Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume.

BACKGROUND: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. METHODS: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. RESULTS: We found no association, only a trend, between PSRS and white matter volume over all groups (ß = 0.24, p = 0.07, 95% confidence interval = [-0.02 - 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (ß = 0.70, p = 0.02, 95% confidence interval = [0.14 - 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. CONCLUSION: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.

Age-related brain structural alterations as an intermediate phenotype of psychosis.

BACKGROUND: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. METHODS: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. RESULTS: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. LIMITATIONS: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. CONCLUSION: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis.

BACKGROUND: Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. METHODS: We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. RESULTS: The model including reward-induced modulation of insula-ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula-ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula-ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. LIMITATIONS: The modest sample size of untreated patients with FEP was a limitation of our study. CONCLUSION: This study indicates that insula-ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction.

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology.

BACKGROUND/AIMS: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). METHODS: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. RESULTS: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. CONCLUSION: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.

Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state.

BACKGROUND: Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes. METHODS: Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling. RESULTS: Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory-induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score. LIMITATIONS: The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis. CONCLUSION: This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology.

Cenesthopathy in adolescence: an appraisal of diagnostic overlaps along the anxiety-hypochondriasis-psychosis spectrum.

OBJECTIVE: To discuss the diagnostic validity of unusual bodily perceptions along the spectrum from age-specific, often transitory and normal, to pathological phenomena in adolescence to hypochondriasis and finally to psychosis. METHODS: Critical literature review of the cornerstone diagnostic groups along the spectrum embracing anxiety and cenesthopathy in adolescence, hypochondriasis, and cenesthopathy and psychosis, followed by a discussion of the diagnostic overlaps along this spectrum. RESULTS: The review highlights significant overlaps between the diagnostic cornerstones. It is apparent that adolescents with unusual bodily perceptions may conceptually qualify for more than one diagnostic group along the spectrum. To determine whether cenesthopathies in adolescence mirror emerging psychosis, a number of issues need to be considered, i.e. age and mode of onset, gender, level of functioning and drug use. The role of overvalued ideas at the border between hypochondriasis and psychosis must be considered. CONCLUSION: As unusual bodily symptoms may in some instances meet formal psychosis risk criteria, a narrow understanding of these symptoms may lead to both inappropriate application of the new DSM-5 attenuated psychosis syndrome and of treatment selection. On the other hand, the possibility of a psychotic dimension of unusual bodily symptoms in adolescents must always be considered as most severe expression of the cenesthopathy spectrum.

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study.

OBJECTIVES: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS). EXPERIMENTAL DESIGN: Patients with "first-episode psychosis" (FEP, n = 21), short-term ARMS (ARMS-ST, n = 17), long-term ARMS (ARMS-LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n-back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. PRINCIPAL OBSERVATIONS: There were no differences in accuracy, but the FEP and the ARMS-ST group had longer reaction times compared with the HC and the ARMS-LT group. With the 2-back > 0-back contrast, we found reduced functional activation in ARMS-ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS-LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS-LT, the ARMS-ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS-LT group. CONCLUSIONS: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto-temporo-parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors.

Cannabis-induced depersonalization disorder in adolescence.

We present a case series of 6 patients who developed persistent depersonalization disorder in adolescence after consuming cannabis. In 2 of these cases, the illness course was severely disabling. Within the growing body of literature that investigates the effects of cannabis use on mental health, the association between cannabis and depersonalization disorder is widely neglected. We review the clinical characteristics of this disorder and summarize the neurobiological evidence relating it to cannabis use. This case series extends awareness about the potentially detrimental effect of cannabis use in young individuals beyond its well-documented relationship with psychosis and other psychological sequelae.

Commentary about social avoidance and its significance in adolescents and young adults.

Social avoidance in young patients is a clinically worrisome phenomenon that characterizes impending schizophrenia, but that also constitutes a core phenomenon in avoidant personality disorder (AvPD), schizoid personality disorder (ScPD), and in autism spectrum disorder (ASD). Especially in the absence of any other clinically relevant phenomena, understanding the origins of social avoidance may be one the most challenging tasks in assessing whether adolescents and young adults are at risk for developing schizophrenia. Descriptive and psychometric assessments only allow to comment on the absence or the presence of this phenomenon, but do not capture the origins and the meaning of social avoidance. Based on a narrative review, we highlight the importance of a phenomenological approach to unveil the Gestalt of social avoidance in these mental disorders, including and appraisal of the underlying mental structures and attachment styles. The phenomenological approach allows to distinguish the Gestalt of social avoidance between AvPD, ScPD, ASD, and beginning schizophrenia, to ensure correct diagnostic labelling and optimal treatment, and to avoid unwarranted stigmatization.

