Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated With Psychopathology Across Independent Cohorts.

Background: Patients with early psychosis (EP) (within 3 years after psychosis onset) show significant variability, which makes predicting outcomes challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, which limits the development of early interventions.

Methods: A data-driven approach, partial least squares correlation, was used across 2 independent datasets to examine multivariate relationships between white matter properties and symptomatology and to identify stable and generalizable signatures in EP.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions.

Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP.

Multivariate Associations Among White Matter, Neurocognition, and Social Cognition Across Individuals With Schizophrenia Spectrum Disorders and Healthy Controls.

Background And Hypothesis: Neurocognitive and social cognitive abilities are important contributors to functional outcomes in schizophrenia spectrum disorders (SSDs). An unanswered question of considerable interest is whether neurocognitive and social cognitive deficits arise from overlapping or distinct white matter impairment(s).

Study Design: We sought to fill this gap, by harnessing a large sample of individuals from the multi-center Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) dataset, unique in its collection of advanced diffusion imaging and an extensive battery of cognitive assessments.

Metabolic disturbances, hemoglobin A1c, and social cognition impairment in Schizophrenia spectrum disorders.

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HbA1c) > 6.

Contributions of Parasympathetic Arousal-Related Activity to Cognitive Performance in Patients With First-Episode Psychosis and Control Subjects.

Background: Cognitive impairment is integral to the pathophysiology of psychosis. Recent findings implicate autonomic arousal-related activity in both momentary fluctuations and individual differences in cognitive performance. Although altered autonomic arousal is common in patients with first-episode psychosis (FEP), its contribution to cognitive performance is unknown.

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets.

Social Cognitive Networks and Social Cognitive Performance Across Individuals With Schizophrenia Spectrum Disorders and Healthy Control Participants.

Background: Schizophrenia spectrum disorders (SSDs) feature social cognitive deficits, although their neural basis remains unclear. Social cognitive performance may relate to neural circuit activation patterns more than to diagnosis, which would have important prognostic and therapeutic implications. The current study aimed to determine how functional connectivity within and between social cognitive networks relates to social cognitive performance across individuals with SSDs and healthy control participants.

Overlapping Neurobiological Substrates for Early-Life Stress and Resilience to Psychosis.

Early-life stress, such as childhood maltreatment, is a well-known etiological factor in psychopathology, including psychosis. Exposure to early-life stress disrupts the neurodevelopment of widespread brain systems, including key components of the hypothalamic-pituitary-adrenal axis stress response, such as the amygdala, hippocampus, and medial prefrontal cortex, as well as key components of the brain's reward system, such as the nucleus accumbens and orbitofrontal cortex. These disruptions have a considerable impact on the function of emotion and reward circuitry, which play a central role in the emergence and severity of psychosis.

Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response.

Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs.

History of childhood maltreatment is associated with reduced fractional anisotropy of the accumbofrontal 'reward' tract in healthy adults.

The deleterious outcomes associated with exposure to childhood maltreatment (CM) are well known and may be at least partially mediated by self-harm behaviors. It has been suggested that these self-harm behaviors serve as a means of decreasing negative mood states but the effects of CM on health outcomes may be much more sinister. A wealth of data suggest that CM may lead to experience-dependent changes in neural circuits underlying reward processes; processes associated with many harmful behaviors.

Parasympathetic arousal-related cortical activity is associated with attention during cognitive task performance.

Parasympathetic arousal is associated with states of heightened attention and well-being. Arousal may affect widespread cortical and subcortical systems across the brain, however, little is known about its influence on cognitive task processing and performance. In the current study, healthy adult participants (n ​= ​20) underwent multi-band echo-planar imaging (TR ​= ​0.

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results.

Striatal volume and functional connectivity correlate with weight gain in early-phase psychosis.

Second-generation antipsychotic drugs (SGAs) are essential in the treatment of psychotic disorders, but are well-known for inducing substantial weight gain and obesity. Critically, weight gain may reduce life expectancy for up to 20-30 years in patients with psychotic disorders, and prognostic biomarkers are generally lacking. Even though other receptors are also implicated, the dorsal striatum, rich in dopamine D2 receptors, which are antagonized by antipsychotic medications, plays a key role in the human reward system and in appetite regulation, suggesting that altered dopamine activity in the striatal reward circuitry may be responsible for increased food craving and weight gain.

Deconstructing Avolition: Initiation vs persistence of reward-directed effort.

Avolition, a decrease in the initiation and persistence of goal-directed behavior, is a critical determinant of disability in patients with schizophrenia. Recent studies have demonstrated that avolition can be modeled using reward-based, behavioral paradigms. These studies suggest that avolition represents a motivational deficit, accounted for by a diminished ability to anticipate pleasurable experiences.

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Structural similarity networks predict clinical outcome in early-phase psychosis.

Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.

Separable and Replicable Neural Strategies During Social Brain Function in People With and Without Severe Mental Illness.

Objective: Case-control study design and disease heterogeneity may impede biomarker discovery in brain disorders, including serious mental illnesses. To identify biologically and/or behaviorally driven as opposed to diagnostically driven subgroups of individuals, the authors used hierarchical clustering to identify individuals with similar patterns of brain activity during a facial imitate/observe functional MRI task.

Methods: Participants in the Social Processes Initiative in Neurobiology of the Schizophrenia(s) study (N=179; 109 with a schizophrenia spectrum disorder and 70 healthy control participants) underwent MRI scanning at three sites.

Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study.

Objective: The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks.

Methods: A total of 502 healthy participants (aged 11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors.

The Role of Executive Function in Adolescent Adaptive Risk-Taking on the Balloon Analogue Risk Task.

The present study examined the role of executive control functions (ECF) in adaptive risk-taking during adolescence. Healthy individuals aged 8-25 were administered ECF measures and the Balloon Analogue Risk Task (BART), a computerized measure of risk-taking propensity. Findings demonstrated that adolescents who executed a more consistent response strategy evidenced better performance on the BART.

Frequency specific resting state functional abnormalities in psychosis.

Resting state functional magnetic resonance imaging studies of psychosis have focused primarily on the amplitude of low-frequency fluctuations in the blood oxygen level dependent (BOLD) signal ranging from .01 to 0.1 Hz.

Affective modulation of target detection in deficit and non-deficit schizophrenia.

Emotional deficits are an integral feature of schizophrenia (SZ), but our understanding of these deficits is limited. In the present study, we examined whether the severity of emotional deficits reflects difficulty in the cognitive processing of affectively valenced stimuli. Healthy controls (HC; N = 170) and stable outpatients with SZ (N = 245), characterized as either deficit syndrome (DS; N = 62) or non-deficit syndrome (NDS; N = 183), completed an Affective Go/NoGo task requiring discrimination of positively, negatively or neutrally valenced words.

Lower- and Higher-Level Social Cognitive Factors Across Individuals With Schizophrenia Spectrum Disorders and Healthy Controls: Relationship With Neurocognition and Functional Outcome.

Background: Schizophrenia spectrum disorders (SSDs) often feature social cognitive deficits. However, little work has focused on the factor structure of social cognition, and results have been inconsistent in schizophrenia. This study aimed to elucidate the factor structure of social cognition across people with SSDs and healthy controls.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol.