS?

• Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months.

•Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months.

•Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis

2006

RESULTS of 2006 study

• UHR+ individuals were significantly more likely to become psychotic than UHR- individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5).

•Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group.

A.R. Yung et al. / Schizophrenia Research 84 (2006) 57–66

RECENT STUDIES in UHR criteria• More recent studies (Yung et al. 2007, McGorry et al. 2008,

Cannon et al. 2007) tends to show a lower rate of annual transition (20-35%), which could be due to earlier detection, improved efficacy of intervention and a “dilution effect” (greater portion of population included)

• 30-35 % risk of psychosis within 1 to 2 years of follow-up among UHR cases, a rate definitively higher that the incidence rate of psychosis in the general young population (Cannon et al. 2007)

• A large longitudinal North American study published in 2009 shows that 40% of the 377 patients assessed by the Structured Interview for Prodromal Syndromes (SIPS) as meeting criteria for prodromal syndromes, converted to fully psychotic illness during the 2.5 years of follow-up (Woods et al. 2009)

BASIC SYMPTOMS CRITERIA (Koch et al. 2010, Nelson et al. 2008)

• The annual conversion rate for sample meeting basic symptoms criteria is around 25% (Koch et al. 2010)

• Rate of conversion reaches 70% in a study with a 110 patient’s follow-up of 9.6 years, with a mean time to onset of 5.6 years (Nelson et al. 2008)

• Some authors consider that the Basic (Cognitive) Symptoms precede the onset of APS and BLIPS according to according to Comprehensive Assessment of At Risk Mental States (CAARMS) criteria (Koutsouleris et al. 2009)

• A 2010 German retrospective study exploring the time-related syndromic sequence preceding the onset of full-blown psychosis (Shultze-Lutter et al. 2010) DID NOT CONFIRM ABOVE FINDING.

2014

• In a naturalistic 48-month follow-up study, the conversion rate to first-episode psychosis was studied in 246 outpatients of an early detection of psychosis service (FETZ); thereby, the association between conversion, and the combined and singular use of UHR criteria and COGDIS was compared.

• Patients that met UHR criteria and COGDIS (n = 127) at baseline had a significantly higher risk of conversion (hr = 0.66 at month 48) and a shorter time to conversion than patients that met only UHR criteria (n = 37; hr = 0.28) or only COGDIS (n = 30; hr = 0.23)

FINAL VERDICT???

UHR positivity PLUS COGDIS positivity = GREATER RISK FOR CONVERSION to

PSYCHOSIS within 6 years.

ATTENUATED PSYCHOSIS SYNDROME

Copyright © American Psychiatric Association. All rights reserved.

From: Should Attenuated Psychosis Syndrome Be a DSM-5 Diagnosis? (Carpenter and Van Os)

Am J Psychiatry. 2011;168(5):460-463. doi:10.1176/appi.ajp.2011.10121816

Proposed Criteria for Attenuated Psychosis Syndrome

Figure Legend:

Where is it actually in DSM-5?• At first glance, it seems to be included in “Conditions for

further study” in Page 783.

• Is it there in the main text? YES. It is given as an example 3 in Other Specified Schizophrenia Spectrum and Other Psychotic disorder 298.8 (F28 in ICD-10 as Other nonorganic psychotic disorder) in Page 122.

• As an “Other” disorder with its own numerical code, APS can now be diagnosed and used to bill for insurance reimbursement, although the DSM-5 Psychosis task group initially promised it would not include it.

• So technically, ATTENUATED PSYCHOSIS SYNDROME is very much an already existing diagnosis.

Why should it not have been included in DSM-5?

• Many attenuated symptoms are quite stable and do not lead to more severe illness, as in individuals who have schizotypal personality disorder, who rarely become psychotic, or in the nearly 10% of normal individuals who believe in sorcery or aliens or hear voices.

• No proven treatment for this syndrome. Attempts to institute early antipsychotic treatment have shown no long-lasting effect and only exposed these individuals to drug side effects.

• Research also requires a consensus among researchers and funding agencies that a population of affected persons can be identified.

Contd.• Premature diagnosis may have negative consequences on

the expectations and acceptance of others in the individual’s social environment (People diagnosed are young).

• Field testing will assess whether the diagnosis can be made reliably over time by different clinicians on the same patient and in agreement with those who have conducted the initial research.

• ULTIMATELY, WHY IT should not have been INCLUDED IS BECAUSE OF INSUFFICIENT FIELD TESTING AS WELL AS INCONCLUSIVE TREATMENT PLANS AND/OR INAPPROPRIATE TREATMENT.

TREATMENTS?• Diminution of the transition rate about 15% in favor of the

antipsychotics which reached statistical significance only in the studies using risperidone and amisulpride (McGorry et al. 2002, Rurhmann et al. 2007).

• A randomized, placebo-controlled trial (Amminger et al. 2010) involving long chain omega-3 FA with a 12-week intervention and 40-weeks monitoring period showed a reduction of 22.6% (28% to 5%) of the cumulative risk of progression to full-threshold psychosis for the intervention group.

• Long-chain Ω-3 fatty acids also significantly reduced positive, negative and general symptoms and improved functioning, compared with placebo.

• A randomized study (Morrison et al. 2004) comparing CBT over 6 months with monthly monitoring in 58 patients meeting UHR criteria showed a 15% reduction of the rate of conversion to full blown psychosis.

• Seventy-nine patients were randomized to Integrated model treatment (Modified Assertive Community Treatment, Social skills training, and Psycho-education in multiple-family groups). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment vs standard treatment (48.3%) (Nordentoft et al. 2006).

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