Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals.

Measuring Cognitive Impairments Associated With Schizophrenia in Clinical Practice: Overview of Current Challenges and Future Opportunities.

Background: Cognitive impairment associated with schizophrenia (CIAS) negatively impacts daily functioning, quality of life, and recovery, yet effective pharmacotherapies and practical assessments for clinical practice are lacking. Despite the pivotal progress made with establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for clinical research, implementation of the full MCCB is too time-consuming and cost-ineffective for most clinicians in clinical practice.

Study Design: Here we discuss current assessments in relation to delivery format (interview-based and performance-based), validity, ease of use for clinicians and patients, reliability/reproducibility, cost-effectiveness, and suitability for clinical implementation.

Defeatist performance beliefs in individuals with recent-onset schizophrenia: Relationships with cognition and negative symptoms.

Background: The cognitive model of negative symptoms of schizophrenia suggests that defeatist performance beliefs (DPB), or overgeneralized negative beliefs about one's performance, are an intermediary variable along the pathway from impaired neurocognitive performance to negative symptoms and functioning in daily life. Although reliable associations between these variables have been established in chronic schizophrenia, less is known about the nature of these relationships in recent-onset schizophrenia (ROSz). This current study tested the associations between DPB and variables in the cognitive model (neurocognitive performance, negative symptoms, functioning) as well as mediation by DPB of the association between neurocognitive performance and negative symptoms in ROSz.

Task-based default mode network connectivity predicts cognitive impairment and negative symptoms in first-episode schizophrenia.

Individuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in "source monitoring" have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self-generated and externally generated events is disrupted.

Intrinsic motivation predicts cognitive and functional gains during coordinated specialty care for first-episode schizophrenia.

Coordinated Specialty Care (CSC) and embedded group therapeutic interventions have been effective in improving outcomes for individuals experiencing recent first-episode schizophrenia, including cognitive performance and functioning. Treatment response varies substantially, with some patients experiencing limited or no improvement. Motivation has emerged as a key determinant of treatment engagement and efficacy.

Exercise behaviours and motivation after a first psychotic episode: A digital intervention.

Aim: Research has demonstrated that participation in aerobic exercise can have significant beneficial effects across both physical and mental health domains for individuals who are in the early phase of schizophrenia. Despite these notable benefits of exercise, deficits in motivation and a lack of methods to increase engagement are significant barriers for exercise participation, limiting these potentially positive effects. Fortunately, digital health tools have the potential to improve adherence to an exercise program.

The relationship between sex and functional outcome in first-episode schizophrenia: the role of premorbid adjustment and insight.

Background: Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences.

Methods: Our sample consisted of 137 individuals with first episode schizophrenia (males, = 105; 77%) with a mean age of 22.

Clarifying directional dependence among measures of early auditory processing and cognition in schizophrenia: leveraging Gaussian graphical models and Bayesian networks.

Background: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing.

Prospective, randomized, multicenter clinical trial evaluating longitudinal changes in brain function and microstructure in first-episode schizophrenia patients treated with long-acting injectable paliperidone palmitate versus oral antipsychotics.

Widespread anatomical alterations and abnormal functional connectivity have shown strong association with symptom severity in first-episode schizophrenia (FES) patients. Second-generation antipsychotic treatment might slow disease progression and possibly modify the cerebral plasticity in FES patients. However, whether a long-acting injectable antipsychotic (paliperidone palmitate [PP]), available in monthly and every-3-months formulations, is more effective than oral antipsychotics (OAP) in improving cerebral organization has been unclear.

Exercise Predicts a Good Night's Sleep: Preliminary Findings from a UCLA Study of First-Episode Schizophrenia.

Background: Physical exercise can improve sleep quality in the general population. Understanding the negative impact of poor sleep quality on multiple domains of functioning among persons with schizophrenia is a new frontier of exploration. It is also imperative to investigate non-pharmacologic methods to improve sleep quality as these approaches may not carry the side effect burdens associated with medication.

Treatment engagement in first-episode schizophrenia: Associations between intrinsic motivation and attendance during cognitive training and an aerobic exercise program.

Systematic cognitive training and aerobic exercise programs have emerged as promising interventions to improve cognitive deficits in first-episode schizophrenia, with successful outcomes closely linked with greater treatment engagement (e.g., higher attendance and homework completion rates).

Developmental trajectories of premorbid functioning predict cognitive remediation treatment response in first-episode schizophrenia.

Background: Cognitive development after schizophrenia onset can be shaped by interventions such as cognitive remediation, yet no study to date has investigated whether patterns of early behavioral development may predict later cognitive changes following intervention. We therefore investigated the extent to which premorbid adjustment trajectories predict cognitive remediation gains in schizophrenia.

