Prodrome – directions in reaserch on the Psychosis prodrome

SUMMARY

The prodrome, or a period of clinical and functional decline, represents the period between the premorbid phase and the beginning of frank psychosis and offers an unique opportunity to implement early intervention strategies. It can be diffi cult to indentify this prodromal period, but the Structured Interviw for Prodromal Syndromes (SIPS) and Th e scale of Prodromal Symptoms ( COPS) can be useful. Th e results of this instruments can be framed, using criteria, in three distinct syndroms: Attenuated Positive Symptom Syndrome, Brief Intermittent Psychotic Syndrome, Genetic Risk and Deterioration Syndrome. Th is period can last from a few months to years but, it is only a transitional diagnostic, being, eventually, framed into a DSM diagnostic.

Key words: Prodrome, psychosis, basic symptoms.

In this article we review the research literature on the prodrome to psychosis based on studies of individuals who meet clinical high risk criteria [1].

Retrospective and prospective studies have shown that the prodrome can last from months to years prior to the clinical onset of psychotic symptoms [2].

By definition, prodromal symptoms are subclinical manifestations of the perceptual, ideational and behavioral symptoms of psychosis.

In this research literature, these syndromes are refferded to as CHR (Clinical High Risk), UHR (Ultra high Risk), ARMS (At risk mental state) or Prodrome [1,3]. An “Attenuated Psychosis Syndrome” is included in section 3 of DSM V to encourage further study and diagnostic consideration. A UHR criteria have been defined to prospectively identify people in this prodromal phase.

The psychosis prodrome, or a period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanism of psychosis onset and testing early intervention strategies [1].

Prodrome in clinical medicine refers to the early symptoms and signs of illness preceding the characteristic manifestations. The widely accepted definition of prodrome was given by Keith and Mathews in 1991 as a “heterogenous group of behaviors temporally related to the onset of psychosis” [4].

This prodromal phase should also be compared to the DSM-IV concept of fully psychotic disorders that have not been present for long enough to meet the criteria for schizophrenia or schizoaffective disorder. These DSM-IV concepts are psychotic disorders not otherwise specified, brief psychotic disorders and schizophreniform disorders.

Two concepts of early detection of pacients at risk of psychosis are the focus of this current research: the UHR criteria and the basic symptom approach [5].

Most studies indicate that the URH criteria (attenuated positive symptoms-APS, brief intermittent limited psychotic symptoms-BLIPS), or a combination of genetic risk indicators and recent functional deterioration-GRDS) reported a transition rate to psychosis of 35% to 54% whithin 12 months [3]. Further analyses resulted in a second basic symptom criterion based on 9 cognitive disturbances (COGDIS) that was associated with a transition rate to psychosis of 23,9% at 12 months and 46,3% at 24 months [5].

The UHR approach consists of 3 alternative criteria:

– Attenuated positive symptom-APSS were defined by at least one of the following symptoms with a moderate to severe but not psychotic (35) SIPS score appearing several times per week for at least 3 months: unusual thought content, delusional ideas, souspiciosness, persecutory ideas, grandiosity, perceptual abnormalities, hallucinations, disorganized communication and odd behavior or appearance.

– Brief limited intermitend psychotic symptoms (BLIPS) were defined by hallucinations, delusions or formal thought disorders that occurred within the last 3 months resolved spontaneously within 1 week scored as severe and psychotic (score of 6) on the SIPS, and scored as at least moderate on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS)

– Genetic risk and functional deterioration (GRD) were defined by: a 30%, or greater, reduction in score on the modified version of the Global Assesment of Functioning Scale (GAF-M) for at least 1 month within the previous year compared with the highest level of previous functioning and having a first or second degree relative with a history of any DSM-IV psychotic disorder or having a DSMIV schizotypal personality disorder [5].

Assesing the prodrome, MC Gorry and Yung in Mellbourne, Australia, were the first reaserchers to define putative risk criteria for psychosis.

