Cognitive Behavioral Therapy for Prodromal Stage of Psychosis—Outcomes for Transition,Functioning, Distress,and Quality of Life: A Systematic Review and Meta-analysis

ObjectiveThis study aimed to provide insight into the efficacy of cognitive-behavioral therapy for psychosis (CBTp) in patients with “clinical high risk of psychosis (CHR-P)”.MethodsMajor scientific databases were searched up to April 17, 2020. Randomized controlled trials in CHR-P individuals, comparing CBTp with needs-based interventions (NBI, including treatment as usual or nonspecific control treatment) were included, following PRISMA guidelines. The primary outcome (efficacy) was transition to psychosis by 6 months, 12 months, 24 months, and over 24 months. Secondary outcomes were change in attenuated psychotic symptoms, depression, distress, improvements in functioning, and quality of life.ResultsTen randomized controlled studies met inclusion criteria. The comparisons included 1128 participants. CBTp was significantly more efficacious in reducing rate of transition to psychosis by 6 months (after post-hoc sensitivity analysis) (relative risk [RR] = 0.44, 95% confidence interval [CI]: 0.26, 0.73), 12 months (RR = 0.44, 95% CI: 0.30, 0.64), 12 months (RR = 0.46, 95%CI: 0.30, 0.69), and over 24 months (RR = 0.58, 95% CI: 0.35, 0.95) after treatment, compared with those receiving NBI. CBTp was also associated with more reduced attenuated psychotic symptoms by 12 months (SMD = −0.17, 95% CI: −0.33, −0.02) and by 24 months (SMD = −0.24, 95% CI: −0.43, −0.06). No beneficial effects on functioning, depression, quality of life, or distress were observed favoring CBTp.ConclusionsCBTp is effective in reducing both psychosis transition rates and attenuated psychotic symptoms for the prodromal stage of psychosis. It is a promising intervention at the preventative stage.     

Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

BackgroundIndividuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.Methods“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.ResultsNinety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).ConclusionsThere is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.     

A developmentally-stable pattern of premorbid schizoid-schizotypal features predicts psychotic transition from the clinical high-risk for psychosis state

BackgroundDespite the extensive research performed on prediction of psychosis from a Clinical High Risk for Psychosis state (CHR-P), the positive predictive value of the CHR-P designation remains unsatisfactory and further models including additional clinical and biological variables are required. Existing studies indicate that schizotypy assessed at baseline in “at-risk” individuals may be considered a predictor of transition from CHR-P to psychosis. This approach, however, is burdened with bias resulting from a possible overlap between current psychopathology and schizotypal features. No studies so far have assessed schizotypy in CHR-P from a developmental perspective.AimThe aim of the study was to identify associations between a long-standing, parent-reported premorbid level of schizoid-schizotypal traits and the probability of psychotic transition in individuals with CHR-P.MethodsThe mothers of 107 individuals diagnosed as presenting CHR-P with the use of Comprehensive Assessment of At Risk Mental States12/2006 were interviewed with the Scale for the Assessment of Premorbid Schizoid-Schizotypal Traits (PSST).ResultsA high level of enduring schizotypy was found to be significantly associated with psychotic transition from CHR-P (HR: 1.78, 95% CI: 1.40–2.27, p < 0.0001), as indicated by the proportional hazards model, adjusted for age, sex and clinical covariates potentially related to the outcome. PSST items comprising negative schizotypy appeared to be the strongest predictors of transition.ConclusionsThe assessment of parent-reported, present early in the development premorbid schizoid-schizotypal traits, which can be easily performed in clinical settings, may be of value in estimating the probability of transition from an “at risk” state to psychotic disorder.     

Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study

Background and HypothesisMachine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs).Study DesignTotal 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat.Study ResultsThe accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%).ConclusionWe built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.     

