Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two‐year follow‐up

Prospective evaluation of youths with early psychotic‐like experiences can enrich our knowledge of clinical, biobehavioral and environmental risk and protective factors associated with the development of psychotic disorders. We aimed to investigate the predictors of persistence or worsening of psychosis spectrum features among US youth through the first large systematic study to evaluate subclinical symptoms in the community. Based on Time 1 screen of 9,498 youth (age 8‐21) from the Philadelphia Neurodevelopmental Cohort, a subsample of participants was enrolled based on the presence (N=249) or absence (N=254) of baseline psychosis spectrum symptoms, prior participation in neuroimaging, and current neuroimaging eligibility. They were invited to participate in a Time 2 assessment two years on average following Time 1. Participants were administered the Structured Interview for Prodromal Syndromes, conducted blind to initial screen status, along with the Schizotypal Personality Questionnaire and other clinical measures, computerized neurocognitive testing, and neuroimaging. Clinical and demographic predictors of symptom persistence were examined using logistic regression. At Time 2, psychosis spectrum features persisted or worsened in 51.4% of youths. Symptom persistence was predicted by higher severity of subclinical psychosis, lower global functioning, and prior psychiatric medication at baseline. Youths classified as having psychosis spectrum symptoms at baseline but not at follow‐up nonetheless exhibited comparatively higher symptom levels and lower functioning at both baseline and follow‐up than typically developing youths. In addition, psychosis spectrum features emerged in a small number of young people who previously had not reported significant symptoms but who had exhibited early clinical warning signs. Together, our findings indicate that varying courses of psychosis spectrum symptoms are evident early in US youth, supporting the importance of investigating psychosis risk as a dynamic developmental process. Neurocognition, brain structure and function, and genomics may be integrated with clinical data to provide early indices of symptom persistence and worsening in youths at risk for psychosis.     

Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

Prediction of psychosis across protocols and risk cohorts using automated language analysis

Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer‐based natural language processing analyses, we previously showed that, among English‐speaking clinical (e.g., ultra) high‐risk youths, baseline reduction in semantic coherence (the flow of meaning in speech) and in syntactic complexity could predict subsequent psychosis onset with high accuracy. Herein, we aimed to cross‐validate these automated linguistic analytic methods in a second larger risk cohort, also English‐speaking, and to discriminate speech in psychosis from normal speech. We identified an automated machine‐learning speech classifier – comprising decreased semantic coherence, greater variance in that coherence, and reduced usage of possessive pronouns – that had an 83% accuracy in predicting psychosis onset (intra‐protocol), a cross‐validated accuracy of 79% of psychosis onset prediction in the original risk cohort (cross‐protocol), and a 72% accuracy in discriminating the speech of recent‐onset psychosis patients from that of healthy individuals. The classifier was highly correlated with previously identified manual linguistic predictors. Our findings support the utility and validity of automated natural language processing methods to characterize disturbances in semantics and syntax across stages of psychotic disorder. The next steps will be to apply these methods in larger risk cohorts to further test reproducibility, also in languages other than English, and identify sources of variability. This technology has the potential to improve prediction of psychosis outcome among at‐risk youths and identify linguistic targets for remediation and preventive intervention. More broadly, automated linguistic analysis can be a powerful tool for diagnosis and treatment across neuropsychiatry.     

Psychosis as a transdiagnostic and extended phenotype in the general population

A large body of research indicates that weak expressions of positive psychotic symptoms (“psychotic experiences”) can be measured in the general population, and likely represent the behavioural manifestation of distributed multifactorial (genetic and non‐genetic) risk for psychosis. Psychotic experiences are a transdiagnostic phenomenon: the majority of individuals with these experiences have a diagnosis of non‐psychotic disorder, particularly common mental disorder, in which psychotic experiences predict greater illness severity and poorer treatment response. Some of the people with common mental disorder and psychotic experiences will present to mental health services meeting criteria for “clinical high risk”. Treatment of the transdiagnostic dimension of psychosis in individuals with common mental disorder who meet “clinical high risk” criteria thus may improve outcome (which cannot be interpreted as prevention of “schizophrenia”). Subthreshold psychotic experiences are transitory in about 80% of individuals, while around 20% go on to develop persistent psychotic experiences and 7% a psychotic disorder, with an annual transition rate of 0.5‐1%. Persistence is associated, on the one hand, with environmental exposures, particularly childhood trauma, and, on the other, with network‐type dynamic interactions between psychotic experiences themselves (e.g., interactions between hallucinatory experiences and delusional ideation) and between symptom dimensions (e.g., interactions between affective symptoms and psychotic experiences, or interactions between subthreshold negative symptoms and psychotic experiences). The study of psychotic experiences is helping to elucidate the mechanisms by which environmental and genetic influences shape the transdiagnostic expression of psychosis proneness, that is mostly transitory but may first become persistent over time and eventually give rise to transition to a psychotic disorder.     

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

Clinical,socio‐demographic and psychological characteristics in individuals with persistent psychotic experiences with and without a “need for care”

Individuals reporting persistent psychotic experiences (PEs) in the general population, but without a “need for care”, are a unique group of particular importance in identifying risk and protective factors for psychosis. We compared people with persistent PEs and no “need for care” (non‐clinical, N=92) with patients diagnosed with a psychotic disorder (clinical, N=84) and controls without PEs (N=83), in terms of their phenomenological, socio‐demographic and psychological features. The 259 participants were recruited from one urban and one rural area in the UK, as part of the UNIQUE (Unusual Experiences Enquiry) study. Results showed that the non‐clinical group experienced hallucinations in all modalities as well as first‐rank symptoms, with an earlier age of onset than in the clinical group. Somatic/tactile hallucinations were more frequent than in the clinical group, while commenting and conversing voices were rare. Participants in the non‐clinical group were differentiated from their clinical counterparts by being less paranoid and deluded, apart from ideas of reference, and having fewer cognitive difficulties and negative symptoms. Unlike the clinical group, they were characterized neither by low psychosocial functioning nor by social adversity. However, childhood trauma featured in both groups. They were similar to the controls in psychological characteristics: they did not report current emotional problems, had intact self‐esteem, displayed healthy schemas about the self and others, showed high life satisfaction and well‐being, and high mindfulness. These findings support biopsychosocial models postulating that environmental and psychological factors interact with biological processes in the aetiology of psychosis. While some PEs may be more malign than others, lower levels of social and environmental adversity, combined with protective factors such as intact IQ, spirituality, and psychological and emotional well‐being, may reduce the likelihood of persistent PEs leading to pathological outcomes. Future research should focus on protective factors and determinants of well‐being in the context of PEs, rather than exclusively on risk factors and biomarkers of disease states.     

Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio‐economic development of the country or the specific health care system.     

20-year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the OPUS study

This study aimed to identify the 20-year trajectories of positive and negative symptoms after the first psychotic episode in a sample of patients with an ICD-10 diagnosis of schizophrenia spectrum disorder, and to investigate the baseline characteristics and long-term outcomes associated with these trajectories. A total of 373 participants in the OPUS trial were included in the study. Symptoms were assessed at baseline and after 1, 2, 5, 10 and 20 years using the Scales for the Assessment of Positive and Negative Symptoms. We used latent class growth mixture modelling to identify trajectories, and multinominal regression analyses to investigate predictors of membership to identified trajectories. Five trajectories of positive symptoms were identified: early continuous remission (50.9% of the sample), stable improvement (18.0%), intermittent symptoms (10.2%), relapse with moderate symptoms (11.9%), and continuous severe symptoms (9.1%). Substance use disorder (odds ratio, OR: 2.83, 95% CI: 1.09-7.38, p=0.033), longer duration of untreated psychosis (OR: 1.02, 95% CI: 1.00-1.03, p=0.007) and higher level of negative symptoms (OR: 1.60, 95% CI: 1.07-2.39, p=0.021) were predictors of the relapse with moderate symptoms trajectory, while only longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.030) predicted membership to the continuous severe symptoms trajectory. Two trajectories of negative symptoms were identified: symptom remission (51.0%) and continuous symptoms (49.0%). Predictors of the continuous symptoms trajectory were male sex (OR: 3.03, 95% CI: 1.48-6.02, p=0.002) and longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.034). Trajectories displaying continuous positive and negative symptoms were linked to lower neurocognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) (z-score: –0.78, CI: –1.39 to –0.17, for continuous positive symptoms; z-score: –0.33, CI: –0.53 to –0.13, for continuous negative symptoms). The same trajectories were also linked to higher use of antipsychotic medication at 20-year follow-up (continuous positive symptoms: 78%; continuous negative symptoms: 67%). These findings suggest that the majority of patients with first-episode schizophrenia spectrum disorder have a trajectory with early stable remission of positive symptoms. Long duration of untreated psychosis and comorbid substance abuse are modifiable predictors of poor trajectories for positive symptoms in these patients. In about half of patients, negative symptoms do not improve over time. These symptoms, in addition to being associated with poor social and neurocognitive functioning, may prevent patients from seeking help.     

Facial and Prosodic Emotion Recognition Deficits Associate with Specific Clusters of Psychotic Symptoms in Schizophrenia

Background

Patients with schizophrenia perform significantly worse on emotion recognition tasks than healthy participants across several sensory modalities. Emotion recognition abilities are correlated with the severity of clinical symptoms, particularly negative symptoms. However, the relationships between specific deficits of emotion recognition across sensory modalities and the presentation of psychotic symptoms remain unclear. The current study aims to explore how emotion recognition ability across modalities and neurocognitive function correlate with clusters of psychotic symptoms in patients with schizophrenia.

Methods

111 participants who met the DSM-IV diagnostic criteria for schizophrenia and 70 healthy participants performed on a dual-modality emotion recognition task, the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and selected subscales of WAIS-III. Of all, 92 patients received neurocognitive evaluations, including CPT and WCST. These patients also received the PANSS for clinical evaluation of symptomatology.

Results

The emotion recognition ability of patients with schizophrenia was significantly worse than healthy participants in both facial and vocal modalities, particularly fearful emotion. An inverse correlation was noted between PANSS total score and recognition accuracy for happy emotion. The difficulty of happy emotion recognition and earlier age of onset, together with the perseveration error in WCST predicted total PANSS score. Furthermore, accuracy of happy emotion and the age of onset were the only two significant predictors of delusion/hallucination. All the associations with happy emotion recognition primarily concerned happy prosody.

Discussion

Deficits in emotional processing in specific categories, i.e. in happy emotion, together with deficit in executive function, may reflect dysfunction of brain systems underlying severity of psychotic symptoms, in particular the positive dimension.     

What causes psychosis? An umbrella review of risk and protective factors

Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta‐analyses of observational studies which examined associations between socio‐demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017. The literature search and data extraction followed PRISMA and MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of non‐organic psychotic disorders was graded into convincing, highly suggestive, suggestive, weak, or non‐significant according to a standardized classification based on: number of psychotic cases, random‐effects p value, largest study 95% confidence interval, heterogeneity between studies, 95% prediction interval, small study effect, and excess significance bias. In order to assess evidence for temporality of association, we also conducted sensitivity analyses restricted to data from prospective studies. Fifty‐five meta‐analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra‐high‐risk state for psychosis (odds ratio, OR=9.32, 95% CI: 4.91‐17.72) and Black‐Caribbean ethnicity in England (OR=4.87, 95% CI: 3.96‐6.00) showed convincing evidence of association. Six factors were highly suggestive (ethnic minority in low ethnic density area, second generation immigrants, trait anhedonia, premorbid IQ, minor physical anomalies, and olfactory identification ability), and nine were suggestive (urbanicity, ethnic minority in high ethnic density area, first generation immigrants, North‐African immigrants in Europe, winter/spring season of birth in Northern hemisphere, childhood social withdrawal, childhood trauma, Toxoplasma gondii IgG, and non‐right handedness). When only prospective studies were considered, the evidence was convincing for ultra‐high‐risk state and suggestive for urbanicity only. In summary, this umbrella review found several factors to be associated with psychotic disorders with different levels of evidence. These risk or protective factors represent a starting point for further etiopathological research and for the improvement of the prediction of psychosis.     

Transdiagnostic dimensions of psychosis in the Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIP)

The validity of the classification of non‐affective and affective psychoses as distinct entities has been disputed, but, despite calls for alternative approaches to defining psychosis syndromes, there is a dearth of empirical efforts to identify transdiagnostic phenotypes of psychosis. We aimed to investigate the validity and utility of general and specific symptom dimensions of psychosis cutting across schizophrenia, schizoaffective disorder and bipolar I disorder with psychosis. Multidimensional item‐response modeling was conducted on symptom ratings of the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Montgomery‐Åsberg Depression Rating Scale in the multicentre Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIP) consortium, which included 933 patients with a diagnosis of schizophrenia (N=397), schizoaffective disorder (N=224), or bipolar I disorder with psychosis (N=312). A bifactor model with one general symptom dimension, two distinct dimensions of non‐affective and affective psychosis, and five specific symptom dimensions of positive, negative, disorganized, manic and depressive symptoms provided the best model fit. There was further evidence on the utility of symptom dimensions for predicting B‐SNIP psychosis biotypes with greater accuracy than categorical DSM diagnoses. General, positive, negative and disorganized symptom dimension scores were higher in African American vs. Caucasian patients. Symptom dimensions accurately classified patients into categorical DSM diagnoses. This study provides evidence on the validity and utility of transdiagnostic symptom dimensions of psychosis that transcend traditional diagnostic boundaries of psychotic disorders. Findings further show promising avenues for research at the interface of dimensional psychopathological phenotypes and basic neurobiological dimensions of psychopathology.     

