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The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes-it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology.

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. Results: In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). Conclusions: The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population. [ABSTRACT FROM AUTHOR]

Facial emotion expressions play a central role in interpersonal interactions; these displays are used to predict and influence the behavior of others. Despite their importance, quantifying and analyzing the dynamics of brief facial emotion expressions remains an understudied methodological challenge. Here, we present a method that leverages machine learning and network modeling to assess the dynamics of facial expressions. Using video recordings of clinical interviews, we demonstrate the utility of this approach in a sample of 96 people diagnosed with psychotic disorders and 116 never-psychotic adults. Participants diagnosed with schizophrenia tended to move from neutral expressions to uncommon expressions (e.g., fear, surprise), whereas participants diagnosed with other psychoses (e.g., mood disorders with psychosis) moved toward expressions of sadness. This method has broad applications to the study of normal and altered expressions of emotion and can be integrated with telemedicine to improve psychiatric assessment and treatment. [ABSTRACT FROM AUTHOR]

Background: Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear. Method: We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning. Results: MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (β = 0.19), everyday functioning (β = −0.13), and illness severity (β = −0.12) at follow-up. Meanwhile, initial IQ (β = −0.24), negative symptoms (β = 0.23), and illness severity (β = −0.16) were significant predictors of worsening MMN amplitude five years later. Conclusions: These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time. [ABSTRACT FROM AUTHOR]

Introduction: Illness course plays a crucial role in delineating psychiatric disorders. However, existing nosologies consider only its most basic features (e.g., symptom sequence, duration). We developed a Dynamic Causal Model (DCM) that characterizes course patterns more fully using dense timeseries data. This foundational study introduces the new modeling approach and evaluates its validity using empirical and simulated data. Methods: A three-level DCM was constructed to model how latent dynamics produce symptoms of depression, mania, and psychosis. This model was fit to symptom scores of nine patients collected prospectively over four years, following first hospitalization. Simulated subjects based on these empirical data were used to evaluate model parameters at the subject-level. At the group-level, we tested the accuracy with which the DCM can estimate the latent course patterns using Parametric Empirical Bayes (PEB) and leave-one-out cross-validation. Results: Analyses of empirical data showed that DCM accurately captured symptom trajectories for all nine subjects. Simulation results showed that parameters could be estimated accurately (correlations between generative and estimated parameters >= 0.76). Moreover, the model could distinguish different latent course patterns, with PEB correctly assigning simulated patients for eight of nine course patterns. When testing any pair of two specific course patterns using leave-one-out cross-validation, 30 out of 36 pairs showed a moderate or high out-of-samples correlation between the true groupmembership and the estimated group-membership values. Conclusion: DCM has been widely used in neuroscience to infer latent neuronal processes from neuroimaging data. Our findings highlight the potential of adopting this methodology for modeling symptom trajectories to explicate nosologic entities, temporal patterns that define them, and facilitate personalized treatment. [ABSTRACT FROM AUTHOR]

Background: Life events (LEs) are a risk factor for first onset and relapse of psychotic disorders. However, the impact of LEs on specific symptoms – namely reality distortion, disorganization, negative symptoms, depression, and mania – remains unclear. Moreover, the differential effects of negative v. positive LEs are poorly understood. Methods: The present study utilizes an epidemiologic cohort of patients (N = 428) ascertained at first-admission for psychosis and followed for a decade thereafter. Symptoms were assessed at 6-, 24-, 48-, and 120-month follow-ups. Results: We examined symptom change within-person and found that negative events in the previous 6 months predicted an increase in reality distortion (β = 0.07), disorganized (β = 0.07), manic (β = 0.08), and depressive symptoms (β = 0.06), and a decrease in negative symptoms (β = −0.08). Conversely, positive LEs predicted fewer reality distortion (β = −0.04), disorganized (β = −0.04), and negative (β = −0.13) symptoms, and were unrelated to mood symptoms. A between-person approach to the same hypotheses confirmed that negative LEs predicted change in all symptoms, while positive LEs predicted change only in negative symptoms. In contrast, symptoms rarely predicted future LEs. Conclusions: These findings confirm that LEs have an effect on symptoms, and thus contribute to the burden of psychotic disorders. That LEs increase positive symptoms and decrease negative symptoms suggest at least two different mechanisms underlying the relationship between LEs and symptoms. Our findings underscore the need for increased symptom monitoring following negative LEs, as symptoms may worsen during that time. [ABSTRACT FROM AUTHOR]

Importance: Schizophrenia is associated with major cognitive deficits and has been conceptualized as both a neurodevelopmental and a neurodegenerative disorder. However, when deficits develop and how they change over the course of illness is uncertain.Objective: To trace cognition from elementary school to old age to test neurodevelopmental and neurodegenerative theories of psychotic disorders.Design, Setting, and Participants: Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were recruited from all 12 inpatient psychiatric facilities in Suffolk County, New York. This analysis concerns the 428 participants with at least 2 estimates of general cognitive ability. Data were collected between September 1989 and October 2019, and data were analyzed from January 2020 to October 2021.Exposures: Psychiatric hospitalization for psychosis.Main Outcomes and Measures: Preadmission cognitive scores were extracted from school and medical records. Postonset cognitive scores were based on neuropsychological testing at 6-month, 24-month, 20-year, and 25-year follow-ups.Results: Of the 428 included individuals (212 with schizophrenia and 216 with other psychotic disorders), 254 (59.6%) were male, and the mean (SD) age at psychosis onset was 27 (9) years. Three phases of cognitive change were observed: normative, declining, and deteriorating. In the first phase, cognition was stable. Fourteen years before psychosis onset, those with schizophrenia began to experience cognitive decline at a rate of 0.35 intelligence quotient (IQ) points per year (95% CI, 0.29-0.42; P < .001), a significantly faster decline than those with other psychotic disorders (0.15 IQ points per year; 95% CI, 0.08-0.22, P < .001). At 22 years after onset, both groups declined at a rate of 0.59 IQ points per year (95% CI, 0.25-0.94; P < .001).Conclusions and Relevance: In this cohort study, cognitive trajectories in schizophrenia were consistent with both a neurodevelopmental and neurodegenerative pattern, resulting in a loss of 16 IQ points over the period of observation. Cognitive decline began long prior to psychosis onset, suggesting the window for primary prevention is earlier than previously thought. A window for secondary prevention emerges in the third decade of illness, when cognitive declines accelerate in individuals with schizophrenia and other psychotic disorders. [ABSTRACT FROM AUTHOR]

The concept of schizophrenia, operationalized in diagnostic manuals, faces existential challenges of low reliability, arbitrary boundaries, overlap with other disorders, and heterogeneity. The Hierarchical Taxonomy Of Psychopathology (HiTOP) was developed to address these challenges. It conceptualizes psychotic disorders as continuous with normality. To alleviate heterogeneity, psychotic disorders are decomposed into 14 tightly-knit symptom and trait dimensions. These narrow dimensions form two broader spectra-psychoticism (e.g., positive symptoms, peculiarity, fantasy-proneness) and detachment (e.g., negative symptoms, emotional detachment, romantic disinterest)-that comprise the psychosis superspectrum. The full HiTOP model includes four other spectra that can be useful in a comprehensive evaluation. This model is undergoing rigorous validation. It has shown greater reliability, explanatory power, and prognostic value than schizophrenia diagnosis. The HiTOP approach produced promising evidence of clinical utility in surveys of clinicians. The HiTOP reconceptualization of schizophrenia suggests four major implications. First, schizophrenia spans two spectra, and therefore detachment is important to study including in people who have never been psychotic. Second, large population-based studies with comprehensive profiling of psychopathology can address shortcomings of case-control design. Third, elevations on psychoticism and detachment dimensions early in life offer opportunities for prevention. Fourth, actionable ranges can be identified on dimensions to guide specific clinical decisions. The elaborate HiTOP model may be unnecessary in acute treatment settings, but it can benefit prevention, long-term management, and research. The categorical schizophrenia concept offers valuable continuity and can be used in parallel with HiTOP, but we predict that eventually the dimensional approach will make this category obsolete. [ABSTRACT FROM AUTHOR]

The Hierarchical Taxonomy of Psychopathology consortium aims to develop a comprehensive self-report measure to assess psychopathology dimensionally. The current research describes the initial conceptualization, development, and item selection for the thought disorder spectrum and related constructs from other spectra. The thought disorder spectrum is defined primarily by the positive and disorganized traits and symptoms of schizophrenia-spectrum disorders. The Thought Disorder Sub-Workgroup identified and defined 16 relevant constructs and wrote 10 to 15 items per each construct. These items were administered, along with detachment and mania items, to undergraduates and people with serious mental illness. Three hundred and sixty-five items across 25 scales were administered. An exploratory factor analysis of the scale scores suggested a two-factor structure corresponding to positive and negative symptoms for two samples. The mania scales loaded with the positive factor, while the detachment scales loaded with the negative factor. Item-level analyses resulted in 19 preliminary scales, including 215 items that cover the range of thought disorder pathology, and will be carried forward for the next phase of data collection/analysis. [ABSTRACT FROM AUTHOR]

Background: Performance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning. Methods: Data were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways. Results: Blunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26–0.35), negative symptom severity (r = 0.17–0.25), and poor real-world functioning (r = 0.17–0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β = 0.10). Conclusions: This supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders. [ABSTRACT FROM AUTHOR]

Emotional face perception (EFP) deficits have been identified as a significant feature of psychotic disorders and are associated with symptoms and real-world functioning in these disorders. The amygdala is frequently implicated in EFP and bears extensive structural connectivity with other brain regions supporting EFP. Amygdala functional connectivity during attentional control of implicitly processed emotional faces in psychotic disorders is well examined. However, it is unclear whether amygdala functional connectivity while explicitly processing emotional faces contributes to EFP deficits in psychotic disorders. Further, it is unclear whether these connectivity differences are associated with symptoms or functioning and if these relationships are transdiagnostic across psychotic disorders. We used functional magnetic resonance imaging (fMRI) and seed-based functional connectivity analyses to examine connectivity of amygdala to other regions of the face processing network during an EFP task. The sample consisted of 55 cases with psychotic disorders and 29 participants with no history of psychosis (NP). Results indicated that, compared to NP, cases showed worse accuracy, greater inferior frontal gyrus (IFG) activation, and greater amygdala-insula connectivity while matching emotional and neutral faces. Additionally, worse accuracy, greater IFG activation, greater amygdala-insula and amygdala-IFG connectivity during emotional vs. neutral faces was associated with worse negative symptoms and greater deficits in social and global functioning in cases. Importantly, these relationships transcended diagnostic categories, and applied across psychotic disorders. The present study presents compelling evidence relating alterations in amygdala functional connectivity during explicit EFP with clinical and functioning deficits seen across psychotic disorders. [ABSTRACT FROM AUTHOR]

Background: Psychosis is a risk factor for aging-related conditions and early mortality. Little is known about the age-specific risk of objectively measured physical functional limitations among individuals with serious mental illness.Methods: The Suffolk County Mental Health Project is a prospective study of individuals hospitalized for the first time for psychosis. To assess physical functioning at midlife and to identify emerging risk factors for older-age changes, 101 participants with schizophrenia (mean age = 47.2, SD = 8.0 years; 41.6% female) and 112 participants with other psychoses (mean age = 48.2, SD = 9.5 years; 45.5% female) were assessed for chair-rise and balance limitations 20 years after diagnosis. A never-psychotic comparison group of 237 age/sex/geographically matched community controls was similarly assessed (mean age = 50.3, SD = 8.8 years; 44.7% female). Logistic regression was used to examine group differences in prevalence of poor performance and demographic, medical, and treatment correlates.Results: Chair-rise limitations (45.5% [35.8-55.3]) and balance limitations (17.2% [9.8-24.5]) were common in individuals with schizophrenia. Prevalence of chair-rise limitations was higher in schizophrenia (46.3%) than in other psychotic disorders (31.9%) and never-psychotic group (22.1%), whereas risk of balance limitations was higher in schizophrenia (17.2%) compared with never-psychotic controls (8.1%). Schizophrenia was a significant risk factor for chair-rise (adjusted odds ratio = 3.01 [1.79-5.08], p < .001) and balance limitations (adjusted odds ratio = 2.63, [1.25-5.51], p = .010). Multivariable analysis of symptom severity found avolition was associated with chair-rise limitations, but not balance, independent of diagnosis.Conclusion: Physical limitations are crucial because they identify existing problems with mobility and portend an increased risk of disability and death. Because participants with schizophrenia were at increased risk of physical limitations, assessments of chair-rise and balance limitations may be critical to monitoring individuals with psychosis. [ABSTRACT FROM AUTHOR]

Importance: It remains uncertain whether people with psychotic disorders experience progressive cognitive decline or normal cognitive aging after first hospitalization. This information is essential for prognostication in clinical settings, deployment of cognitive remediation, and public health policy.Objective: To examine long-term cognitive changes in individuals with psychotic disorders and to compare age-related differences in cognitive performance between people with psychotic disorders and matched control individuals (ie, individuals who had never had psychotic disorders).Design, Setting, and Participants: The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Cognitive functioning was assessed 2 and 20 years later. Patients were recruited from the 12 inpatient facilities of Suffolk County, New York. At year 20, the control group was recruited by random digit dialing and matched to the clinical cohort on zip code and demographics. Data were collected between September 1991 and July 2015. Analysis began January 2016.Main Outcomes and Measures: Change in cognitive functioning in 6 domains: verbal knowledge (Wechsler Adult Intelligence Scale-Revised vocabulary test), verbal declarative memory (Verbal Paired Associates test I and II), visual declarative memory (Visual Reproduction test I and II), attention and processing speed (Symbol Digit Modalities Test-written and oral; Trail Making Test [TMT]-A), abstraction-executive function (Trenerry Stroop Color Word Test; TMT-B), and verbal fluency (Controlled Oral Word Association Test).Results: A total of 705 participants were included in the analyses (mean [SD] age at year 20, 49.4 [10.1] years): 445 individuals (63.1%) had psychotic disorders (211 with schizophrenia spectrum [138 (65%) male]; 164 with affective psychoses [76 (46%) male]; 70 with other psychoses [43 (61%) male]); and 260 individuals (36.9%) in the control group (50.5 [9.0] years; 134 [51.5%] male). Cognition in individuals with a psychotic disorder declined on all but 2 tests (average decline: d = 0.31; range, 0.17-0.54; all P < .001). Cognitive declines were associated with worsening vocational functioning (Visual Reproduction test II: r = 0.20; Symbol Digit Modalities Test-written: r = 0.25; Stroop: r = 0.24; P < .009) and worsening negative symptoms (avolition: Symbol Digit Modalities Test-written: r = -0.24; TMT-A: r = -0.21; Stroop: r = -0.21; all P < .009; inexpressivity: Stroop: r = -0.22; P < .009). Compared with control individuals, people with psychotic disrders showed age-dependent deficits in verbal knowledge, fluency, and abstraction-executive function (vocabulary: β = -0.32; Controlled Oral Word Association Test: β = -0.32; TMT-B: β = 0.23; all P < .05), with the largest gap among participants 50 years or older.Conclusions and Relevance: In individuals with psychotic disorders, most cognitive functions declined over 2 decades after first hospitalization. Observed declines were clinically significant. Some declines were larger than expected due to normal aging, suggesting that cognitive aging in some domains may be accelerated in this population. If confirmed, these findings would highlight cognition as an important target for research and treatment during later phases of psychotic illness. [ABSTRACT FROM AUTHOR]

Background: Since the Iowa 500 study, residential and occupational status have been frequently used as indicators of everyday achievements in research on schizophrenia and bipolar disorder. The relationships of residential and occupational status with impairment in multiple domains including physical health indicators across these two diagnoses, however, have rarely been studied. We examined these relationships at the 20-year follow-up assessment of a first-admission sample.Methods: We included 146 participants with schizophrenia and 87 with bipolar disorder with psychosis who participated in the 20-year follow-up of the Suffolk County Mental Health Project. In addition to interviewer-based ratings of employment and residential independence, we examined self-reported impairment derived from the WHODAS, standard measures of current psychopathology, indicators of obesity, as well as performance-based measures of physical and cognitive functioning.Results: Participants with bipolar disorder were more likely to live independently and be gainfully employed; they also performed significantly better on each indicator of impairment apart from balance ability. In both groups, unemployment, but not residential independence, was associated with greater self-reported disability on the WHODAS. Residential independence, gainful employment, and subjective disability were also associated with better physical functioning. Across the two groups, psychiatric symptoms and physical functioning were the major determinants of subjective disability.Discussion: People with psychotic bipolar disorder were more likely to be gainfully employed and living independently than participants with schizophrenia but as a group, much less frequently than population standards. Interventions aimed at physical fitness may have the potential to improve both objective functioning and perceived disability. [ABSTRACT FROM AUTHOR]

