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Multidimensional progressive declines in the absence of standard biomarkers for neurodegeneration are observed commonly in the development of schizophrenia, and are accepted as consistent with neurodevelopmental etiological hypotheses to explain the origins of the disorder. Far less accepted is the possibility that neurodegenerative processes are involved as well, or even that key dimensions of function, such as cognition and aspects of biological integrity, such as white matter function, decline in chronic schizophrenia beyond levels associated with normal aging. We propose that recent research germane to these issues warrants a current look at the question of neurodegeneration. We propose the view that a neurodegenerative hypothesis provides a better explanation of some features of chronic schizophrenia, including accelerated aging, than is provided by neurodevelopmental hypotheses. Moreover, we suggest that neurodevelopmental influences in early life, including those that may extend to later life, do not preclude the development of neurodegenerative processes in later life, including some declines in cognitive and biological integrity. We evaluate these views by integrating recent findings in representative domains such as cognition and white and gray matter integrity with results from studies on accelerated aging, together with functional implications of neurodegeneration for our understanding of chronic schizophrenia. [ABSTRACT FROM AUTHOR]

The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions. [ABSTRACT FROM AUTHOR]

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded “milder” SZ phenotypes than those acquired subsequently in the COGS-2 case–control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. [ABSTRACT FROM AUTHOR]

Objective: Studies in healthy individuals show that exerting self-control consumes cognitive resources, which reduces subsequent self-control performance. Restoring the availability of blood glucose eliminates this impairment. Patients with schizophrenia are found to have self-regulatory dysfunctions. This study aims to investigate whether patient's (a) glucose facilitation effects will be impaired, and (b) will have exaggerated depletion in a self-control task. Method: 40 patients with schizophrenia-spectrum disorders and 40 normal controls were recruited. A two drinks (glucose vs. placebo)×two depleting phases (self-control depleted vs. non-depleted) between-groups design was used. We examined the blood glucose levels before and after the selfcontrol depletion phase and the subsequent performances in two self-control tasks (handgrip and Stroop tests) after the drink condition. Results: The four groups (depleting×glucose, depleting×placebo, non-depleting×glucose and nondepleting×placebo) of both patients and normal controls were comparable on a number of characteristics. The change in blood glucose level in the depleting group was significantly different from those in the non-depleting group. Two×two between-subjects ANOVAs were carried out to test the performances in the handgrip and Stroop tasks. Significant interactions were found in healthy controls regarding both tasks. However, a significant interaction was only found in patients regarding the handgrip task but not the Stroop task. Conclusions: This study demonstrated an abnormal glucose facilitation effect in patients during a cognitive self-control task but not during a physical self-control task. The findings also suggested for the first time that a self-control depletion effect is intact in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study–identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p <.005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships. [ABSTRACT FROM AUTHOR]

Abstract: Cognitive deficits are among the most important factors leading to poor functional outcomes in schizophrenia, with deficits in declarative memory among the largest and most robust of these. Thus far, attempts to enhance cognition in schizophrenia have shown only modest success, which underlies increasing efforts to develop effective treatment strategies. This review is divided into three main parts. The first section delineates the nature and extent of the deficits in both patients with schizophrenia and in their adult, non-psychotic relatives. The second part focuses on structural and functional abnormalities in the hippocampus, both in people with schizophrenia and in animal studies that model relevant features of the illness. The third section views problems in declarative memory and hippocampal function from the perspective of elevated rates of common medical disorders in schizophrenia, with a focus on insulin insensitivity/diabetes. The likelihood that poor glucose regulation/availability contribute to declarative memory deficits and hippocampal abnormalities is considered, along with the possibility that schizophrenia and poor glucose regulation share common etiologic elements, and with clinical implications of this perspective for enhancing declarative memory. [Copyright &y& Elsevier]

Abstract: Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. [Copyright &y& Elsevier]

Abstract: Verbal declarative memory is one of the most reliably impaired cognitive functions in schizophrenia. Important issues are whether the problem is reversible, and which brain regions underlie improvement. We showed previously that glucose administration improved declarative memory in patients with schizophrenia, and sought in this pilot study to identify whether glucose affects the location or degree of activation of brain regions involved in a verbal encoding task. Seven clinically stable and medicated patients with schizophrenia or schizoaffective disorder, who showed deficits on a clinical test of memory, participated in the study. Subjects served as their own controls in a double-blind, crossover protocol that consisted of two sessions about a week apart. In each session, subjects ingested a beverage flavored with lemonade that contained 50g of glucose on one occasion, and saccharin on the other. Blood glucose was measured before and 15, 50, and 75min after ingestion. After ingesting the beverage, they performed a verbal encoding task while undergoing brain functional magnetic resonance imaging. The results showed significantly greater activation of the left parahippocampus during novel sentence encoding in the glucose condition, compared to the saccharin condition, despite no change in memory performance. A trend towards greater activation of the left dorsolateral prefrontal cortex (p<.07) was also evident in the glucose condition. These pilot findings emphasize the sensitivity of both the medial temporal and prefrontal regions to effects of glucose administration during encoding, and are consistent with the hypothesis that these regions also participate in declarative memory improvements following glucose administration. [Copyright &y& Elsevier]

Clozapine has been shown to improve verbal declarative memory and other cognitive functions in chronic schizophrenia. This raises the possibility that additional adjunctive manipulations might improve memory further. In this study, we hypothesized that glucose, which improves memory in a variety of conditions, including schizophrenia, would improve memory more than saccharin in a group of patients stabilized on clozapine. Twelve outpatients with schizophrenia who received treatment with clozapine participated in a double-blind, counterbalanced, crossover study. Subjects received beverages containing either glucose or saccharin on one occasion, and then the other beverage about a week later. Fifteen minutes after ingesting the beverage, subjects received a brief battery of neuropsychological tests to assess verbal declarative memory, attention, and executive functions. Blood glucose levels were assessed at baseline, and at 15 and 50 min after beverage ingestion. The main findings were that retention of a list of words was improved in the glucose condition, while performance on a complex test of sustained vigilance declined after glucose ingestion. These findings provide evidence that glucose improves declarative memory in patients with schizophrenia who were treated with clozapine, and underscore the possibility of developing effective protocols to reduce cognitive dysfunctions in the disorder. They also highlight the need to explore the extent to which glucose modulates nonmemory cognitive functions such as attention, and to understand more generally how glucose availability and regulation influence cognition. [Copyright &y& Elsevier]

Examines the obstacles in the prevention and treatment of schizophrenia in Canada. Identification of the syndrome; Response to antipsychotic medications; Concept of schizotaxia.

The liability to schizophrenia (schizotaxia) is associated with deficits in a variety of domains, including negative symptoms and neuropsychological deficits, even in the absence of psychosis or pre-psychotic prodromal symptoms. Conceptually, this view of schizotaxia is similar to negative schizotypy (i.e., schizotypal personality disorder minus the positive symptoms). It is broader than DSM-IV schizotypal personality disorder (SPD), however, in that more relatives of patients with schizophrenia show core symptoms of schizotaxia than meet the diagnostic criteria for SPD. Three lines of evidence support the validity of schizotaxia. First, evidence of concurrent validation was obtained by showing that schizotaxic subjects were more impaired than non-schizotaxic subjects on a variety of independent clinical scales. Second, schizotaxic subjects showed higher levels of negative symptoms on the Structured Interview for Schizotypy than non-schizotaxic subjects, but did not differ on positive symptoms. Third, subjects who met predetermined criteria for schizotaxia (i.e., negative symptoms and neuropsychological deficits) showed positive effects following treatment with low doses of risperidone (0.25–2.0 mg). Thus, clinical deficits in schizotaxia may be identifiable, and to a significant extent, reversible. Implications for the conception of schizotypy and the prevention of schizophrenia will be discussed. [Copyright &y& Elsevier]

Assesses the implications of DSM criteria for schizophrenia by reviewing the criteria's emphasis on psychotic features, dissociation of symptoms from their etiology, exclusive reliance on clinical features and classification of schizophrenia as a discrete category. Alternative conceptions of schizophrenia that take into account data concerning its genetic and neurodevelopmental origins.

Dysfunction in cortico-striatal circuitry represents a core component of the pathophysiology in schizophrenia (SZ) but its potential as a candidate endophenotype of the illness is often confounded by neuroleptic medication. Accordingly, 26 adolescent and young adult participants at genetic high-risk for schizophrenia, but who were asymptomatic and neuroleptic naïve, and 28 age-matched controls underwent 1.5T structural magnetic resonance imaging of the striatum, manually parcellated into limbic (LST), associative (AST), and sensorimotor (SMST) functional subregions. In relation to their age peers, participants at genetic high-risk for schizophrenia showed overall lower striatal gray matter volume with their most pronounced loss, bilaterally in the AST, but not the LST or SMST. Neuropsychological testing revealed reduced executive functioning for genetically at-risk participants, although the groups did not differ significantly in overall intelligence or oral reading. For controls but not for at-genetic high-risk participants, stronger executive functioning correlated with increased bilateral AST volume. Reduced bilateral AST volume in genetic high-risk adolescents and young adults, accompanied by heritable loss of higher cognitive brain-behavior relationships, might serve as a useful endophenotype of SZ. [ABSTRACT FROM AUTHOR]