Neuropsychological Impairment in Prodromal,First-Episode,and Chronic Psychosis: Assessing RBANS Performance

BackgroundCognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis.MethodWe administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis.ResultsPerformance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis.ConclusionsCognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio‐demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 ± 17.6 months after initial assessment. Eighty‐nine participants with 22q11DS (age range: 8‐30 years; mean 16.1 ± 4.7) were assessed using the Structured Interview for Psychosis‐Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non‐UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high‐risk samples. Nevertheless, the relatively high transition rate in non‐UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.     

Investigating civic participation developmental trajectories among Canadian youths transitioning into adulthood

Current knowledge of intraindividual longitudinal patterns of civic participation (CP) and their predictors remains limited. As life cycle trends are showing a decline in civic/political involvement during early adulthood years, increased understanding of these aspects could enhance efforts to promote greater and/or sustained CP trajectories among youth transitioning into adulthood. The current study aimed to identify youths CP developmental trajectories from age 18 to 22 and examine their predictors in late adolescence. The four following CP trajectories were identified among 327 Canadian youths (61% Female; 90% Caucasian; 100% French-speaking) through semiparametric modeling: Low with slight decline (56.9%), Moderate sustained (25.1%), High with steep decline (12.5%), and High sustained (5.5%). Youths displaying higher academic performance, civic attitudes, altruistic orientation, prosocial/community-oriented, and academic/vocational activity involvement were more likely to be assigned to higher at baseline and/or sustained CP trajectories. Implementing youths CP promotional programs targeting these attributes may hold promise for addressing issues sustaining CP in youths transitioning into adulthood.     

Childhood Psychosis or Mental Retardation: A Diagnostic Dilemma: I. Psychiatric and Psychological Aspects

A relatively large percentage of children seen at a mental retardation clinic demonstrated psychotic symptoms. The entire group with psychotic manifestations, 62 in all, were reviewed in order to clarify the diagnosis of childhood psychosis or mental retardation. The 1961 British criteria for childhood psychosis were used and are advocated by the authors. Childhood psychosis was the primary diagnosis in 38 cases, and psychosis secondary to brain damage in 24 cases. Onset of the condition under the age of three years and a poor prognosis for social recovery were characteristic of the entire group.Obvious emotional disorder was present in 21 mothers and 14 fathers. There was a continuum in terms of number of psychotic symptoms, level of intelligence and presence of organic signs. It is concluded that there is an overlap between the entities of childhood psychosis and mental retardation.     

The Psychosis Recent Onset GRoningen Survey (PROGR-S): Defining Dimensions and Improving Outcomes in Early Psychosis

Psychotic disorders are among the most complex medical conditions. Longitudinal cohort studies may offer further insight into determinants of functional outcome after a psychotic episode. This paper describes the Psychosis Recent Onset in GRoningen Survey (PROGR-S) that currently contains data on 1076 early-episode patients with psychosis, including symptoms, personality, cognition, life events and other outcome determinants. Our goal in this report is to give an overview of PROGR-S, as a point of reference for future publications on the effect of cognition, personality and psychosocial functioning on outcomes. PROGR-S contains an extensive, diagnostic battery including anamnesis, biography, socio-demographic characteristics, clinical status, drug use, neuropsychological assessment, personality questionnaires, and physical status tests. Extensive follow-up data is available on psychopathology, physical condition, medication use, and care consumption. Sample characteristics were determined and related to existing literature. PROGR-S (period 1997–2009, n = 718) included the majority of the expected referrals in the catchment area. The average age was 27 (SD = 8.6) and two-thirds were male. The average IQ was lower than that in the healthy control group. The majority had been diagnosed with a psychotic spectrum disorder. A substantial number of the patients had depressive symptoms (479/718, 78%) and current cannabis or alcohol use (465/718, 75%). The level of community functioning was moderate, i.e. most patients were not in a relationship and were unemployed. The PROGR-S database contains a valuable cohort to study a range of aspects related to symptomatic and functional outcomes of recent onset psychosis, which may play a role in the treatment of this complex and disabling disorder. Results reported here show interesting starting points for future research. Thus, we aim to investigate long-term outcomes on the basis of cognition, personality, negative symptoms and physical health. Ultimately, we hope that this paper will contribute improving the health of patients with psychotic disorders.     

Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and es­timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.