Objective: Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization.Method: The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). Participants were assessed in person six times over two decades; 373 completed the 20-year follow-up (68% of survivors); 175 had schizophrenia/schizoaffective disorder. Global Assessment of Functioning (GAF), psychotic symptoms, and mood symptoms were rated at each assessment. Month 6, when nearly all participants were discharged from the index hospitalization, was used as a reference.Results: In the schizophrenia group, mean GAF scores declined from 49 at month 6 to 36 at year 20. Negative and positive symptoms also worsened (Cohen's d values, 0.45-0.73). Among participants without schizophrenia, GAF scores were higher initially (a mean of approximately 64) but declined by 9 points over the follow-up period. Worsening began between years 5 and 8. Neither aging nor changes in antipsychotic treatment accounted for the declines. In all disorders, depression improved and manic symptoms remained low across the 20 years.Conclusions: The authors found substantial symptom burden across disorders that increased with time and ultimately may undo initial treatment gains. Previous studies have suggested that better health care delivery models may preempt this decline. In the United States, these care needs are often not met, and addressing them is an urgent priority. [ABSTRACT FROM AUTHOR]

Objective: Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically.Methods: Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined.Results: Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories.Conclusions: The results highlight substantial variability of social outcomes within diagnoses-albeit overall worse social outcomes in schizophrenia spectrum disorders-and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses. [ABSTRACT FROM AUTHOR]

Objective There is an increased prevalence of obesity in schizophrenia and bipolar disorder, leading to a disproportionate risk of adverse health conditions. Prospective, long-term weight gain data, however, are scarce. Methods We analyzed data from the Suffolk County Mental Health Project cohort of consecutive first admissions with psychosis recruited from September 1989 to December 1995 and subsequently followed for 20 years, focusing on people with schizophrenia (n=146) and bipolar disorder (n=87). The time course of weight gain was examined using a 2 (group)×5 (time) mixed-model repeated measures ANOVA, and body mass index ( BMI) scores at the first (6 months) and second (2 years) assessments were compared to examine whether early overweight predicted later obesity. Results There was a statistically significant effect of time ( F(1,210)=68.06, P<.001) and diagnosis ( F(1,210)=29.18, P<.001) on BMI, but not the interaction of time×diagnosis ( F(1,210)=0.88, P=.48). Most participants had normal BMIs at the first two assessments. Early overweight was a predictor of eventual obesity for both groups. At the 20-year follow-ups, approximately 50% of the bipolar and 62% of the schizophrenia sample were obese, with a greater prevalence of obesity in schizophrenia at each assessment (all P<.02), except for years 4 ( P=.12) and 20 ( P=.27). Conclusions Nearly two-thirds of the participants with schizophrenia and over half of those with bipolar disorder were obese 20 years after first hospitalization for psychosis, considerably higher than the rate for adults in New York State (27%). Early intervention may be required to prevent long-term consequences of obesity-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

There is considerable variation in negative and positive symptoms of psychosis, global functioning, and emotional face perception (EFP), not only in schizophrenia but also in other psychotic disorders and healthy individuals. However, EFP impairment and its association with worse symptoms and global functioning have been examined largely in the domain of schizophrenia. The present study adopted a dimensional approach to examine the association of behavioral and neural measures of EFP with symptoms of psychosis and global functioning across individuals with schizophrenia spectrum (SZ; N = 28) and other psychotic (OP; N = 29) disorders, and never-psychotic participants (NP; N = 21). Behavioral and functional MRI data were recorded as participants matched emotional expressions of faces and geometrical shapes. Lower accuracy and increased activity in early visual regions, hippocampus, and amygdala during emotion versus shape matching were associated with higher negative, but not positive, symptoms and lower global functioning, across all participants. This association remained even after controlling for group-related (SZ, OP, and NP) variance, dysphoria, and antipsychotic medication status, except in amygdala. Furthermore, negative symptoms mediated the relationship between behavioral and brain EFP measures and global functioning. This study provides some of the first evidence supporting the specific relationship of EFP measures with negative symptoms and global functioning across psychotic and never-psychotic samples, and transdiagnostically across different psychotic disorders. Present findings help bridge the gap between basic EFP-related neuroscience research and clinical research in psychosis, and highlight EFP as a potential symptom-specific marker that tracks global functioning. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

This Viewpoint discusses 2 testable hypotheses for prevention of dementia and premature mortality after cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the association of perceptions of traumatic experiences during psychiatric hospitalizations and treatment participation. Methods: Participants (N=395) in the Suffolk County Mental Health Project, who had been admitted for the first time for a psychotic disorder ten years earlier, were interviewed. The authors examined associations of perceived trauma and distressing or coercive experiences during hospitalizations in the past ten years with patient characteristics and treatment participation. Results: Sixty-nine percent of participants reported perceived trauma. Perceived trauma was more common among females versas males and homemakers versus full-time workers. It was not associated with treatment seeking or time in treatment. However, reporting forced medication was associated with reduced time in treatment, especially for persons with schizophrenia spectrum disorders. Conclusions: Although perceptions of trauma during psychiatric hospitalization were common, they may be unrelated to treatment participation. However, there was modest evidence of a link between coercive experiences and reduced treatment time. [ABSTRACT FROM AUTHOR]

IMPORTANCE Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis. OBJECTIVE To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome. DESIGN. SETTING, AND PARTICIPANTS The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413. MAIN OUTCOMES AND MEASURES Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists. RESULTS We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity--10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF--consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome. CONCLUSIONS AND RELEVANCE Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy. [ABSTRACT FROM AUTHOR]