The Epidemiology and Associated Phenomenology of Formal Thought Disorder: A Systematic Review

Background: Authors of the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) have recommended to “integrate dimensions into clinical practice.” The epidemiology and associated phenomenology of formal thought disorder (FTD) have been described but not reviewed. We aimed to carry out a systematic review of FTD to this end. Methods: A systematic review of FTD literature, from 1978 to 2013, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 881 abstracts were reviewed and 120 articles met inclusion criteria; articles describing FTD factor structure (n = 15), prevalence and longitudinal course (n = 41), role in diagnosis (n = 22), associated clinical variables (n = 56), and influence on outcome (n = 35) were included. Prevalence estimates for FTD in psychosis range from 5% to 91%. Dividing FTD into domains, by factor analysis, can accurately identify 91% of psychotic diagnoses. FTD is associated with increased clinical severity. Poorer outcomes are predicted by negative thought disorder, more so than the typical construct of “disorganized speech.” Conclusion: FTD is a common symptom of psychosis and may be considered a marker of illness severity. Detailed dimensional assessment of FTD can clarify diagnosis and may help predict prognosis.Key words: formal thought disorder, thought disorder, phenomenology, epidemiology, prognosis, psychosis, schizophrenia, language, communication     

Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age

Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRS_SCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = −0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRS_SCZ. Taken together, our findings indicate that cognitive biomarkers—“top-down inhibition” impairments in particular—may be of critical importance as indicators of psychosis vulnerability.     

Evaluating the tendencies of community practitioners who actively practice in child and adolescent psychiatry to diagnose and treat DSM-5 attenuated psychotic syndrome

The detection of individuals at clinical ultra-high risk for psychosis (CHR-P) may be a key limiting step for early interventions, and there is some uncertainty regarding the true clinical reliability of the CHR-P states. The aim of this study was to explore how practitioners who were in the direct treatment of children with psychiatric disorders [child psychiatry specialists/trainees (n = 227, n = 131), adult psychiatrists (n = 27), and child neurologists (n = 2)] perceive the DSM-5-Attenuated Psychosis Syndrome (DSM-5-APS), and their clinical routine practice in the treatment of it. Three vignettes describing fictional cases presented with symptoms of either DSM-5-Schizophrenia, DSM-5-APS, and no psychotic symptoms were created. We asked these practitioners to apply a DSM-5 diagnosis and to choose appropriate treatment(s) for these vignettes. Of the responders, 43% correctly diagnosed the APS vignette, whereas 37.4% mentioned that it had a full-blown psychotic episode. Regarding the therapeutic approach for the APS vignette, 72.1% of all practitioners chose a psychopharmacological intervention and 32% individual psychotherapy. This study showed that the diagnostic inter-rater reliability of the DSM-5-APS among child/adolescent mental health practitioners was consistent with the results from the DSM-5 field trials (Kappa = 0.46). Moreover, almost three in four practitioners endorsed psychopharmacological intervention as a treatment option for the DSM-5-APS case. The lack of evidence of psychopharmacological interventions in CHR-P situations emphasizes that the least harmful interventions should be recommended. Thus, our findings indicated a need for raising awareness regarding the CHR-P paradigm and its treatment as well as the development of solid guidelines that can be implemented in clinical practice.

     

Variability in suicidal ideation during treatment for individuals at clinical high risk for psychosis: The importance of repeated assessment

Aim

Suicide risk is elevated among individuals at clinical high risk for psychosis (CHR-P). The current study examined variability in suicidal ideation during treatment for individuals at CHR-P.

Methods

A retrospective chart review was used to examine the course of suicidal ideation during 16 sessions of individual psychotherapy for 25 individuals at CHR-P.

Results

Suicidal ideation was reported by 24% of participants at session 1 and 16% at session 16, with minimal within-subject change in the presence of suicidal ideation across the two time points. However, a more fine-grained investigation at each session indicated that 60% of individuals at CHR-P experienced suicidal ideation at least once during treatment. Additionally, there was great variability in suicidal ideation both within and between participants over the course of the 16 sessions.

Conclusions

These findings highlight the importance of repeated assessment when examining suicidal ideation as a treatment outcome for individuals at CHR-P.     

Comorbid Depressive and Anxiety Disorders in 509 Individuals With an At-Risk Mental State: Impact on Psychopathology and Transition to Psychosis

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients.Key words: psychosis, schizophrenia, ultra high risk, ARMS, prodromal, attenuated psychosis, psychosis risk, depression, anxiety     

Appraisals and Responses to Experimental Symptom Analogues in Clinical and Nonclinical Individuals With Psychotic Experiences

Objective: Cognitive models of psychosis suggest that anomalous experiences alone do not always lead to clinical psychosis, with appraisals and responses to experiences being central to understanding the transition to “need for care”. Methods: The appraisals and response styles of Clinical (C; n = 28) and Nonclinical (NC; n = 34) individuals with psychotic experiences were compared following experimental analogues of thought interference (Cards Task) and auditory hallucinations (Virtual Acoustic Space Paradigm). Results: The groups were matched in terms of their psychotic experiences. As predicted, the C group scored higher than the NC group on maladaptive appraisals following both tasks, rated the experience as more personally significant, and was more likely to incorporate the experimental setup into their ongoing experiences. The C group also appraised the Cards Task as more salient, distressing, and threatening; this group scored higher on maladaptive—and lower on adaptive—response styles, than the NC group on both tasks. Conclusions: The findings are consistent with cognitive models of psychosis, with maladaptive appraisals and response styles characterizing the C group only. Clinical applications of both tasks are suggested to facilitate the identification and modification of maladaptive appraisals.Key words: psychosis continuum, cognitive model of psychosis, appraisals, experimental analogues of psychotic symptoms     

Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study

Treatment and prevention studies over the past decade have enrolled patients believed to be at risk for future psychosis. These patients were considered at risk for psychosis by virtue of meeting research criteria derived from retrospective accounts of the psychosis prodrome. This study evaluated the diagnostic validity of the prospective “prodromal risk syndrome” construct. Patients assessed by the Structured Interview for Prodromal Syndromes as meeting criteria of prodromal syndromes (n = 377) from the North American Prodrome Longitudinal Study were compared with normal comparison (NC, n = 196), help-seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on variables from cross-sectional demographic, symptom, functional, comorbid diagnostic, and family history domains of assessment as well as on follow-up outcome. Prodromal risk syndrome patients as a group were robustly distinguished from NC subjects across all domains and distinguished from HSC subjects and from FHR subjects on most measures in many of these domains. Adolescent and young adult SPD patients, while distinct from prodromal patients on definitional grounds, were similar to prodromals on multiple measures, consistent with SPD in young patients possibly being an independent risk syndrome for psychosis. The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).     

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients’ fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.Key words: mental disorder, glutathione, arginine, extracellular matrix, phospholipid, metabolism     

Debate: Better use of existing services,not more new pathways,is required for psychosis prevention in young people – Commentary on Salazar de Pablo and Arango: ‘Prevention of psychosis in adolescents: does CAMHS have a role?’

Background

There has been much academic interest in ‘the clinical high-risk state for psychosis’ (CHR-P) concept. Whilst early intervention in psychosis (EIP) services have offered input to individuals meeting the CHR-P criteria the involvement of CAMHS clinicians in supporting young people with ideational and perceptual disturbance has been more inconsistent and uncertain.

Method

We bring together our relevant lived experience, empirical evidence and clinical and research expertise to write this commentary.

Results

We assert that the CHR-P paradigm needs to be revised. This should reflect the low transition rates to psychosis and the prevalent general, impairing psychopathology in individuals meeting these criteria. Nevertheless, it is clear that both CAMHS and EIP services have potential roles in meeting the needs of young people affected by distressing ideational and perceptual disturbance.

Conclusions

We suggest that new care pathways and services are not required for young people affected by distressing psychosis-like experiences. Rather more effective joint working between CAMHS, EIP, crisis services and other agencies could meet the needs of these young people more comprehensively.     

Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: “Poor,” “Middle,” “Catch-up,” and “Good” trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F_3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the “Poor” outcome cluster (β = +0.145) but decreased over time in the “Catch-up” cluster (β = −0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery.     

Psychotic Disorders and Repeat Offending: Systematic Review and Meta-analysis

Objective: To undertake a systematic review and meta-analysis on the risk of repeat offending in individuals with psychosis and to assess the effect of potential moderating characteristics on risk estimates. Methods: A systematic search was conducted in 6 bibliographic databases from January 1966 to January 2009, supplemented with correspondence with authors. Studies that reported risks of repeat offending in individuals with psychotic disorders (n = 3511) compared with individuals with other psychiatric disorders (n = 5446) and healthy individuals (n = 71 552) were included. Risks of repeat offending were calculated using fixed- and random-effects models to calculate pooled odds ratios (ORs). Subgroup and meta-regression analyses were conducted to examine how risk estimates were affected by various study characteristics including mean sample age, study location, sample size, study period, outcome measure, duration of follow-up, and diagnostic criteria. Results: Twenty-seven studies, which included 3511 individuals with psychosis, were identified. Compared with individuals without any psychiatric disorders, there was a significantly increased risk of repeat offending in individuals with psychosis (pooled OR = 1.6, 95% confidence interval [CI] = 1.4–1.8), although this was only based on 4 studies. In contrast, there was no association when individuals with other psychiatric disorders were used as the comparison group (pooled OR = 1.0, 95% CI = 0.7–1.3), although there was substantial heterogeneity. Higher risk estimates were found in female-only samples with psychosis and in studies conducted in the United States. Conclusions: The association between psychosis and repeat offending differed depending on the comparison group. Despite this, we found no support for the findings of previous reviews that psychosis is associated with a lower risk of repeat offending.     