MC Glashan and Miller in the United States developed the Stuctured Interview of Prodrome Symptoms (SIPS). Researches in Germany have proposed an alternative approach for identifying individuals at clinical risk for psychosis based on the concept of basic symptoms with the Bonn Scale for the Assesment of Basic Symptoms (BSABS) [6,7,8].

Several cohort studies and clinical trials have reported on demographic, clinical and other predictors of conversion (EPOS – European Prediction of Psychosis Study; PACE – Personal Assesment and Crisis Evaluation); EDIE – Early Detection and Intervantion of Psychosis Study; NAPLS – North American Prodromal Longitudinal Study).

The most well replicated finding is the relationship of baseline-attenuated positive symptom severity with psychosis onset, whether this is measured by PANSS, CAARMS or SIPS [9].

NAPLS and EPOS reported that unusual thought content, suspicion/paranoia and bizarre thinking/ a disorganization syndrome feature predicted conversion.

PACE and NAPLS reported negative symptoms, low functioning as measured by changes in GAF scores predicted conversion.

In the Dutch Prediction of Psychosis Study, it has been established an individualized estimator using instruments yielding data of neuropsychology, simptomatology, environmental factors, premorbid adjustment and neurophysology.

The EPOS introduced a prognostic index based on a 6-variable prediction model including global functioning within the previous year.

In the NAPLS, a combination of 3 baseline variables (genetic risk with recent functional decline, higher levels of unusual thoughts or suspiciousness and more severe social impairment) resulted in a marked increase of the positive predictive power [10].

PACE study suggest that conversion to psychotic illness over six monthts is most likely when initial diagnosis is BLIPS followed by APSS and GRD.

Several different outcomes are possible in patients at risk for psychosis: conversion to psychosis, asymptomatic recovery and slable presentation of prodromal symptoms. Schlasser et al 2011, reported that although 30% of their UHR sample developed psychosis within two years (30% experienced remission, 30% evidenced limited functional recovery).

The nonconverters continue to display a range of psychiatric problems and functional difficulties over time. Many experience nonpsychotic DSM IV Axis I conditions such as mood and anxiety disorders that warrant intervention.

The pacients who meet the criteria for prodrome often present with comorbide diagnoses, in particular anxiety, depression, substance abuse disorders, negative symptoms, significant impairments in academic performance and difficulties with interpersonal relationships, social withdrawal and isolation, cognitive impairment (verbal IQ, verbal memory and fluency and attention, difficulties in identifying and verbalizing their own emotions, independent of intelligence scores, social inadequancy and schizotypal traits [9].

These problems have been present for some time but recently worsened. A GAF score of 50 or below at baseline was associated with psychosis at 12 months follow-up [11,12].

PRODROMAL ASSESSMENT WITH THE STRUCTURED INTERVIEW FOR PRODROMAL SYNDROMES(SIPS) AND THE SCALE OF PRODROMAL SYMPTOMS (COPS)

The SIPS is a structured diagnostic interview used to diagnose the three prodromal syndromes and may be thought of as analogous to the Structured Clinical Interview for DSM-IV (SCID).

This instrument was developed by the Prevention Through Risk Identification Management, an Evaluation (PRIME) prodromal research team in Yale University.

The SIPS includes the SOPS, the Schizotypal Personality Disorder Checklist (APA 1994), a family history questionnaire and a well anchored version of the Global Assesment of Functioning scale [13].

The SIPS also includes operational definitions of the three prodromal syndromes (the Criteria of Prodromal Syndromes [COPS]) and an operational definition of psychosis onset (Presence of Psychotic Syndrome [POPS]). As part of the SIPS, the COPS and the POPS are applied to the information from the positive symptoms of the SOPS, the Schizotypal Personality Disorder Checklist, and the family history questionnaire to diagnose a prodromal syndrome or the presence of psychosis. The SOPS is a 19-item scale designed to measure the severity of prodromal symptoms [13].