Psychotic disorders are characterized by profoundly blunted neural responses to errors, as indicated by reductions in two event-related potential (ERP) components: the error-related negativity (ERN) and error positivity (Pe). The potential utility of the ERN and Pe as biomarkers for psychotic disorders is currently limited, however, by an incomplete understanding of their psychometric properties. To address this gap in the literature, we considered the reliability and validity of these measures in both healthy individuals (n = 52) and patients with psychotic illness (n = 84) across two experimental paradigms that have been used in previous studies in schizophrenia: a flankers task and a picture/word matching task. Internal consistency reliability was higher on the flankers compared to the picture/word task overall. On the flankers task, fair internal consistency was achieved among patients with relatively few trials (ERN = five trials. Pe = 12 trials). The number of available error trials influenced reliability among patients more than among healthy individuals, and on the picture/word task more than the flankers task. Moderate convergent validity for the ERN and Pe was observed across tasks in both the patient and healthy groups. ERPs on the flankers task exhibited external validity, and were related to several clinical characteristics, including diagnosis, negative symptom severity, rehospitalization, employment, and neuroticism; asso-ciations with the picture/word task were generally weaker. These data indicate that task differences can strongly affect psychometric properties of error-related neural activity indices in healthy and patient populations. [ABSTRACT FROM AUTHOR]

Background: Studies of event-related potentials have consistently shown that schizophrenia is associated with a blunted error-related negativity (ERN), indicating a deficit in error monitoring. It is unknown whether this deficit is unique to schizophrenia or is common to psychotic disorders more broadly, and its associations with clinical characteristics of the illness are not well understood. Methods: The ERN and the error positivity (Pe) were recorded from 33 individuals with schizophrenia, 45 individuals with other psychotic disorders, and 33 healthy control subjects. Patients were drawn from a cohort with psychotic disorders followed since first hospitalization and diagnosed by consensus based on 10 years of observation. Results: The ERN was profoundly blunted in the patient group, regardless of diagnosis, indicating that this deficit is not unique to schizophrenia. The Pe, meanwhile, was blunted only among individuals with schizophrenia, indicating that the ERN and Pe are differentially related to psychotic illnesses. A blunted ERN was associated with more severe negative symptoms and poorer real-world functioning, as indicated by unemployment and re-hospitalization over 10 years of illness. Although reduced compared with control subjects, ERN amplitude was greater in patients with higher neuroticism, indicating that error processing is moderated by personality differences in the same manner as in healthy populations. Conclusions: The current study advances the literature by evaluating diagnostic specificity and functional correlates of impaired error processing in psychosis. [Copyright &y& Elsevier]

Little is known about the longitudinal relationship of hopelessness to attempted suicide in psychotic disorders. This study addresses this gap by assessing hopelessness and attempted suicide at multiple time-points over 10 years in a first-admission cohort with psychosis ( n = 414). Approximately one in five participants attempted suicide during the 10-year follow-up, and those who attempted suicide scored significantly higher at baseline on the Beck Hopelessness Scale. In general, a given assessment of hopelessness (i.e., baseline, 6, 24, and 48 months) reliably predicted attempted suicide up to 4 to 6 years later, but not beyond. Structural equation modeling indicated that hopelessness prospectively predicted attempted suicide even when controlling for previous attempts. Notably, a cut-point of 3 or greater on the Beck Hopelessness Scale yielded sensitivity and specificity values similar to those found in nonpsychotic populations using a cut-point of 9. Results suggest that hopelessness in individuals with psychotic disorders confers information about suicide risk above and beyond history of attempted suicide. Moreover, in comparison with nonpsychotic populations, even relatively modest levels of hopelessness appear to confer risk for suicide in psychotic disorders. [ABSTRACT FROM AUTHOR]

Carlson GA, Kotov R, Chang S-W, Ruggero C, Bromet EJ. Early determinants of four-year clinical outcomes in bipolar disorder with psychosis. Bipolar Disord 2012: 14: 19-30. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar disorder with psychosis is common in inpatient settings and is associated with diverse outcomes after hospital discharge, which can range from a return to premorbid functioning with no recurrence, to a chronic or recurring illness. Less is known, however, about factors that can predict a better or worse clinical outcome. The present study sought to assess four-year clinical outcomes and their predictors in patients hospitalized for bipolar I disorder with psychosis. Methods: Participants from the Suffolk County Mental Health Project (SCMHP) with a baseline diagnosis of bipolar I disorder with psychotic features (N = 126) were reassessed using face-to-face interviews at six months, two years, and four years following their first hospitalization. At each time point, clinical status, role functioning, and treatment were assessed by highly trained interviewers using standardized instruments. Results: The majority of participants (73.2%) returned to their premorbid level of role functioning by the four-year follow-up and the median percentage of time ill during the interval was less than 20%. Nevertheless, almost half of the sample (46.9%) was rehospitalized at least once. Psychotic symptoms at baseline (particularly Schneiderian symptoms), depressive phenomenology, childhood psychopathology, and younger age at first hospitalization predicted worse outcome, whereas mood-incongruent psychotic features and age of mood disorder onset did not. Conclusions: The four-year outcomes of a first-admission cohort with bipolar I disorder with psychosis were generally favorable. Poorer premorbid functioning, Schneiderian delusions, greater depressive symptoms, and a younger age of first hospitalization portend a worse course. [ABSTRACT FROM AUTHOR]

Objective : Diagnostic shifts have been prospectively examined in the short term, but the long-term stability of diagnoses has rarely been evaluated. The authors examined diagnostic shifts over a 10-year follow-up period. Method : A cohort of 470 first-admission patients with psychotic disorders was systematically assessed at baseline and at 6-month, 2-year, and 10-year follow-ups. Longitudinal best-estimate consensus diagnoses were formulated after each assessment. Results : At baseline, the diagnostic distribution was 29.6% schizophrenia spectrum disorders, 21.1% bipolar disorder with psychotic features, 17.0% major depression with psychotic features, 2.4% substance- induced psychosis, and 27.9% other psychoses. At year 10, the distribution changed to 49.8%, 24.0%, 11.1%, 7.0%, and 8.1%, respectively. Overall, diagnoses were changed for 50.7% of study participants at some point during the study. Most participants who were initially diagnosed with schizophrenia or bipolar disorder retained the diagnosis at year 10 (89.2% and 77.8%, respectively). However, 32.0% of participants (N=98) originally given a non-schizophrenia diagnosis had gradually shifted to a schizophrenia diagnosis by year 10. The second largest shift was to bipolar disorder (10.7% of those not given this diagnosis at baseline). Changes in the clinical picture explained many diagnostic shifts. In particular, poorer functioning and greater negative and psychotic symptom ratings predicted a subsequent shift to schizophrenia. Better functioning and lower negative and depressive symptom ratings predicted the shift to bipolar disorder. Conclusions: First-admission patients with psychotic disorders run the risk of being misclassified at early stages in the illness course, including more than 2 years after first hospitalization. Diagnosis should be reassessed at all follow-up points. [ABSTRACT FROM AUTHOR]

The article discusses a study which aimed to determine how consistent is the diagnosis of major depressive disorder (MDD) with psychosis. The study involved 146 patients from psychiatric inpatient facilities of Suffolk County, New York. A total of 8.9% of participants with psychotic depression shifted from MDD to bipolar disorder, 16.4% shifted to schizophrenia and 37% showed other patterns of diagnostic change within 10 years. The use of a single assessment in the diagnosis of MDD is tackled.

Abstract: A 44 base pair insertion (“l”)/deletion (“s”) polymorphism (called 5-HTTLPR) in the 5′ promoter region of the human serotonin transporter gene (SLC6A4) modulates expression and has been associated to anxiety and depressive traits in otherwise healthy individuals. In individuals with psychiatric diagnoses, including schizophrenia, it seems to modulate symptom severity. Thus, it may be a disease modifying gene. In this study, 92 patients with psychosis (including schizophrenia, schizoaffective disorder, bipolar psychosis, and major depression) were assessed at their first hospital admission. Symptom ratings, including SANS negative symptoms, SAPS positive symptoms, and SCID depressive symptoms, were obtained. Stress was also assessed. Bi-allelic genotyping at the 5-HTTLPR locus was done. Using multiple regression models, we found that 5-HTTLPR genotype (especially in dominant models) accounted for a significant portion of the variance in SCID Depression and SANS (about 5%). In particular we found that the l allele was associated with greater psychopathology. This is consistent with our review of the literature and is at variance with findings in healthy controls that the s allele is associated with greater anxiety and depression levels. We believe that this set of findings argues for principled reversal of directionality in associations at the 5-HTTLPR locus and raises the possibility that allelic variation may have very different consequences for personality traits or psychiatric symptoms depending on epistasis or epigenetic context. Furthermore, these results also imply that categorical diagnostic distinctions may still be relevant in understanding some genetic effects. [Copyright &y& Elsevier]

Emotional deficits in psychosis are prevalent and difficult to treat. In particular, much remains unknown about facial expression abnormalities, and a key reason is that expressions are very labor-intensive to code. Automatic facial coding (AFC) can remove this barrier. The current study sought to both provide evidence for the utility of AFC in psychosis for research purposes and to provide evidence that AFC are valid measures of clinical constructs. Changes of facial expressions and head position of participants—39 with schizophrenia/schizoaffective disorder (SZ), 46 with other psychotic disorders (OP), and 108 never psychotic individuals (NP)—were assessed via FaceReader, a commercially available automated facial expression analysis software, using video recorded during a clinical interview. We first examined the behavioral measures of the psychotic disorder groups and tested if they can discriminate between the groups. Next, we evaluated links of behavioral measures with clinical symptoms, controlling for group membership. We found the SZ group was characterized by significantly less variation in neutral expressions, happy expressions, arousal, and head movements compared to NP. These measures discriminated SZ from NP well (AUC = 0.79, sensitivity = 0.79, specificity = 0.67) but discriminated SZ from OP less well (AUC = 0.66, sensitivity = 0.77, specificity = 0.46). We also found significant correlations between clinician-rated symptoms and most behavioral measures (particularly happy expressions, arousal, and head movements). Taken together, these results suggest that AFC can provide useful behavioral measures of psychosis, which could improve research on non-verbal expressions in psychosis and, ultimately, enhance treatment. • We tested the utility of automatic facial coding (AFC) in psychosis. • The SZ group was characterized by significantly less variation in some measures. • Measures discriminated SZ from the never-psychotic group well. • There were associations between clinician-rated symptoms and most measures in SZ. • These results suggest that AFC can provide useful behavioral measures of psychosis. [ABSTRACT FROM AUTHOR]

A response by Dr. Camilo J. Ruggero and colleagues to a letter to the editor about their article "Diagnostic Consistency of Major Depression With Psychosis Across 10 Years," in the September 2011 issue is presented.