Prevalence and Clinical Significance of DSM-5–Attenuated Psychosis Syndrome in Adolescents and Young Adults in the General Population: The Bern Epidemiological At-Risk (BEAR) Study

Objective: Section III of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists attenuated psychosis syndrome as a condition for further study. One important question is its prevalence and clinical significance in the general population. Method: Analyses involved 1229 participants (age 16–40 years) from the general population of Canton Bern, Switzerland, enrolled from June 2011 to July 2012. “Symptom,” “onset/worsening,” “frequency,” and “distress/disability” criteria of attenuated psychosis syndrome were assessed using the structured interview for psychosis-risk syndromes. Furthermore, help-seeking, psychosocial functioning, and current nonpsychotic axis I disorders were surveyed. Well-trained psychologists performed assessments using the computer-assisted telephone interviewing technique. Results: The symptom criterion was met by 12.9% of participants, onset/worsening by 1.1%, frequency by 3.8%, and distress/disability by 7.0%. Symptom, frequency, and distress/disability were met by 3.2%. Excluding trait-like attenuated psychotic symptoms (APS) decreased the prevalence to 2.6%, while adding onset/worsening reduced it to 0.3%. APS were associated with functional impairments, current mental disorders, and help-seeking although they were not a reason for help-seeking. These associations were weaker for attenuated psychosis syndrome. Conclusions: At the population level, only 0.3% met current attenuated psychosis syndrome criteria. Particularly, the onset/worsening criterion, originally included to increase the likelihood of progression to psychosis, lowered its prevalence. Because progression is not required for a self-contained syndrome, a revision of the restrictive onset criterion is proposed to avoid the exclusion of 2.3% of persons who experience and are distressed by APS from mental health care. Secondary analyses suggest that a revised syndrome would also possess higher clinical significance than the current syndrome.Key words: attenuated psychosis syndrome, general population, prevalence, distress, disability, functional impairment     

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

Background:

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes.

Methods:

Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.

Results:

The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.

Conclusions:

Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.Key words: schizophrenia, psychosis, endophenotypes, cognition, biomarkers, heritability     

Neurocognition in the Extended Psychosis Phenotype: Performance of a Community Sample of Adolescents With Psychotic Symptoms on the MATRICS Neurocognitive Battery

Neurocognitive dysfunction is well established in psychosis, but recent work suggests that processing speed deficits might represent a particularly important cognitive deficit. A number of significant confounds, however, such as disease chronicity and antipsychotic medication use, have been shown to affect processing speed, causing debate as to the core cognitive features of psychosis. We adopted a novel strategy of testing neurocognitive performance in the “extended psychosis phenotype,” involving community-based adolescents who are not clinically psychotic but who report psychotic symptoms and who are at increased risk of psychosis in adulthood. This allows investigation of the earliest cognitive factors associated with psychosis risk, while excluding potential confounds such as disease chronicity and antipsychotic use. A population sample of 212 school-going adolescents aged 11–13 years took part in this study. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Neurocognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus neurocognitive battery. Adolescents with psychotic symptoms performed significantly more poorly on 3 processing speed tasks: Trail Making Test-A (F = 3.3, P < .05), Trail Making Test-B (F = 3.1, P < .05), and digit symbol coding task (F = 7.0, P < .001)—as well as on a nonverbal working memory (spatial span) task (F = 3.2, P < .05). Our findings support the idea that neurocognitive impairment, and processing speed impairment in particular, is a core feature of psychosis risk. This group likely demonstrates some of the earliest cognitive impairments associated with psychosis vulnerability.Key words: epidemiology/adolescents/cognitionKey words: epidemiology, adolescents, cognition