The Brief Intermittent Psychotic Symptom syndrome (BIPS) is defined by the experience of frankly psychotic symptoms that do not meet POPS criteria, have reached a psychotic level of intensity only within the past 3 months, and occur at least several minutes per day at a frequency of at least once per month. Thus, clinically, people meeting the BIPS criteria would appear to be experiencing frankly psychotic symptoms of recent onset that are present infrequently and for short periods of time. The Genetic Risk and Deterioration syndrome (GRD) is defined by having a genetic risk, in the form of a first degree relative with any psychotic disorder, or personally meeting the DSM-IV criteria for schizotypal personality disorder, as well as having a significant drop in functioning as defined by a GAF drop of 30 percent or more over the past year. This syndrome was included in part to capture individuals who may be experiencing a prodromal phase that is predominantly characterized by negative symptoms, which we expect will be reflected in the significant drop in functioning as measured by the GAF. The final syndrome, and in the PRIME samples by far the most frequent of the three, is the Attenuated Positive Symptom syndrome (APS). This syndrome is characterized by the development or worsening within the past year of mild or attenuated psychotic symptoms that have not yet reached a psychotic level of intensity and have been present at least once per week in the past month. The characteristics of mild or attenuated positive symptoms are familiar to most clinicians but have generally not been the focus of sustained investigative attention until recent years. These patients report experiencing the precursors to delusions, hallucinations, and thought disorder in the form of unusual thought content, perceptual abnormalities, and disorganized speech. Unusual thought content in the attenuated realm can be of a paranoid, grandiose, or other nature and may range from mild to severe but not to psychotic. Clinical examples of this type of symptom include patient reports of considering the possibility, but clearly not believing, that others might be able to read their minds, that they might be able to read others’ minds, or that they might be able to predict or determine the future from dreams. One of the key determinants of a symptom being considered attenuated and not at a fully psychotic level of intensity is the lack of conviction regarding the externally generated, “real” nature of the symptom as well as the maintenance of insight regarding the sense that the experience is, in fact, a symptom [13].

Perceptual abnormalities in the attenuated realm can equally be experienced at a mild to a severe but not at a psychotic level of intensity. Patients experiencing such symptoms can report hearing odd noises, such as banging or clicking or ringing; dogs barking when there is no animal present; or their name being called when no one has called them. More severe but still attenuated symptoms have been described as hearing sounds or voices that seem far away or mumbled. People also report experiencing vague perceptual changes such as seeing colors differently, seeing flashes of light, or seeing geometric shapes [13].

Finally, because thought disorder is a subjective experience that is difficult for the observer to assess, the SIPS measures this experience through disorganized speech. Clinically, we look for people who over time have become circumstantial or tangential in their speech, who are using odd words or unusual phrases, or who otherwise are beginning to have difficulty getting the point across [13]. The prodrome has some similarity on a conceptual basis to “spectrum” and other schizophrenia-related constructs but is sharply distinguished from them.

The prodrome construct is like schizotypy and schizotaxia in that symptoms are milder than in frank schizophrenia but differs from them in that symptoms are of relatively recent origin and escalating in severity rather than being stable and enduring.

The prodrome construct is similar to the concept of “children at risk” in sharing heightened risk for future progression to schizophrenia but differs in requiring that the state be symptomatic, in not requiring that family history of schizophrenia be present, and in connoting greater imminence of risk. The prodrome construct should also be compared and contrasted with DSM-IV conceptualizations of fully psychotic disorders that have not been present long enough to meet criteria for schizophrenia or schizoaffective disorder. These DSM-IV concepts are psychotic disorder not otherwise specified (NOS), brief psychotic disorder, and schizophreniform disorder. These DSM-IV concepts do not overlap with the APS or GRD prodromal syndromes. However, some patients who are late in the course of the BIPS prodromal syndrome as defined by the SIPS could simultaneously meet criteria for early DSM-IV schizophreniform disorder. For this overlap to occur, the brief intermittent psychotic symptoms would have to have been present between 1 and 3 months and also meet DSM-FV schizophreniform disorder criteria of being present “a significant portion of the time [13].