Deficits in working memory (WM) and emotion processing are prominent impairments in psychotic disorders, and have been linked to reduced quality of life and real-world functioning. Translation of knowledge regarding the neural circuitry implementing these deficits into improved diagnosis and targeted treatments has been slow, possibly because of categorical definitions of disorders. Using the dimensional Research Domain Criteria (RDoC) framework, we investigated the clinical and practical utility of transdiagnostic behavioral and neural measures of emotion-related WM disruption across psychotic disorders. Behavioral and functional MRI data were recorded while 53 participants with psychotic disorders and 29 participants with no history of psychosis performed a modified n-back task with fear and neutral distractors. Hierarchical regression analyses showed that psychotic symptoms entered after diagnosis accounted for unique variance in fear versus neutral accuracy and activation in the ventrolateral, dorsolateral, and dorsomedial prefrontal cortex, but diagnostic group entered after psychotic symptoms did not. These results remained even after controlling for negative symptoms, disorganized symptoms, and dysphoria. Finally, worse accuracy and greater prefrontal activity were associated with poorer social functioning and unemployment across diagnostic groups. Present results support the transdiagnostic nature of behavioral and neuroimaging measures of emotion-related WM disruption as they relate to psychotic symptoms, irrespective of diagnosis. They also provide support for the practical utility of these markers in explaining real-world functioning. Overall, these results elucidate key aspects of the RDoC construct of WM maintenance by clarifying its transdiagnostic importance and clinical utility in psychotic disorders. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

Negative symptoms are among the greatest sources of functional impairment for individuals with schizophrenia, yet their mechanisms remain poorly understood. Olfactory impairment is associated with negative symptoms. The processing of pleasant olfactory stimuli is subserved by reward-related neural circuitry while unpleasant olfactory processing is subserved by emotion-related neural circuitry, suggesting that these two odor dimensions may offer a window into differential mechanisms of negative symptoms. We examined whether pleasant and unpleasant odor identification bears differential relationships with avolition and inexpressivity dimensions of negative symptoms, whether these relationships are transdiagnostic, and whether pleasant and unpleasant odor processing also relate differently to other domains of functioning in a sample of individuals diagnosed with schizophrenia (N = 54), other psychotic disorders (N = 65), and never-psychotic adults (N = 160). Hierarchical regressions showed that pleasant odor identification was uniquely associated with avolition, while unpleasant odor identification was uniquely associated with inexpressivity. These relationships were largely transdiagnostic across groups. Additionally, pleasant and unpleasant odor identification displayed signs of specificity with other functional and cognitive measures. These results align with past work suggesting dissociable pathomechanisms of negative symptoms and provide a potential avenue for future work using valence-specific olfactory dysfunction as a semi-objective and low-cost marker for understanding and predicting the severity of specific negative symptom profiles. [ABSTRACT FROM AUTHOR]

Background Cognitive impairments and delusions are hallmarks of schizophrenia, and are thought to be due in part to abnormalities in semantic priming. The N400, a neural measure of semantic processing, is found to be reduced in schizophrenia. However, it is unclear if individuals with other psychoses (e.g., mood disorders or substance abuse with psychotic features) also show this impairment, and whether N400 reduction relates to real-world functioning and recovery. Methods Eighty-nine individuals from the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis, and 35 healthy adults were assessed using matched, related, and unrelated picture–word pairs to elicit the N400. Patients' real-world functioning, symptomatology, and recovery were tracked since first hospitalization; EEG assessment was completed during year 15 of the study. Results Participants with schizophrenia had slower reaction times and reduced N400 to semantically incongruent stimuli relative to healthy participants. Schizophrenia and other psychoses did not differ on N400, suggesting that N400 abnormalities characterize psychosis broadly. When grouped by recovery status, patients who remained ill had a significantly blunted N400, while those who recovered did not differ from healthy adults. Few patients with schizophrenia achieved recovery; therefore recovery results are limited to the other psychosis group. Furthermore, reduced N400 and increased reaction times correlated with greater psychotic symptoms, worse global assessment of functioning scores, unemployment, and impaired social functioning. Conclusions Abnormalities in the N400 are not specific to schizophrenia; in addition, the N400 may be a useful neural correlate of recovery and real-world functioning across psychotic disorders. [ABSTRACT FROM AUTHOR]

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se. [ABSTRACT FROM AUTHOR]

Mismatch negativity (MMN) amplitude has been widely shown to be diminished in schizophrenia and, more recently, in other psychotic disorders. Although there is considerable evidence linking MMN reduction to cognitive and functional deficits in schizophrenia, there is little evidence of associations with specific psychotic symptoms. Further, it is unclear if MMN reductions relate to specific symptoms, cognitive, and functional deficits transdiagnostically across different psychotic disorders. The present study examines MMN amplitude in a large cohort of cases diagnosed with psychotic disorders including schizophrenia and schizoaffective disorder (N = 116); bipolar disorder and major depressive disorder (N = 75); and other psychotic disorders (N = 25), as well as individuals with no psychotic disorder diagnoses (N = 248). Furthermore, we examined the association of MMN with symptoms, cognitive functioning, and real-world functioning to determine whether these relationships differ by diagnosis. Results showed that MMN amplitude was reduced in cases overall compared to never-psychotic individuals, with no differences between psychotic disorders. Furthermore, there were transdiagnostic associations of reduced duration MMN (MMN-D) with worse auditory hallucinations (r = .14) and disorganization (r = .14), frequency MMN (MMN-F) with real-word functioning (r = .20) and episodic memory (r = -.22), and both components with executive functioning (MMN-D: r = -.17; MMN-F: r = -.15). Our findings relating MMN reductions with cognitive and real-world functioning replicate earlier research in schizophrenia and extend these relationships to other psychotic disorders. Furthermore, our correlations with MMN-D are consistent with computational modeling research and theoretical proposals that view MMN reduction, cognitive dysfunction, and psychotic symptoms as reflecting underlying predictive coding deficits. However, differences in relationships with MMN-F suggest that additional work is warranted on this topic. (PsycInfo Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Introduction Schizophrenia (SCZ) and bipolar disorder (BP) are linked to multiple impairments in everyday functioning which share cognitive and symptom risk factors. Other risk factors for critical aspects of every day functioning (e.g., gainful employment; residential independence) such as physical health have not been evaluated, despite poor health in SCZ and BP. Methods We analyzed 20-year follow-up data from the Suffolk County Mental Health Project cohort of consecutive first admissions with a psychotic disorder to 12 psychiatric facilities in Suffolk County, NY, between September 1989 and December 1995. Both 20-year symptom, health, and cognition data, and the 20-year course of weight gain were included as predictors of employment and residence status. Results The analysis sample consisted of 122 participants with SCZ ad BP, with SCZ participants less likely to work or live independently. Correlational analyses showed symptoms and cognition predicted vocational outcomes in both samples. The effect of diagnosis was significant for both gainful employment and independence in residence. After consideration of diagnosis, mobility and negative symptoms predicted gainful employment in both samples, but there were no additional predictors of residential independence. Prospective analysis of BMI found that baseline BMI, but not changes during the 20-year follow up, predicted labor force participation. Discussion Health status limitations were associated with residential and, particularly, employment status independent from other, previously established predictors of everyday outcomes, including cognition and symptoms. The importance of health status limitations for predicting outcome was confirmed in both SCZ and BP, with schizophrenia representing the more impaired group. [ABSTRACT FROM AUTHOR]

