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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]

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: 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]

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]

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]

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]

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]