Attenuated Psychotic Symptoms Syndrome

Presented by Dr Pavan Kumar Chaired by Dr Joylin

Introduction
Schizophrenia affects 1 out of 100 people Onset during adolescence and early adulthood Personal and Societal costs are high Prevention of Schizophrenia substantial benefits Its Prodromal phase recognised since 19th century Psychosis is brewing long before its manifestation as a diagnostic illness and that there are identifiable signs and symptoms that precede the development of frank psychotic symptoms. (McGlashan et al, 2003). Over the last decade there has been a worldwide movement to develop comprehensive early intervention programs for schizophrenia.

Introduction - contd
Schizophrenia can be divided into three phases The 1st the premorbid phaseis a period of normality for most persons who ultimately develop schizophrenia. When deficits exist, they usually begin at birth and usually are subtle, stable, and asymptomatic. In the 2nd or prodromalphase--, symptoms occur with increasing severity beginning after puberty. This phase lasts between 2 and 5 years on average. Global functioning declines in an obvious downward, usually accelerating trajectory. The 3rd the psychotic phaseis ushered in with frankly psychotic symptoms. At this point, patients feel convinced that their hallucinations and delusions are real. Their earlier insight in the prodromal phase, consisting of recognition of attenuated psychotic experiences as false, is now lost.

Prevention of schizophrenia
Primary prevention tries to reduce the incidence of new cases in the population. Refers to intervention in the premorbid phase. Ex: improving prenatal care, reducing environmental insults and reducing mean paternal age . Secondary prevention aims to reduce the prevalence of the disorder. Prevalence could be reduced by efforts to delay onset of early signs and symptoms of the disorder Tertiary prevention aims to reduce morbidity, course progression, and mortality. Begins by treating schizophrenia as soon as possible after onset to reduce the duration of untreated psychosis and minimize the damage that active psychosis can wreak on the patients job, social life, and family functioning.

History
The prodromal phase of schizophrenia has been recognized since the early twentieth century by Bleuler. Emil Kraepelin described the onset of mostly negative and nonspecific symptoms followed by positive symptoms and then the first psychotic episode. According to the Kraepelinian view, the sequence of deterioration is immutable There is proposal to include this risk syndrome in DSM V prior its publication.

What is Prodrome?
Describes retrospective concept because until there is an established psychotic illness such as schizophrenia it cant be defined. (Yung et al, 1996). Refers to the time period characterized by mental state features which represent a change from a persons premorbid functioning up until the onset of frank psychotic features (Yung et al. 1996).

 Approximately 80-90% of pts with schizophrenia report a variety of symptoms, including changes in perception, beliefs, cognition, mood affect, and behavior that precede psychosis, although approx 10-20% develop psychotic symptoms precipitously without any apparent significant prodromal period (Yung & McGorry, 1996a). The typical pattern is that the non-specific symptoms and negative symptoms develop first, followed by attenuated, or mild, positive symptoms, together with distress and decreased functioning (Hafner et al, 1998).

Prodromal criteria
It has been recognized for years that some individuals who develop schizophrenia have subtle social, behavioral, and intellectual deficits such as impaired motor development and coordination, neurological soft signs, lower intelligence, and a broad range of social problems. Yung et al (1996) in Melbourne developed a specialized clinical setting, the Personal Assistance and Crisis Evaluation Clinic (PACE) to study and treat individuals who present for help and concerned about symptoms that appear to be psychotic in nature. These individuals were considered to be at ultra-high risk , the term adopted as alternative to prodromal.

vulnerability group 1. first degree relative with psychosis or patient with schizotypal personality disorder. 2. 30% drop in Global Assessment of Function (GAF) score from premorbid level, sustained for 1 month 3. Change in functioning occurred in the last year

Attenuated symptom group 1. specified severity rating on at least one or more attenuated positive symptoms 2. specified frequency rating over a given time period 3. symptoms present in past year and for not longer than 5 years Brief Limited Intermittent Psychotic Symptoms (BLIPS) group 1. specified severity rating of brief psychotic symptoms 2. specified frequency rating over a given time period 3. each episode of symptoms is present for <1 week and spont remit on every occasion. 4. symptoms present in past year and not longer than 5 years.