The criteria for onset of frank psychosis used are the POPS criteria, part of the SIPS interview.

The POPS requires that one or more of the positive items from the SOPS be scored at a psychotic level of intensity and also describes psychotic symptom frequency and duration criteria [13].

CRITERIA OF PRODROMAL SYNDROMES [10]

1. Attenuated Positive Symptom Syndrome

1.1. Severity rating of moderate (3), moderately severe (4), or severe but not psychotic (5) on any one of the 5 SIPS positive symptoms

1.2. Symptom occurs at above severity level at an average frequency of at least once per week in the past month

1.3. Symptom must have begun in the past year or currently rates at least one scale point higher than rated 12 months previously

2. Genetic Risk and Deterioration Syndrome

2.1. First-degree relative with psychosis or patient with schizotypal personality disorder

2.2. 30% drop in Global Assessment of Functioning score compared with that 1 year ago, sustained over the past month

3. Brief Intermittent Psychotic Syndrome

3.1. Severity rating of psychotic intensity (6) on any one of the 5 SIPS positive symptoms

3.2. Symptom is present at least several minutes per day at a frequency of at least once per month.

3.3. Symptom must have reached a psychotic intensity in the past 3 months 3.4. Symptom is not seriously disorganizing or dangerous 3.5. Symptom does not last for more than 1 hour per day at an average frequency of 4 days per week, over 1 month.

IMPROVING THE CLINICAL PREDICTION OF PSYCHOSIS BY COMBINING ULTRA HIGH RISK CRITERIA AND COGNITIVE BASIC SYMPTOMS

Cognitive impairments are regarded as a core component of Schizophrenia. Franke SchultzeLutter, Joachim Klosterkötter, Stephan Ruhrmann studied whether the combination of symptomatic UHR criteria and the basic symptom criterion “ cognitive disturbances” (COGDIS) is superior in predicting first episode psychosis [14].

Cognitive impairment as defined by deficient neurocognitiv test performance is integral to the development of psychosis and “impaired cognition” is one of the eight dimentions of psychotic symptom severity” proposed in DMS-V (APA, 2013). Yet, the cognitive dimension is not considered in ultra-high risk (UHR) criteria of psychosis [13].

BS concept refers to the idea that subjects may notice subtle changes which result from the disturbances in neural information processing that underlie the development of psychosis at very early stages, have been regarded as closely related to neurobiology [15].

Subsequenlty occurring APS and/or psychotic symptoms have been considered final psychopathological expressions or “ end phenomena”, which develop on the basis of dysfunctional or insufficient coping [15].

BS criteria are based predominantly on cognitive disturbances (COGDIS), predicts future psychosis well, independent of UHR [7,8].

COGDIS frequently co-occurs with symptomatic UHR criteria (APS and BLIPS) in at risk samples [5]. A combined UHR and BS approach may improve the prediction of psychosis [14].

The combination of symptomatic UHR criteria (mainly APS) and self- reported cognitive disturbance (COGDIS) indicate a higher risk for conversion to psychosis than the singular presence of either criterion.

Klosterkötter and Schultze-Lutter, 2009, proposed two-stage model of an “ early” and “late” at risk state, based on the BS concept [7,12,15].

Early stage is defined by the presence of the UHR trait-state criterion and or BS criteria and the absence of APS and BLIPS. The late stage is defined by APS and/or BLIPS irrespective of possible BS or trait-state criteria. In the third stage is frank psychosis [14].

In the clinical practice, the combination of APS with self-experienced changes in one’s normal mode of thinking (cognitive BS) might ameliorate difficulties reported in the identification of APS and BLIPS in children and adolescents: the role of fantasy and imaginary friends, peer group influences and/or the unclear interpretation of observable behavioral changes.

BS are subtle, subjectively experienced subclinical disturbances in drive, affect, thinking, speech, body perception, motor action, central vegetative functions and stress tolerance. They can occur and have been reported in every stage of the illness, ie, in the prodrome to the first psychotic episode, in prodroms to relapse, in residual states and even during psychotic episodes per se.

By definition, BS are different from what is considered to be one’s normal “mental” self. Being subjective, they remain predominantly private and apparent only to the affected person. They are rarely observable to others although a patient’s self-initiated coping strategies (including avoidance strategies and social withdrawal) in response to his/her BS may be recognizable to others. Being self-experiences, BS differ from negative symptoms as they are currently understood, ie, as functional deficits observable to others. BS are also distinct from frank psychotic symptoms that are experienced by the patient as real, normal thinking, and feeling. In contrast, BS are spontaneously and immediately recognized by the affected person as disturbances of his/her own (mental) processes. Insight that something is wrong with one’s thinking is present, yet some experiences might be so new and strange that they remain nearly inexplicable. The rare, highly introspective person may be able to articulate what is happening, but any detailed description of these experiences usually requires help in the form of guided questioning. The ability to experience BS with insight and to cope with them often attenuates with progressive illness and emerging psychotic symptoms but is restored upon remission. Thus, an evaluation of BS is often hindered by acute and/or prominent psychotic symptoms [14].

Cognitive and Perceptual Basic Symptoms Associated With Psychosis and Prototypic Selfobservations by Patients [15]

• Thought interference, ie, an intrusion of completely insignificant thoughts hindering concentration/ thinking (“I can’t help thinking about other things, which is very distracting.”)
• Thought perseveration, ie, an obsessive like repetition of insignificant thoughts or mental images (“I always have to mull over what I just said. I can’t stop thinking about what I might have said wrong or what I could have added although I really don’t think that anything was wrong with what I said.”)
• Thought pressure, ie, a self-reported “chaos” of unrelated thoughts (“If I am stressed out my mind gets chaotic and I have great problems thinking straight. Too many thoughts come up at once.”)
• Thought blockages either with or without intrusion of a new thought also includes a sudden loss of the thread or train of thoughts (“Sometimes my thoughts just stop, are suddenly gone, like being cut off.”)
• Disturbance of receptive language, ie, paralysis in the immediate comprehension of simple words/ sentences, either read or heard, that can result in giving up reading or avoiding conversations (“I often can’t get the meaning of common words when I am reading.”)
• Disturbance of expressive speech, ie, problems in producing appropriate words, sometimes also experienced as a reduction in active vocabulary (“Sometimes I think it must appear as if English were really my second language, like I don’t know English very well because I have difficulties expressing myself. I forget the words.”)
• Disturbances of abstract thinking, ie, an unusual basic symptom seen when asking the patient to explain sayings or idioms (“Sometimes I get puzzled if a certain object or event only stands as a metaphor for some more general, abstract or philosophical meaning.”)
• Inability to divide attention between simultaneous nondemanding tasks that each draw primarily upon a different sense that would not usually require a switching of attention (“Doing two things at once has become impossible even with the simplest things. I always have to concentrate on one thing at a time, like if I prepare a sandwich, I cannot do anything else, like watch a film.”)
• Captivation of attention by details of the visual field that catches and holds the look (“Sometimes an object really seems to stand out from the rest of what I see. My eyes then fix on it. It’s like being spellbound, even though I don’t want to look at it at all.”)
• Decreased ability to discriminate between perception and ideas, true memories and fantasies (“I thought about my grandparents. Then a weird thing happened: I couldn’t remember if knew my grandparents properly, if they were real or if they were just in my imagination. Did I know them, or had I made them up?”)
• Unstable ideas of reference with insight (“When I was listening to the radio the idea that the lyrics had some special meaning for me suddenly popped up into my head. Of course I knew straight away that it was just my imagination, a kind of weird thing. I did not have to think twice about it to know that.”)
• Derealization, ie, a decreased emotional and gestalt connection with the environment (“Sometimes, I feel disconnected from the world around me, like I’m under a glass cover.”)
• Visual or acoustic perceptual disturbances with insight. Unlike hallucinations or schizotypal perceptual distortions, basic symptom perceptual observations are not regarded as real but are immediately recognized as a sensory or subjective problem. The knowledge that the misperception, eg, a wrong coloring, distorted shape or changed sound quality/intensity, has no counterpart in the real world is immediate and unquestioned (“People suddenly seemed changed and had different hair colors.”).

CLINICAL CORELATIONS BETWEEN APS AND COGDIS

Mc Glashan and Hoffman proposed 2 kinds of correlation: earlier onset of the illness was associated with short duration of the prodrome, high risk of cronicity and prominent disorganization symptoms whereas later onset of the illness was linked to long prodrome duration, low risk of chronicity and predominantlty organized systematic and paranoid desilusions. Studies have showed three distinct categories of prodromes duration. Mc Glashan and Hoffman have discovered at some pacients a prodome duration of over ten years.

The captivation of attention by details had the highest weight in the long duration of groups. Such experiences were observed by Matussek and Conrad and were interpreted as a breakdown in the Gestalt perception. The frequently reported “ hypersensitivity to light or certain optic stimuli” in the long prodrome groups could be interpreted as an inappropriate focusing on certain general aspects of visual stimuli such as brightness.

Basic symptoms have mainly transient character and are perceived consciounsly. This capability to counsciously compensate for the self-experienced disturbances could explain the long duration of the prodrome in this group.

Selective attention is deficient, which is selfexperienced as hyperdistractibility. A decreased guidance of perception by stored memories could also account for the “changes in the perception of others” [16].

Thought pressure “ was a main psychopatological characteristic in the long duration group” . This pressure of unrelated thoughs is controlled consciously. The short duration group was described by disturbances of receptive language and of the perception of the intensity quality of acoustic simuli and derealization. In deralization, this may also include the affective dimension of past experiences necessary to make new perceptions feel familiar and real.

The disturbance of receptive language is defined as a self-reported often transient of partial difficulty to comprehend and recognize the meaning of common words, word sequences or sentences when reading or listening to others. This disturbance was a main characteristic of the short and medium duration group [16].

EPA GUIDANCE ON THE EARLY DETECTION OF CLINICAL HIGH RISK STATES OF PSYCHOSIS

Approximately 10-15% of all psychoses are early-onset psychoses (EOP) manifestating before the age of 18 and approximately 1-3% are very early onset psychoses. (VEOP) with an onset before the age of 13. Following psychotic episodes, negative symptoms commonly persist, and are associated with cognitive impairments and psychological disabilities [17].

The clinical high risk state (CHR) of psychosis

Currently, there are two complementary approaches to the characterization of the CHR state on psychoses: the ultra high risk (UHR) and the basic symptoms criteria [17].

Early detection of psychoses in children and adolescents

Since EOP were reported to present a slightly different onset and clinical picture compared to adult- onset psychoses, early detection in children and adolescents might be confronted with additional challenges. This is supported by first reports on conversion rates in adolescents risk samples between age 12 and 18, indicating that lag time to conversion might be longer and, consequently, conversion rates to the first years following initial risk assessment might be lower. Furthermore, recent studies reported high prevalence rates of attenuated psychotic symptoms, in particular of hallucinations, in children and young adolescents, which seem to decreas with age and to remit spontaneously in about three quarters of cases [17].

Recent studies have suggested that the combined assessment of UHR and BS criteria, especially COGDIS was advantageous to their exclusive assessment in identifying an CHR [17,18,19].