Error processing is impaired in psychosis, and numerous event-related potential studies have found reductions in the error-related negativity (ERN) and, more recently, the error positivity (Pe). The stability of reduced ERN/Pe in psychosis, however, is unknown. In a previous cross-sectional report, reduced ERN was associated with negative symptom severity and reduced Pe with a diagnosis of schizophrenia versus other psychosis. Here, we test the stability of impaired error processing over a four-year follow-up and relationships with subdimensions of negative symptoms. The ERN and Pe were recorded from individuals with psychotic disorders twice: 79 individuals were assessed 15years after first hospitalization, and 69 were assessed at 19years; 59 (26 with schizophrenia, 33 with other psychotic disorders) had data at both assessments. At 19years the Pe was blunted in schizophrenia. The ERN and Pe exhibited temporal stability over the four years (r=0.59 and 0.60, respectively). Reduced ERN and Pe correlated with the negative symptom subdimensions of inexpressivity and avolition, respectively, and not with psychotic or disorganized symptoms. Moreover, 15-year ERN predicted an increase in inexpressivity by year 19. No evidence was found for the reverse: negative symptoms did not predict change in ERN/Pe. Similar to non-clinical samples, the ERN and Pe show impressive four-year stability in late-phase psychosis. The ERN and Pe are promising neural measures for capturing individual differences in psychotic disorders, particularly with regard to negative symptomatology. They may prove to be useful clinically for forecasting illness course and as treatment targets. [ABSTRACT FROM AUTHOR]

Background Reduced auditory target P300 amplitude is a leading biomarker for psychotic disorders, although its relevance for differential diagnosis and link to specific clinical features (symptom profiles, functional impairment, and course) are unclear. This study aims to clarify the clinical significance of auditory target P300 using concurrent and retrospective clinical data from a longitudinal cohort with psychosis. Methods 92 cases from an epidemiological study of first-admission psychosis were assessed using an auditory oddball paradigm at 15-year follow-up along with 44 never-psychotic adults. Subcomponents of auditory target P300 amplitude (i.e., a central positive P3a, a parietal positive P3b, and a frontal negative slow wave) were isolated using temporal–spatial principal component analysis. Results P3a amplitude was blunted across psychotic disorders relative to non-psychotic adults. P3b amplitude was reduced in schizophrenia specifically, including cases initially misclassified at baseline. The frontal negative slow wave did not distinguish among groups. P3b amplitude reduction was associated with several clinical features at the concurrent assessment, as well as previous time points, including recovery from psychosis even 5 years earlier and functioning even 15 years earlier. Conclusions Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may also shed light on prognosis, real-world functioning, and course, as well as help to reduce misdiagnosis of psychotic disorders. Prospective studies are needed to test whether P3b tracks or predicts clinical status. [ABSTRACT FROM AUTHOR]

• Cases with SCZ and other psychoses both showed cognitive impairments. • Cognitive impairment was more pronounced in those with SCZ than other psychoses. • Siblings of SCZ cases showed deficits in processing speed and executive function. • Siblings of cases with other psychoses showed no cognitive deficits. • Case status explained 6.5 times as much variance in cognition as specific diagnosis. People diagnosed with schizophrenia and other psychoses demonstrate impaired neuropsychological performance. Their unaffected siblings exhibit mild impairments relative to unrelated controls, suggesting genetic and shared environmental risk for psychosis account for some portion of cognitive impairments observed in cases. However, most sibling studies were conducted early in illness course. Studying cases and unaffected siblings later in life is valuable because diagnostic misclassification is common early in illness, possibly leading to spurious conclusions. This study compared neuropsychological performance of individuals with psychotic disorders (schizophrenia and other psychoses), their unaffected siblings, and controls. Assessments were conducted 20 years after case enrollment in the Suffolk County Mental Health Project, when siblings and controls were added to the protocol. Results showed individuals with schizophrenia and other psychoses performed worse than their matched siblings across domains. Relative to controls, siblings of participants with schizophrenia showed mild deficits in executive function and processing speed, while no significant differences were observed between siblings of those with other psychoses and controls. These findings suggest pre- and post-onset factors impact cognitive deficits in psychosis, but pre-onset factors are more salient in schizophrenia. Additionally, schizophrenia and other psychoses exist on a neurodevelopmental continuum, with schizophrenia being a more severe manifestation. [ABSTRACT FROM AUTHOR]