 Almost identical criteria, the Criteria for Prodromal Syndrome (COPS) have been developed by Mc Glashan at Yale University. Similarly basic symptom concept which originated in the observation of deficits that were perceived by individuals with schizophrenia of 10 yrs before the first manifestation of psychotic symptoms. (Bonn Scale for the Assessment of Basic Symptoms, BSABS)

 Using the criteria the risk of psychosis increases from approx 10% in genetic high-risk group to approx 30-50% Reliability of the diagnosis has shown to be excellent and studies using these criteria support that prodromal persons are symptomatic and at high and imminent risk for psychosis.

 DSM V prefers a name Attenuated Psychotic Symptoms Syndrome or APS Syndrome for prodrome Proposed revision in DSM-5 criteria for identifying attenuated psychotic symptoms syndrome a) Characteristic symptoms:at least one of the following is present in attenuated form with intact reality testing but of sufficient severity and/or frequency that it is not discounted or ignored i. Delusions ii. Hallucinations iii. Disorganised speech

b) Frequency/currency: Symptom or symptoms meeting criteria A must be present in the past month and occur at an average frequency of at least once per week in the past month c) Progression : Symptoms meeting criteria A must have begun or worsened in the past year d) Distress/disability/treatment seeking: Symptoms meeting Criteria A are sufficiently distressing and disabling to the patient and/or parent/guardian/others to lead them to seek help e) Symptoms meeting criterion A are not better explained by any other DSM 5 diagnosis, including substance related disorders f) Clinical criteria for any DSM-V frank psychotic disorder have never been met

 Name was changed from psychosis risk syndrome to attenuated positive symptom syndrome This emphasises that symptoms already present rather than potential for predicting future psychosis As a result false positive diminished But new issues raised Attenuated psychosis syndrome is included in Section III of the new manual; conditions listed there require further research before their consideration as formal disorders. DSM 5 Criteria is less inclusive than research criteria

EPIDEMIOLOGY
Although meticulous epidemiological studies of the prodrome have not yet been done, it is believed that the incidence of prodromal patients will mirror that of patients with schizophrenia (approximately 1 per 10,000) but that prodromal patients will be on average 12 years younger.

Clinical rating scales for the Prodrome

3 specific scales have been developed Comprehensive Assessment of At Risk Mental State (CAARMS) Scale of prodromal Symptoms (SOPS) and Structured Interview of prodromal Symptoms (SIPS) Schizophrenia prediction Instrument for Adults (SPI-A)

Transition to Psychosis
Two large multisite studies North American Prodrome Longitudinal Study (NAPLS) Approx 35% converted to psychosis over 2.5 yr follow-up period and Five features at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment and history of substance abuse. European Prediction of psychosis Study (EPOS) 62% transition to schizophrenia, 16% mood disorder with psychotic features and the rest schizoaffective and schizophreniform disorder

 The PACE Clinic in Melbourne has shown a prospective risk of conversion or positive predictive value of 40.8% within the first 12 months in 49 prodromal patients (Yung et al. 2003). Most recently, a follow-up study of 104 ultra-high-risk patients reported that 34.6% of the patients developed frank psychotic symptoms within 12 months (Yung et al.2004) In the PRIME Clinic sample, most of the patients who did not progress to schizophrenia remained prodromal, and only a few experienced remission of prodromal symptoms within 12 months.

Predictors of Transition
Unusual thought content, suspicion/paranoia and bizarre thinking predicted transition Negative symptoms but not as strongly as positive symptoms Low functioning over last year Street drug use (cannabis and amphetamines)

 Cognitive deficits Intermediate between healthy controls and first episode psychosis Spatial working memory, verbal declarative learning and memory and attention Deficits in sustained attention stable vulnerability marker Deficits in verbal declarative memory predictive of conversion to psychosis. Social functioning GAF score of 50 or low Facial affect recogntion deficits- vulnerability marker

Neuro imaging
cerebral gray matter volume deficits have been found in several cortical regions on magnetic resonance imaging studies progressive reductions in gray matter in the left parahippocampal, fusiform, orbitofrontal, and cerebellar cortices and the cingulate gyri

Differential Diagnosis of the Prodrome

The prodrome signals the impending onset of disorders other than schizophrenia, making the differential diagnosis of the prodrome a critical and challenging exercise. rule out general medical conditions that can mimic a prodromal state and/or progress to frankly psychotic symptoms, such as Cushings disease, delirium, certain seizure disorders, lupus, and various types of drug intoxication Drug dependence, such as chronic marijuana use in particular, may lead to amotivation, dysphoria, perceptual abnormalities, and paranoia.