PROPOSED RECOMMANDATIONS OF THE EUROPEAN GUIDANCE PROJECT [17]

Reccomandation 1

• At least any one attenuated psychotic symptom:

1. unusual thought contents or delusional ideas not held with full conviction, including ideas of reference notimmediately rectified by cognition, 2. perceptual aberrations or hallucination with remaining insight, or 3.  disorganized communication or speech that is still comprehensible and responds to structuring in the interview that meets the additional requirements of either SIPS or early CAARMS

• At least any two self-experienced and selfreported cognitive basic symptoms rated irrespective of their appearance in the interview:

1. interference of completely insignificant thought contents,
   2. blockage of thoughts not explained by lack of concentration or attention,
2. thought pressure by thoughts unrelated to a common topic,

4,5.  disturbances of receptive or expressive speech in everyday use of native language,

6. inability to divide attention between tasks relating to different senses and generally not requiring full attention each such as making a sandwich and talking to someone,
7. disturbance in the immediate recognition and understanding of any kind of abstract, figurative or symbolic phrases or contents,
8. subjective experience of self-reference that are almost immediately rectified by cognition, and
9. captivation of attention by insignificant details of the visual field that impairs paying attention to more relevant stimuli) that have not been present in what the patient considers his/her premorbid stage, have occurred at least on a weekly basis for some time in the past 3 months and are not an effect of drug use; z

• At least any one transient psychotic symptom: delusion, hallucination, formal thought disorder) that meets the additional requirements of either SIPS or early CAARMS.

Recommendation 2

The EPA considers that a genetically increased risk of psychosis by a positive family history of psychosis in at least one first-degree biological relative should not be used as a clinical indicator of a CHR on its own, even if accompanied by functional deficits and mental problems. Rather, it should be regarded as a general risk factor indicating an already increased pre-CHR assessment risk for psychosis that should be taken into account in patients meeting the above CHR criteria. Patients not presenting the above CHR criteria but a genetic risk and other mental problems should however be encouraged to present again for a CHR assessment should they note the onset of mental problems resembling CHR symptoms.

Recommendation 3

The EPA considers that a significant decline in occupational and/or social functioning (and, relatedly, in productivity) should not be an obligate requirement in the above CHR criteria for the lack of evidence for an improvement of prediction by this addition. However, it should be considered as an indication of an imminence of risk of conversion and CHR patients with a significant functional decline should be considered at high need for treatment.

Recommendation 4

The EPA considers that the above CHR criteria should only be applied in persons already distressed by mental problems and seeking help for them or persons seeking clarification of their current risk for a vulnerability for psychosis, e.g., by genetic risk. Any clinical screening of other persons seems not warranted by current scientific evidence.

Recommendation 5

The EPA considers that the above CHR criteria should only be used and communicated with outmost care in children and young adolescents in whom they should nevertheless be assessed and monitored (Schmidt SJ et al). In late adolescence, however, the CHR criteria seem to be as applicable as in adults.

Recommendation 6

The EPA considers that a trained specialist (psychiatrist, clinical psychologist or equivalent mental health professional) with sufficient experience in CHR should carry out the assessment; if referral to a specialist is not possible, the responsible clinician should consult a trained specialist on the case, e.g. by phone; and specialized early detection services should be prepared to give such advice, e.g., within the framework of telephone consultation hours. Case conferences with experts in early detection of psychoses are even advised for mental health specialists.

Prodromal risk syndrome in psychoses is a transitional diagnosis that is utilized for a limited period of time, that will be replaced later on with another DSM-V diagnosis and has a similar evolution with Schizophreniform disorder and Non affective Psychoses.

The concept of transitional diagnoses has much in common with proposal for “ staging” psychotic illness” and proposal for considering a developmental perspective.

DSM-V diagnosis of Prodromal risk syndrome is supported by the evidence of validity presented here and by the patients’ current need for treatment in addition to the high probability of illness progression.

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