Subclinical hallucinations in adolescent outpatients: an outcome study.

OBJECTIVE: We assessed the continued prevalence at one year and association with clinical variables of subclinical hallucinations ascertained at baseline in a cohort of adolescent outpatients referred to a specialized early psychosis service. We further assessed the prevalence of psychiatric disorders in adolescents presenting subclinical hallucinations. METHOD: 84 adolescent patients were sampled from a longitudinal, prospective study that assesses the course of clinical and neuropsychological measures in patients identified as at high clinical risk for psychosis. Subclinical hallucinations were measured using the Scale of Prodromal Symptoms (SOPS) with its companion interview manual (Structured Interview for Prodromal Symptoms, SIPS) [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatr. Q. 70, 273-287; McGlashan, T.H., Miller, T.J., Woods, S.W., Rosen, J.L., Hoffman, R.E., Davidson, L., 2001. Structured Interview for Prodromal Syndromes (Version 3.0, unpublished manuscript). PRIME Research Clinic, Yale School of Medicine New Haven, Connecticut. ], and the Schizophrenia Proneness Instrument -Adult Version (SPI-A) [Schultze-Lutter, F., Addington, J., Ruhrmann, S., Klosterkötter, J., 2007. Schizophrenia Proneness Instrument (SPI-A). Giovanni Fioriti, Rome, Italy]. At one-year follow-up, only patients reporting subclinical hallucinations at initial assessment were studied. RESULTS: Full remission of subclinical hallucinations occurred in over half and at least partial remission in two thirds of these patients at one-year follow-up. Mood disorders were present in 62.5% of adolescents with subclinical hallucinations at initial assessment. SOPS measures for depression, deficient attention and for unusual/delusional thought were significantly associated with subclinical hallucinations at baseline. However, sustained experience of subclinical hallucinations at one-year follow-up was only predicted by the global level of functioning at baseline, while cannabis abuse, psychiatric and psychopharmacological treatment were not predictors. CONCLUSIONS: Subclinical hallucinations occur across a wide range of mental states in adolescents and show high rates of remission. Our results warrant that the clinical meaning of such phenomena needs to be carefully weighed against the specific developmental phenomena in this particular age range.

The International Study on General Practitioners and Early Psychosis (IGPS).

BACKGROUND: In much of the world, general practitioners (GPs) are the health professionals most frequently initially contacted when a young person is developing psychosis. However little is known about their expertise in assessing psychosis and its risk. METHODS: To assess the diagnostic patterns and treatment practices related to psychosis of GPs working in a range of health care systems, questionnaires were mailed to 12,516 randomly selected GPs in seven countries: Canada, Australia, New Zealand, England, Norway, Austria and the Czech Republic. Sites were defined as gatekeeping or non-gatekeeping, based on the primary care health system in effect at each site. A gatekeeping system (GK) is one which mandates that patients see a GP before in order to be referred to a specialist. By contrast, in a non-gatekeeping (nGK) system, individuals can seek help directly from specialists without authorization by a GP. RESULTS: Twenty-two percent (n=2784) GPs responded to the mailed questionnaire. They reported low prevalence of early psychosis seen in general practice. Using awareness of functional decline as a prognostic sign as a proxy, gatekeeping (GK) GPs were found to be superior in their knowledge of the signs and symptoms of early psychosis than were non-gatekeeping GPs. GP's with less knowledge as to early psychosis were more likely to refer individuals with suspected psychosis to specialists. GP's reported a preference for access to specialized outpatient services as compared with obtaining continuous medical education relevant to early psychosis. The duration of maintenance treatment recommended by GP's was less than that recommended in international guidelines. GP's also underestimated the risk for relapse after a first episode of psychosis. CONCLUSIONS: As GPs were largely unaware of features of early psychosis, such as functional decline, this should be the target of educational programs for GP's. However, the incidence of psychosis is low and GP's express a preference for access to appropriate referral over continuing medical education. Therefore, the development of specialized services for the assessment and care of patients who are in the early stages of developing schizophrenia may be warranted.

Clinical and functional ultra-long-term outcome of patients with a clinical high risk (CHR) for psychosis.

BACKGROUND: Few studies have followed up patients with a clinical high risk (CHR) for psychosis for more than 2-3 years. We aimed to investigate the rates and baseline predictors for remission from CHR and transition to psychosis over a follow-up period of up to 16 years. Additionally, we examined the clinical and functional long-term outcome of CHR patients who did not transition. METHODS: We analyzed the long-term course of CHR patients that had been included in the longitudinal studies "Früherkennung von Psychosen" (FePsy) or "Bruderholz" (BHS). Those patients who had not transitioned to psychosis during the initial follow-up periods (2/5 years), were invited for additional follow-ups. RESULTS: Originally, 255 CHR patients had been included. Of these, 47 had transitioned to psychosis during the initial follow-ups. Thus, 208 were contacted for the long-term follow-up, of which 72 (34.6%) participated. From the original sample of 255, 26%, 31%, 35%, and 38% were estimated to have transitioned after 3, 5, 10, and 16 years, respectively, and 51% had remitted from their high risk status at the latest follow-up. Better psychosocial functioning at baseline was associated with a higher rate of remission. Of the 72 CHR patients re-assessed at long-term follow-up, 60 had not transitioned, but only 28% of those were fully recovered clinically and functionally. CONCLUSIONS: Our study shows the need for follow-ups and clinical attention longer than the usual 2-3 years as there are several CHR patients with later transitions and only a minority of CHR those without transition fully recovers.

Deficient associative learning in drug-naive first-episode schizophrenia: results obtained using a new visual within-subjects learned irrelevance paradigm.

One of the key features of schizophrenia is the inability to filter out irrelevant stimuli which consequently leads to stimulus overload. There are different methods which aim at investigating these deficient filter mechanisms; one of these is the learned irrelevance (LIrr) paradigm. LIrr refers to the retardation of associative learning that occurs if the conditioned stimulus (CS) and the unconditioned stimulus (US) are preexposed in an explicitly unpaired manner prior to the establishment of the association between the stimuli. In the present study we used a recently developed computerized within-subject visual LIrr test. We measured 11 drug-naive first-episode schizophrenia patients and compared their performance to that of 17 healthy control subjects. LIrr was observed to be intact in normal individuals but disrupted in drug-naive first-episode schizophrenia patients. After one month elapsed, 5 of the 11 patients and 16 of the 17 control subjects were retested in a follow-up study. By this time, patients had been medicated with antipsychotic drugs for at least 3 weeks. While healthy controls exhibited a robust LIrr effect, patients still failed to show LIrr. Correlations were found between the performance of unmedicated patients and the depression component of the PANSS psychopathology scale.

First-episode 'coenesthetic' schizophrenia presenting with alien hand syndrome and partial agenesis of the corpus callosum.

We describe the case of a 23-year-old Caucasian woman who presented with alien hand syndrome and a first episode of the coenesthetic subtype of schizophrenia. 'Alienness' of her non-dominant hand was intimately phenomenologically associated with the onset of first-psychosis. Cerebral MRI revealed a partial agenesis of the corpus callosum with a complete absence of the rostrum, hypoplastic anterior and inferior genu, and a hypoplastic splenium. This case suggests that this syndrome can occur with the development of a functional disconnection syndrome involving the anterior callosum, and in this case the 'second hit' proposed to occur in early adulthood in schizophrenia may have interacted with her earlier neurodevelopmental lesion to result in a combination of psychosis and alien hand syndrome.

Early detection of psychosis: helpful or stigmatizing experience? A qualitative study.

AIM: Despite the large scientific debate concerning potential stigmatizing effects of identifying an individual as being in an at-risk mental state (ARMS) for psychosis, studies investigating this topic from the subjective perspective of patients are rare. This study assesses whether ARMS individuals experience stigmatization and to what extent being informed about the ARMS is experienced as helpful or harmful. METHODS: Eleven ARMS individuals, currently participating in the follow-up assessments of the prospective Basel Früherkennung von Psychosen (FePsy; English: Early Detection of Psychosis) study, were interviewed in detail using a semistructured qualitative interview developed for this purpose. Data were analysed using Interpretative Phenomenological Analysis. RESULTS: Most individuals experiencing first symptoms reported sensing that there was 'something wrong with them' and felt in need of help. They were relieved that a specific term was assigned to their symptoms. The support received from the early detection centre was generally experienced as helpful. Many patients reported stigmatization and discrimination that appeared to be the result of altered behaviour and social withdrawal due to the prepsychotic symptoms they experienced prior to contact with the early detection clinic. CONCLUSIONS: The results suggest that early detection services help individuals cope with symptoms and potential stigmatization rather than enhancing or causing the latter. More emphasis should be put on the subjective experiences of those concerned when debating the advantages and disadvantages of early detection with regard to stigma. There was no evidence for increased perceived stigma and discrimination as a result of receiving information about the ARMS.

Sexually dimorphic subcortical brain volumes in emerging psychosis.