 Major depression with psychotic features: Depressive symptoms are common in the prodrome. Most prodromal patients, however, do not meet full diagnostic criteria for major depression and complain of emotional numbness rather than true sadness or sustained irritability. Schizotypal personality disorder. Distinguished mostly by course. Symptoms in the prodrome are progressive, not static. Borderline personality disorder: BPD traits are present usually from an early age and are unlikely to show sudden emergence in young adulthood. Pervasive developmental disorder: may resemble the prodrome in some ways, it is usually associated with mental retardationand other GMCs.

 Posttraumatic stress disorder. Unlike prodromal symptoms, PTSD develops after a psychologically traumatic event that is generally outside the range of usual human experience. Obsessive-compulsive disorder (OCD). Prodromal patients usually do not show compulsive behaviors or preoccupation with the classic OCD themes of contamination or inadvertent harm to others, and they do not experience OCD symptoms as ego-dystonic. Attention-deficit/hyperactivity disorder (ADHD). Although attention deficits are common in the prodrome, patients with true ADHD usually are identified before age 7 years.

TREATMENT
Two controlled studies involving treatment of prodromal symptoms with atypical antipsychotic medications have been done. The results of 1st study provide strong support for the ability of an atypical antipsychotic medication in conjunction with CBT to postpone, rather than eliminate, progression to psychosis among prodromal patients McGlashan et al. (2003) conducted a double-blind, placebo-controlled trial of olanzapine in 60 prodromal patients. The 1-year results showed that 16 patients became psychotic, including 11 (of 29) from the placebo group and 5 (of 31) from the olanzapine group.

TREATMENT RECOMMENDATIONS
Early identification and treatment of the prodrome at the PRIME Clinic have had several benefits, including reduced psychosocial morbidity. Patients and their families express relief that the condition is recognized, monitored, and treated with minimal disruption of daily life and usually on an outpatient basis. Social withdrawal and isolation are reduced, and families receive emotional support and education about the prodrome.

 active follow-up care at frequent intervals assessment of global functioning at baseline and at periodic intervals supportive therapy for the patient, family therapy, psychoeducation, and liaison with other treating physicians and therapists. Safety issues, including substance abuse, poor self-care, and suicidal and homicidal behavior, must be vigorously addressed. Comorbid disorders should be treated.

 Treatment of the prodrome with conventional antipsychotics currently being used in the treatment of schizophrenia is still in its research phase and is not recommended for standard treatment. From a research perspective, drugs that target mechanisms of action such as excessive oxidative stress and hypofunction of the Nmethyl- Daspartate subtype of glutamate receptors may be beneficial, including glycine, omega-3 fatty acid supplementation, and lamotrigine.

Issues
Benefits of inclusion in DSM V Clinical validity of the syndrome Stigma Unnecessary treatment Ethical dilemma

Benefits of inclusion of a new APS syndrome category in DSM 5

Widespread community education about who does and does not meet risk syndrome criteria Promotion of more rapid and larger scale treatment research

Risk of inclusion are

Stigma Overmedication of false positive patients

=both of these can be overcome by education =also DSM 5 diagnosis are not necessarily greater than those with DSM IV diagnosis these patients now receive, such as psychosis NOS

 If use of antipsychotic treatment becomes standard in absence of clinical trials and patients improve than assumption will be that it was due to medication and it will increase overmedication

 False-positive diagnoses are likely to occur with disorders such as major depression, bipolar disorder, OCD, and schizotypal personality disorder Although false-negative diagnoses are also likely to occur, PRIME Clinic sample found that patients who had not initially met prodromal criteria did not progress to psychosis within the next year. Also lack of information about conversion rates . It keeps changing quite substantially with 50% in early studies to 20% in current studies.

Conclusion
Identification of individuals at the prodromal stage of illness would offer clinicians the oppurtunity to provide preventive interventions But evidence for efficacy of pharmacological and psychosocial intervention needs to be strengthened New changes are difficult to be accepted at the very onset, with passage of time, experience and constructive discussion, opinions change. We hope the change would be for benefit of people suffering from schizophrenia and psychotic disorders

THANK U