Clinical high risk of psychosis (CHR-P) population has become an attractive area of interest in preventing transitions to psychosis. The consequences of developing a psychotic disorder may be worse in cases of early onset. Thus, childhood and adolescence represent a critical developmental window, where opportunities to gain social and adaptive abilities depend on the individuals' neurocognitive performance. There have been previous syntheses of the evidence regarding neurocognitive functioning in CHR-P individuals and its longitudinal changes. However, there has been less focus on children and adolescents at CHR-P. A multistep literature search was performed from database inception until July 15th, 2022. PRIMSA/MOOSE compliant systematic review and PROSPERO protocol were used to identify studies reporting on longitudinal changes in neurocognitive functioning in children and adolescents (mean age of sample ≤ 18 years) at CHR-P and matched healthy control (HC) group. A systematic review of identified studies was then undertaken. Three articles were included, resulting in a total sample size of 151 CHR-P patients [mean (SD) age, 16.48 (2.41) years; 32.45% female] and 64 HC individuals [mean (SD) age, 16.79 (2.38) years; 42.18% female]. CHR-P individuals had worse outcomes in verbal learning, sustained attention and executive functioning domains compared to HC. Individuals taking antidepressants had better outcomes in verbal learning in contrast with those taking antipsychotics. In children and adolescents, neurocognition may be already impaired before the psychosis onset, and remains stable during the transition to psychosis. Further study should be performed to obtain more robust evidence. [ABSTRACT FROM AUTHOR]

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHR P) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning. [ABSTRACT FROM AUTHOR]

Hippocampal volume (HV) is sensitive to environmental influences. Under normative conditions in humans, HV increases linearly into childhood and asymptotes in early adulthood. Studies of humans and nonhuman animals have provided evidence of inverse relationships between several measures of stress and HV. Using structural equation modeling, this study aimed to characterize the relationships of age, basal cortisol, biological sex, and lifetime perceived stress with bilateral HV in a sample of healthy adolescents and adolescents at clinical high risk for psychosis (CHR-P) (N = 571, 43% female; age range = 12–19.9 years). This sample included 469 individuals at CHR-P and 102 healthy comparison participants from the combined baseline cohorts of the second and third NAPLS (North American Prodrome Longitudinal Study). A structural model that constrained the individual effects of basal cortisol and perceived stress to single path coefficients, and freely estimated the effects of age and biological sex in group models, optimized model fit and parsimony relative to other candidate models. Significant inverse relationships between basal cortisol and bilateral HV were observed in adolescents at CHR-P and healthy comparison participants. Significant sex differences in bilateral HV were also observed, with females demonstrating smaller HV than males in both groups. Multigroup structural equation modeling revealed heterogeneity in the relationships of age and biological sex with basal cortisol, lifetime perceived stress, and bilateral HV in individuals at CHR-P and healthy comparison participants. Moreover, the findings support previous literature indicating that elevated basal cortisol is a nonspecific risk factor for reduced HV. [ABSTRACT FROM AUTHOR]

Despite the complexities of schizophrenia, notable progress has been achieved in its diagnosis and treatment over the last 25 years. In this article we review the genetic research that provides the foundation for continued advances. One of the bases of our current understanding involves the observation that schizophrenia often runs in families. The development and utilization of stringent, reliable diagnostic criteria, together with the advent of modern family, twin, and adoption paradigms, demonstrate the importance of genetic factors in understanding the familial basis of the disorder. Refinements in diagnostic criteria have also enabled advances in understanding the likely mode--or modes--of genetic transmission of both schizophrenia and related disorders. After reviewing representative studies in these areas, we examine genetic linkage studies and our progress toward identifying the genes that cause schizophrenia. Although consistent results have been difficult to obtain and much work remains to be done, evidence for areas of vulnerability has been converging at particular chromosomal sites (e.g., 6p, 8p, and 22q), allowing for cautious optimism. Finally, we discuss challenges and prospects for the new millennium, including the clinical and ethnical implications of genetic investigations. [ABSTRACT FROM AUTHOR]

• Negative symptoms impact quality of life and functioning. • Complement regulators and coagulation regulators are prognostic factors of negative symptoms. • Their prognostic value is independent of clinical and demographic prognostic factors. • These results may aid early intervention for negative symptoms of psychosis. Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (β: 0.501, 95 % CI: 0.160, 0.842; β: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (β: 0.501, 95 % CI: −0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (β: 0.442, 95 % CI: 0.127, 0.757). The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk. [ABSTRACT FROM AUTHOR]

The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium's transdiagnostic dimensional model of psychopathology has considerable support; however, this model has been underresearched in individuals at clinical high risk for psychosis (CHR-P), a population that may advance the model. CHR-P individuals not only have attenuated psychotic symptoms that vary in severity, but also have many comorbid diagnoses and varied clinical outcomes, including disorders with uncertain relations to HiTOP (e.g., obsessive-compulsive disorder). The present study used self-report and interview data from North American Prodrome Longitudinal Study-3 (710 CHR, 96 controls) to replicate the HiTOP model and test specific hypotheses regarding disorders with uncertain relations to its dimensions. Additionally, the present study examined the HiTOP model in relation to childhood trauma, declines in social functioning, and development of full psychosis. Confirmatory factor analysis indicated that the HiTOP model's fit was nearly adequate (e.g., comparative fit index =.89), though several theory-relevant modifications were indicated. Additionally, specific tests were conducted to gain a more fine-grained perspective on how disorders with less clear prior evidence were related to the HiTOP model. Notable findings from these analyses include bipolar spectrum disorders relating to the psychosis super spectrum (i.e.,.39 loading), and obsessive-compulsive disorder showing a complex pattern of loadings (e.g., internalizing and psychosis). The final model parsimoniously accounted for childhood trauma (e.g., super spectra rs =.22–.32), associations with current functioning, and predicted future conversion to a psychotic disorder (e.g., super spectra R2 =.13). Overall, these results inform the HiTOP model and suggest its promise for CHR-P research. General Scientific Summary: Individuals at risk of developing psychosis often have multiple psychiatric diagnoses; however, existing diagnostic frameworks poorly describe the reality of the symptoms experienced by individuals at risk for psychosis. The present study supported the validity and utility of an alternative framework for describing psychiatric symptoms—the Hierarchical Taxonomy of Psychopathology—by showing its relevance to both psychosis risk factors and clinical outcomes. [ABSTRACT FROM AUTHOR]