BACKGROUND: In schizophrenic psychoses, the normal sexual dimorphism of the brain has been shown to be disrupted or even reversed. Little is known, however, at what time point in emerging psychosis this occurs. We have therefore examined, if these alterations are already present in the at-risk mental state (ARMS) for psychosis and in first episode psychosis (FEP) patients. METHODS: Data from 65 ARMS (48 (73.8%) male; age=25.1±6.32) and 50 FEP (37 (74%) male; age=27±6.56) patients were compared to those of 70 healthy controls (HC; 27 (38.6%) male; age=26±4.97). Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging (MRI) scanner. Linear mixed effects models were used to investigate whether subcortical brain volumes are dependent on sex. RESULTS: We found men to have larger total brain volumes (p<0.001), and smaller bilateral caudate (p=0.008) and hippocampus volume (p<0.001) than women across all three groups. Older subjects had more GM and WM volume than younger subjects. No significant sex×group interaction was found. CONCLUSIONS: In emerging psychosis there still seem to exist patterns of normal sexual dimorphism in total brain and caudate volume. The only structure affected by reversed sexual dimorphism was the hippocampus, with women showing larger volumes than men even in HC. Thus, we conclude that subcortical volumes may not be primarily affected by disrupted sexual dimorphism in emerging psychosis.

Repeated measurements of learned irrelevance by a novel within-subject paradigm in humans.

Learned irrelevance (LIrr) refers to the retardation of classical conditioning following preexposure of the to-be-associated stimuli. Healthy volunteers have been tested on three occasions with a new LIrr paradigm avoiding methodological problems which afflict traditional paradigms. A significant LIrr effect was demonstrated on each occasion. Thus, the new paradigm enables repeated measurements of LIrr and might be useful in evaluating long-term effects of medication in psychiatric disorders exhibiting aberrant LIrr.

Cognitive functioning in the schizophrenia prodrome.

In the last decade, there has been an increasing interest in cognitive alterations during the early course of schizophrenia. From a clinical perspective, a better understanding of cognitive functioning in putative at-risk states for schizophrenia is essential for developing optimal early intervention models. Two approaches have more recently been combined to assess the entire course of the initial schizophrenia prodrome: the predictive "basic symptom at-risk" (BS) and the ultra high-risk (UHR) criteria. Basic symptoms are considered to be present during the entire disease progression, including the initial prodrome, while the onset of symptoms captured by the UHR criteria expresses further disease progression toward frank psychosis. The present study investigated the cognitive functioning in 93 subjects who met either BS or UHR criteria and thus were assumed to be at different points on the putative trajectory to psychosis. We compared them with 43 patients with a first episode of psychosis and to 49 help-seeking patient controls. All groups performed significantly below normative values. Both at-risk groups performed at intermediate levels between the first-episode (FE) group and normative values. The UHR group demonstrated intermediate performance between the FE and BS groups. Overall, auditory working memory, verbal fluency/processing speed, and declarative verbal memory were impaired the most. Our results suggest that cognitive impairments may still be modest in the early stages of the initial schizophrenia prodrome and thus support current efforts to intervene in the early course of impending schizophrenia because early intervention may prevent or delay the onset of frank psychosis and thus prevent further cognitive damage.

[On the front line: survey on shared responsibility. General practitioners and schizophrenia]. / Sur la première ligne: sondage pour un partage. Les omnipraticiens et la schizophrénie.

CONTEXT: General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. OBJECTIVES: Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. METHODOLOGY: A postal survey was conducted with Quebec GPs who were randomly chosen. RESULTS: A total of 1003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. CONCLUSION: some of this survey's data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.

Defining subjects at risk for psychosis: a comparison of two approaches.

The ability to detect individuals at high risk for developing schizophrenia before they express the disease will lead to targeted early intervention. It has been proposed that subjects at risk share a core deficit with people who already have schizophrenia. This includes cognitive impairment, affective symptoms, social isolation and decline in social functioning. In a sample of 104 help-seeking patients from a specialised outpatient clinic we investigated how well two different sets of criteria define the at-risk group and capture this core deficit. One set of criteria is the well-established ultra high-risk model of McGlashan et al. [McGlashan 2001 (SIPS) McGlashan, T. H., Miller, T. J., Woods, S. W., et al. (2001) Structured Interview for Prodromal Syndromes (Version 3.0, unpublished manuscript). New Haven, Connecticut: PRIME Research Clinic, Yale School of Medicine.]; the other criteria were those defined by Cornblatt et al. [Cornblatt, B., Lencz, T., Smith, C.W., Correll, C.U., Auther, A., Nakayama, E., 2003. The schizophrenia prodrome revisited: a neurodevelopmental perspective. Schizophr. Bull. 29, 633-651.]. There was considerable overlap in the two sets of criteria. However, when the basic symptoms of Klosterkötter [Klosterkötter, J., Hellmich, M., Steinmeyer, E.M., Schultze-Lutter, F., 2001a. Diagnosing schizophrenia in the initial prodromal phase. Arch. Gen. Psychiatry, 58, 158-164.] were included in the McGlashan et al. model, a more narrow and homogeneous group was defined.