The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Methods: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. Results: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). Conclusions: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Recent studies show that computer-based training enhances cognition in schizophrenia; furthermore, socialization has also been found to improve cognitive functions. It is generally believed that non-social cognitive remediation using computer exercises would be a pre-requisite for therapeutic benefits from social cognitive training. However, it is also possible that social interaction by itself enhances non-social cognitive functions; this possibility has scarcely been explored in schizophrenia patients. This pilot study examined the effects of computer-based neurocognitive training, along with social interaction either with a peer (PSI) or without one (N-PSI). We hypothesized that PSI will enhance cognitive performance during computerized exercises in schizophrenia, as compared with N-PSI.Methods: Sixteen adult participants diagnosed with schizophrenia or schizoaffective disorder participating in an ongoing trial of Cognitive Enhancement Therapy completed several computerized neurocognitive remediation training sessions (the Orientation Remedial Module©, or ORM), either with a peer or without a peer.Results: We observed a significant interaction between the effect of PSI and performance on the different cognitive exercises (p<0.05). More precisely, when patients performed the session with PSI, they demonstrated better cognitive performances than with N-PSI in the ORM exercise that provides training in processing speed, alertness, and reaction time (the standard Attention Reaction Conditioner, or ARC) (p<0.01, corrected). PSI did not significantly affect other cognitive domains such as target detection and spatial attention.Conclusion: Our findings suggest that PSI could improve cognitive performance, such as processing speed, during computerized cognitive training in schizophrenia. Additional studies investigating the effect of PSI during cognitive remediation are needed to further evaluate this hypothesis. [ABSTRACT FROM AUTHOR]

The article focuses on the sensitivity of schizophrenia endophenotype biomarkers to anticholinergic medication burden (ACMB). Topics include the impact of ACMB on cognitive performance in individuals with schizophrenia, the role of neurophysiological biomarkers (MMN and P3a) in early auditory information processing, and the association between ACMB and diminished MMN and P3a responses in schizophrenia patients.

While individuals at clinical high-risk (CHR) for psychosis experience higher levels of discrimination than healthy controls, it is unclear how these experiences contribute to the etiology of attenuated positive symptoms. The present study examined the association of perceived discrimination with positive symptoms in a cohort from the North American Prodrome Longitudinal Study (NAPLS2). It predicted that CHR individuals will report higher levels of lifetime and past year perceived discrimination related to their race and ethnicity (ethnoracial discrimination) and that this form of discrimination will be significantly associated with baseline positive symptoms. Participants included 686 CHR and 252 healthy controls. The present study examined data from the perceived discrimination (PD) scale, the Brief Core Schema Scale, and the Scale for the Psychosis-Risk Symptoms. Structural equation modeling was employed to examine whether negative schema of self and others mediated the relation of past year ethnoracial PD to baseline suspiciousness symptoms. CHR individuals report higher levels of past year and lifetime PD compared to healthy controls. Lifetime ethnoracial PD was associated with suspiciousness and total positive symptoms. Negative schema of self and others scores partially mediated the relation of past year ethnoracial PD to suspiciousness, one of five positive symptom criteria for CHR. For CHR individuals, past year ethnoracial discrimination was associated with negative beliefs about themselves and others, which was associated with suspiciousness. These findings contribute to an emerging literature characterizing the mechanisms by which discrimination contributes to the positive symptoms characterizing the CHR syndrome. [ABSTRACT FROM AUTHOR]

The article "Correction: Longitudinal change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis: a systematic review" published in the European Child & Adolescent Psychiatry journal discusses a correction regarding the affiliation details of Author Borja Pedruzo. The correction clarifies that the correct affiliation should include the Neuroscience Department at the University of Basque Country (UPV/EHU) in addition to the Department of Psychiatry at Basurto University Hospital in Bilbao, Spain. The original article has been updated to reflect this correction. [Extracted from the article]

• Adverse childhood experiences are highly associated with depression. • Childhood adversity is a risk factor for suicide attempts and substance use. • Childhood adversity was not linked to history of an anxiety disorder in this sample. • There are strikingly low levels of protective factors in high-risk youth samples. Research has established that adverse childhood experiences (ACEs) confer risk for psychiatric diagnoses, and that protective factors moderate this association. Investigation into the effect of protective factors in the relationship between ACEs and internalizing disorders (e.g., depression, anxiety) is limited in high-risk groups. The present study investigated the relationship between ACEs and risk for internalizing disorders in youth at clinical high risk for psychosis (CHR-P) and tests the hypothesis that protective factors moderate this relationship. 688 participants aged 12–30 (M = 18; SD = 4.05) meeting criteria for CHR-P were administered measures of child adversity, protective factors (SAVRY), and diagnostic assessment (SCID- 5). Logistic regression tested whether ACEs predicted internalizing disorders. Moderation regression analyses determined whether these associations were weaker in the presence of protective factors. Higher levels of ACEs predicted history of depressive disorder (β = 0.26(1.30), p <.001), self-harm/suicide attempts (β = 0.34(1.40), p <.001), and substance use (β = 0.14(1.15), p =.04). Childhood sexual abuse (β = 0.77(2.15), p =.001), emotional neglect (β = 0.38(1.46), p =.05), and psychological abuse (β = 0.42(1.52), p =.04), predicted self- harm/suicide attempts. Sexual abuse (β = 1.00 (2.72), p =.001), and emotional neglect (β = 0.53(1.71), p =.011), were also linked to depressive disorder. There was no association between ACEs and anxiety disorder, and no moderation effect of protective factors in the relationship between ACEs and psychiatric outcomes. These findings add nuance to a growing literature linking ACEs to psychopathology and highlight the importance of investigation into the mechanisms that may buffer this relationship. [ABSTRACT FROM AUTHOR]

• Individuals at clinical high risk for psychosis (CHR-P) have increased sleep disruption. • Sleep disturbance was associated with concurrent SI in a large CHR-P sample. • Sleep problems were also associated with greater psychopathology. • Treating sleep disturbances to reduce suicidality is important in CHR-P. Insomnia and suicidal ideation (SI) are common in schizophrenia, including in individuals at clinical high-risk for psychosis (CHR-P). Previous studies have found associations between sleep disturbance, SI, and psychopathology in schizophrenia. We explored these associations in a CHR-P cohort. We leveraged data from CHR-P individuals in the North American Prodrome Longitudinal Studies (NAPLS-3) (n = 688) cohort. We investigated relationships between sleep disturbance (Scale of Prodromal Symptoms [SOPS]; Calgary Depression Scale for Schizophrenia [CDSS], and the Pittsburgh Sleep Quality Index [PSQI]), suicidal ideation (CDSS), and psychosis-risk symptoms. The prevalence of terminal insomnia, sleep disturbance, and SI in NAPLS3 was 25 %, 69 %, and 29 %, respectively. After controlling for potential confounders, multiple indices of sleep disturbance (SOPS, PSQI: OR = 1.05–1.40) were significant indicators of concurrent SI. Terminal insomnia was not associated with conversion to psychosis. Multiple indices of sleep problems were associated with higher total and subscale psychosis-risk symptom scores (β = 0.09–0.39). Sleep problems are prevalent and associated with SI and more severe psychosis-risk symptoms in CHR-P individuals. These findings underscore the importance of designing longitudinal intervention studies to investigate whether the treatment of sleep disturbances may reduce suicidality and symptoms in this population. [ABSTRACT FROM AUTHOR]

Aim: Individuals at clinical high risk (CHR) for psychosis have been shown to experience more trauma than the general population. However, although the effects of trauma appear to impact some symptoms it does not seem to increase the risk of transition to psychosis. The aim of this article was to examine the prevalence of trauma, and its association with longitudinal clinical and functional outcomes in a large sample of CHR individuals. Methods: From the North American Prodrome Longitudinal Study‐3 (NAPLS‐3) 690 CHR individuals and 91 healthy controls from nine study sites between 2015 and 2018 were assessed. Historical trauma experiences were captured at baseline. Participants completed longitudinal assessments measuring clinical outcomes including positive and negative symptoms, depression, social and role functioning and assessing transition to psychosis. Results: From the 690 CHR participants and 96 healthy controls, 343 (49.6%) and 15 (15.6%), respectively, reported a history of trauma (p <.001). Emotional neglect (70.3%) was the most commonly reported type of trauma, followed by psychological abuse (57.4%). Among CHR participants, time to transition to psychosis was not associated with trauma. Baseline depression and suspiciousness/persecutory ideas were statistically significantly different between CHR individuals who did or did not experience trauma. However, when examining clinical and functional outcomes over 12‐months of follow‐up, there were no differences between those who experienced trauma and those who did not. Conclusion: Overall, trauma is a significantly prevalent among CHR individuals. The effects of trauma on transition and longitudinal clinical and functional outcomes were not significant. [ABSTRACT FROM AUTHOR]

Background: Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling. Methods: We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as 'successfully completed' or 'incomplete'. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China. Results: In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age ('educated-younger' v. 'undereducated-older') show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant. Conclusions: We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. Methods: Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). Results: In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. Conclusions: Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to document the trajectory of weight gain and body mass index (BMI) in children with type 1 narcolepsy, and to analyze basal metabolic rate (BMR).Methods: A total of 65 Chinese children with type 1 narcolepsy with a disease duration ≤12 months were included. In addition, 79 healthy age-matched students were enrolled as controls. Height and body weight were measured every six months for up to 36 months to calculate BMI growth. BMR was measured using COSMED K4b2 indirect calorimetry in 34 patients and 30 healthy controls at six months. At the end of 36 months, the BMR was compared among 18 patients and 16 healthy controls.Results: The children with type 1 narcolepsy showed higher BMIs at follow-up assessments. At the end of the study, 38.46% of the patients were obese and an additional 26.15% were overweight. The patients' BMI growth at six, 12, 18, 24 and 30 months of follow-up was significantly higher, but not at month 36. The patients' basal energy expenditure was significantly lower than that of the controls at six months but not at 36 months.Conclusion: BMI increased rapidly in children with type 1 narcolepsy after disease onset, but BMI growth decreased gradually with prolonged disease. Decreased BMR is an important cause underlying rapid weight gain. The gradual restoration of BMI growth and BMR in narcolepsy emphasizes the importance of compensatory metabolic mechanisms in this disease. [ABSTRACT FROM AUTHOR]

Cannabis use is more prevalent among youth at clinical high-risk (CHR) for psychosis than healthy controls (HC). There is mixed evidence as to whether cannabis use is associated with increased severity of attenuated psychotic symptoms (APS) or whether current cannabis use is associated with the transition to psychosis. This study aims to assess cannabis use differences between CHR youth and HC and the impact of cannabis use on APS, clinical status, and transition to psychosis. Participants were from the North American Prodrome Longitudinal Study-3, a prospective longitudinal study including 710 individuals, age 12-30, meeting criteria for a psychosis risk syndrome based on the Structured Interview for Psychosis-Risk Syndromes, and 96 HC. Cannabis use, frequency, and severity of use were assessed with the Alcohol Use Scale/Drug Use Scale. Current and past cannabis use disorders were assessed with the Structured Clinical Interview for DSM-5. Compared to HC, CHR individuals reported significantly increased lifetime cannabis use, during the past six months, and at baseline; greater frequency and severity of cannabis use; and increased prevalence of cannabis use disorder. Relative to CHR youth without cannabis use, CHR cannabis users had significantly higher ratings on baseline grandiosity and lower 12-months social anhedonia. Severity of cannabis was unrelated to clinical status at 2-years, and it did not differentiate CHR individuals who transitioned to psychosis from those who did not. However, a major limitation was that the current number of CHR cannabis users was small, and survival analyses resulted in a smaller power than the 80 % recommended. [ABSTRACT FROM AUTHOR]

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

Aims: Young people with attenuated psychotic symptoms (APS), brief intermittent psychosis, and/or genetic risk and functional deterioration are at high risk for developing psychotic disorders. In a prior trial, family‐focused therapy for clinical high risk youth (FFT‐CHR) was more effective than brief psychoeducation in reducing APS severity over 6 months. This 7‐site trial will compare the efficacy of FFT‐CHR to a psychoeducational and supportive intervention (enhanced care) on APS and social functioning in CHR individuals over 18 months. Methods: Participants (N = 220, ages 13–25 years) with a CHR syndrome will be randomly assigned to FFT‐CHR (18 1‐h sessions of family psychoeducation and communication/problem‐solving skills training) or enhanced care (3 1‐h family psychoeducational sessions followed by 5 individual support sessions), both given over 6 months. Participants will rate their weekly progress during treatment using a mobile‐enhanced online platform. Family communication will be assessed in a laboratory interactional task at baseline and post‐treatment. Independent evaluators will assess APS (primary outcome) and psychosocial functioning (secondary outcome) every 6 months over 18 months. Results: We hypothesize that, compared to enhanced care, FFT‐CHR will be associated with greater improvements in APS and psychosocial functioning over 18 months. Secondarily, improvements in family communication over 6 months will mediate the relationship between treatment condition and primary and secondary outcomes over 18 months. The effects of FFT‐CHR are predicted to be greater in individuals with higher baseline risk for psychosis conversion. Conclusions: Results of the trial will inform treatment guidelines for individuals at high risk for psychosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Our study was designed to assess symptomatology and occurrences of narcolepsy in Eastern China between 2003 and 2012. Herein we report the substantial changes in the occurrence and clinical features of narcolepsy over the last decade in China. Methods: We performed a retrospective analysis of 162 Han Chinese patients with narcolepsy at Changzheng Hospital, Shanghai, China. Clinical histories and precipitating factors were recorded, in addition to narcolepsy and H1N1 winter flu pandemic (pH1N1) occurrences at Changzheng Hospital. The occurrences also were compared between the Changzheng Hospital and the People’s Hospital, Beijing, China. Results: In our sample, narcolepsy occurred 1.73 times more frequently in men than in women. Most of the participants were children, which peaked to 91% in 2010. Excessive daytime sleepiness (EDS), disrupted nocturnal sleep, cataplexy, and weight gain were the four major symptoms. We found that 40% of patients had identifiable precipitating factors. The occurrence of narcolepsy in 2010 showed an approximate three-fold difference from the baseline levels at the Changzheng Hospital, which showed positive relationships with occurrences of pH1N1 in Shanghai and the occurrence of narcolepsy at the People’s Hospital. Conclusions: Our findings show the interactive effects of geography and H1N1 disease in relation to narcolepsy in Han Chinese populations, and strengthen the theoretic hypothesis that immune and mental factors facilitate the onset of narcolepsy. [Copyright &y& Elsevier]

Introduction: Area-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with reduced gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral anterior cingulate cortex (rACC). We hypothesize that greater ARI will be associated with reduced right CMFG and rACC GMVs.Methods: Data were collected at baseline as part of the North American Prodrome Longitudinal Study Phase 2. Counties where participants resided during childhood were geographically coded using the US Census to area-level factors. ARI was defined as the percentage of residents living in a different house 5 years ago. Generalized linear mixed models tested associations between ARI and GMVs.Results: This study included 29 healthy controls (HC)s and 64 clinical high risk for psychosis (CHR-P) individuals who were aged 12 to 24 years, had remained in their baseline residential area, and had magnetic resonance imaging scans. ARI was associated with reduced right CMFG (adjusted β = -0.258; 95% CI = -0.502 to -0.015) and right rACC volumes (adjusted β = -0.318; 95% CI = -0.612 to -0.023). The interaction term (ARI-by-diagnostic group) in the prediction of both brain regions was not significant, indicating that the relationships between ARI and regional brain volumes held for both CHR-P and HCs.Conclusions: ARI may adversely impact similar brain regions as urban upbringing. Further investigation into the potential mechanisms of the relationship between ARI and neurobiology, including social stress, is needed. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia and affective psychoses share several common biological origins, particularly genetic susceptibility. Kraepelin posited that differing clinical expressions in these disorders reflect different etiopathologies. We tested a neuropsychological component of this hypothesis by evaluating verbal memory and visual memory performance in nonpsychotic youth at familial risk for psychosis, taking into account contributions to memory dysfunction including executive processing and psychopathology.Methods: Teenage and young adults (ages 13-25) at familial high-risk (FHR) for schizophrenia (HR-SCZ, n=41) or affective psychosis (HR-AFF, n=24) were compared to community controls (CC, n=54) on verbal (Miller-Selfridge Context Memory) and visual (Rey-Osterrieth Complex Figure) memory tests in which the roles of strategy and contextual processing on distinct recall domains could be assessed. Effects of psychopathology, vigilance and working memory were investigated to determine their influence on memory performance.Results: HR-AFF and HR-SCZ exhibited similarly impaired memory profiles and elevated levels of psychopathology compared to CC. HR-SCZ were significantly impaired on both verbal memory and visual-spatial memory, while HR-AFF in verbal memory only. However, effect sizes, in the medium range, were largely comparable between the two HR groups. Deficits in verbal recall and in visual memory organization remained significant after adjustment for confounders.Conclusions: Youth at FHR for psychosis present relatively common memory deficits across both visual-spatial and verbal modalities that are not explained by current psychopathology, vigilance or working memory deficits. Deficits in organizing information to be recalled represent a promising trait of psychosis vulnerability. [ABSTRACT FROM AUTHOR]

Abstract: Background: Schizophrenia and affective psychoses share several common biological origins, particularly genetic susceptibility. Kraepelin posited that differing clinical expressions in these disorders reflect different etiopathologies. We tested a neuropsychological component of this hypothesis by evaluating verbal memory and visual memory performance in nonpsychotic youth at familial risk for psychosis, taking into account contributions to memory dysfunction including executive processing and psychopathology. Methods: Teenage and young adults (ages 13–25) at familial high-risk (FHR) for schizophrenia (HR-SCZ, n=41) or affective psychosis (HR-AFF, n=24) were compared to community controls (CC, n=54) on verbal (Miller–Selfridge Context Memory) and visual (Rey–Osterrieth Complex Figure) memory tests in which the roles of strategy and contextual processing on distinct recall domains could be assessed. Effects of psychopathology, vigilance and working memory were investigated to determine their influence on memory performance. Results: HR-AFF and HR-SCZ exhibited similarly impaired memory profiles and elevated levels of psychopathology compared to CC. HR-SCZ were significantly impaired on both verbal memory and visual–spatial memory, while HR-AFF in verbal memory only. However, effect sizes, in the medium range, were largely comparable between the two HR groups. Deficits in verbal recall and in visual memory organization remained significant after adjustment for confounders. Conclusions: Youth at FHR for psychosis present relatively common memory deficits across both visual–spatial and verbal modalities that are not explained by current psychopathology, vigilance or working memory deficits. Deficits in organizing information to be recalled represent a promising trait of psychosis vulnerability. [Copyright &y& Elsevier]

Learning objectives: After participating in this CME activity, the clinician will be better able to: • Interpret classifications of neuropsychiatric systemic lupus erythematosus (NPSLE). • Identify determining factors of neuropsychiatric events. • Analyze current evidence regarding disease pathways for NPSLE. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence supports an association between residential instability and increased risk for psychosis, but the association between residential instability and conversion to psychosis among adolescents at clinical high risk (CHR) is unclear. In this study, we determined whether individual-level and area-level residential instability and their interaction are associated with conversion to psychosis within two years.Methods: Data were collected as part of the North American Prodrome Longitudinal Study Phase 2. Individual-level residential instability, defined as having ever moved during lifetime, was derived from the Life Events Scale. Area-level residential instability, defined as the percentage of people who were not living in the same house five years ago, was derived from the U.S. Decennial Censuses.Results: This study included 285 adolescents at CHR (including 36 subjects who later converted to full psychosis). We found that individual-level residential instability was associated with conversion (adjusted OR = 2.769; 95% CI = 1.037-7.393). The interaction between individual-level and area-level residential instability was significant (p = 0.030). In a subgroup of CHR participants who have never moved (n = 91), area-level residential instability during childhood was associated with conversion (adjusted OR = 1.231; 95% CI = 1.029-1.473). Conversely, in a subgroup of CHR participants who resided in residentially stable areas during childhood (n = 142), the association between individual-level residential instability and conversion remained significant (adjusted OR = 15.171; 95% CI = 1.753-131.305).Conclusions: These findings suggest that individual-level and area-level residential instability may be associated with conversion to psychosis. [ABSTRACT FROM AUTHOR]

Abstract: The current study examined characteristics of coping patterns adopted by college students in mainland China. In particular, it examined the coping strategies adopted by subjects with schizotypal personality (SPD) features compared to those without SPD features, and compared the relative effectiveness of their coping. Four types of coping flexibility were identified among the college sample (n =427), including active-inflexible, passive-inflexible, active-inconsistent, and passive-inconsistent styles. The passive-inconsistent style was related to the worst outcomes. When comparing subjects with SPD features with those without SPD features, subjects with SPD features endorsed significantly more emotion-focused strategies in uncontrollable situations than those without SPD features. The SPD group experienced higher levels of trait anxiety, depression, paranoid ideation and general health problems. The SPD group also generally perceived more, less controllable stress than the non-SPD group and randomly used all four categories of coping strategies. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To clarify effects of partial sleep deprivation (SD) on morning (07:00) serum cortisol concentrations in two protocols that restricted sleep to 3h/day in healthy adult men. The study was also designed to delineate the relationship between anxiety levels in the morning and slow wave sleep (SWS) periods at night. Methods: Ten young adult Han Chinese males were recruited to participate in an ‘earlier-night’ sleep restriction (SR) period (sleep from 00:00 to 03:00) and then a ‘later-night’ SR period (sleep from 03:00 to 06:00). The duration of each SR period was 4 days, followed by a recovery night. The SR periods were separated by 10 days of normal sleep. Blood samples of serum cortisol were drawn at 07:00 during each of two SR periods for six consecutive mornings (for a total of 12 measurements per subject), and anxiety levels were also assessed over the same period by the State portion of the State-Trait Anxiety Inventory (STAI). Sleeping processes were monitored by polysomnogram. Results: Serum cortisol levels decreased after SR (P <0.05) in both paradigms, with greater decreases evident after later-night sleep loss than after earlier-night sleep loss. Cortisol levels were significantly, negatively correlated to the number of days of earlier-night SR, but not to later-night SR. Anxiety scores increased gradually in both conditions. The time of SWS changed indiscriminately in both paradigms. Cortisol levels returned to baseline after one night of recovery sleep. Conclusions: Cortisol decreased in both SR conditions, especially in the earlier-night SR protocol, even though SWS time and anxiety levels changed roughly in the same manner in both conditions. Data suggested that sleep loss at different times of the night affects the hypothalamic–pituitary–adrenal axis (HPA-axis) differentially. [Copyright &y& Elsevier]

Objective: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.Methods: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).Results: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.Conclusions: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia. [ABSTRACT FROM AUTHOR]

The percentage of individuals who are functionally bilingual in the United States has grown substantially in the last 3 to 4 decades. Nevertheless, bilingual mental health providers remain relatively scarce and bilingualism in psychosis or schizophreniaspectrum disorders remains relatively unexplored. Here, we present a clinical case study of a man with schizophrenia who presented his psychotic symptoms differently in his primary and secondary languages. We also consider this case in the context of other published cases with similar themes. Based on our review, we hypothesize that the presentation of psychotic symptoms may be influenced by the language a person uses, and more specifically, by their cognitive abilities to speak that language and/or their emotional attachment to that language. We outline the importance of obtaining a thorough language background of each patient with psychosis and investigate the ways in which a second language could serve as a protective factor against functional decline in psychotic and healthy populations. We suggest that attempts to engage bilingual patients with psychosis clinically in each language could lead to a more holistic evaluation of psychotic and disorganized symptoms and thus lead to more multidimensional intervention strategies. [ABSTRACT FROM AUTHOR]

Objective: Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits. Participants and Methods: Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%). Results: A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2). Conclusions: Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes. [ABSTRACT FROM AUTHOR]

Background: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program. Method: In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC. Results: The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal. Conclusions: The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention. [ABSTRACT FROM AUTHOR]