Methods: In a total sample of 215 participants (170 first-episode schizophrenia participants and 45 controls), we classified premorbid functioning trajectories from childhood through late adolescence using the Cannon-Spoor Premorbid Adjustment Scale.

The MATRICS Consensus Cognitive Battery: An Update.

Through a series of NIMH-supported consensus-building meetings of experts and empirical comparisons of candidate tests, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative developed a battery of standardized cognitive measures to allow reliable evaluation of results from clinical trials of promising interventions for core cognitive deficits in this disorder. Ten tests in seven cognitive domains were selected for the MATRICS Consensus Cognitive Battery (MCCB). The MCCB has now been translated into 39 languages/dialects and has been employed in more than 145 clinical trials.

Dispersion of cognitive performance test scores on the MATRICS Consensus Cognitive Battery: A different perspective.

Objective: Persons with schizophrenia exhibit greater neurocognitive test score dispersion. Here, we seek to characterize dispersion on the Neurocognitive Composite subtests of the Measurement of Treatment Research to Improve Cognition in Schizophrena Consensus Cognitive Battery (MCCB) and determine the relative effects of different antipsychotic formulations on dispersion and mean performance.

Method: In this post hoc analysis of the DREaM study (NCT02431702), which compared treatment with paliperidone palmitate (PP) long-acting injectable with oral antipsychotic (OAP) treatment over 18 months, dispersion in MCCB neurocognitive subtest performance was calculated for each participant by visit (test occasion).

Aerobic exercise enhances cognitive training effects in first-episode schizophrenia: randomized clinical trial demonstrates cognitive and functional gains.

Background: Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.

Understanding Connections and Boundaries Between Positive Symptoms, Negative Symptoms, and Role Functioning Among Individuals With Schizophrenia: A Network Psychometric Approach.

Importance: Improved understanding of the boundaries and connections between positive symptoms, negative symptoms, and role functioning in schizophrenia is critical, given limited empirical support for clear distinctions among these clinical areas. This study's use of network psychometrics to investigate differential associations and structural overlap between positive symptoms, negative symptoms, and functional domains in schizophrenia may contribute to such understanding.

Objective: To apply network analysis and community detection methods to examine the interplay and structure of positive symptoms, negative symptoms, and functional domains in individuals with schizophrenia.

Evaluation of major treatment failure in patients with recent-onset schizophrenia or schizophreniform disorder: A post hoc analysis from the Disease Recovery Evaluation and Modification (DREaM) study.

Objective: A post hoc analysis of the Disease Recovery Evaluation and Modification (DREaM) study was conducted to evaluate time to first major treatment failure (ie, arrest/incarceration or psychiatric hospitalization) in participants with recent-onset schizophrenia or schizophreniform disorder treated with paliperidone palmitate (PP) versus oral antipsychotics (OAPs).

Methods: DREaM was an open-label, delayed-start, randomized, multipart trial consisting of: Part I, 2-month oral run-in; Part II, 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (PP/PP; OAP re-randomized: OAP/OAP or OAP/PP). PP/PP and OAP/OAP comprised the 18-month extended disease progression (EDP) analysis.

Value-directed remembering in first-episode schizophrenia.

Objective: Memory deficits in individuals with schizophrenia are well-established, but less is known about how schizophrenia affects metacognitive processes such as metamemory. We investigated metamemory ability using the value-directed remembering task, which assesses the degree to which participants use value cues to guide their learning of a list of items (i.e.

The Disease Recovery Evaluation and Modification (DREaM) study: Effectiveness of paliperidone palmitate versus oral antipsychotics in patients with recent-onset schizophrenia or schizophreniform disorder.

We report primary results of the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial designed to compare the effectiveness of paliperidone palmitate (PP) versus oral antipsychotics (OAP) in delaying time to first treatment failure (TtFTF) in participants with recent-onset schizophrenia or schizophreniform disorder. DREaM included: Part I, 2-month oral run-in; Part II, 9-month disease progression phase (PP or OAP); Part III, 9 months of additional treatment (PP/PP; OAP rerandomized: OAP/OAP or OAP/PP). PP/PP and OAP/OAP comprised the 18-month extended disease progression (EDP) analysis.

Confident memory errors and disrupted reality testing in early psychosis.

Schizophrenia is a psychiatric disorder characterized by a disruption in reality testing most often manifest in the form of delusions and hallucinations. Because determining the reality-basis of prior experiences is dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. In the present study, we used an associative memory paradigm incorporating confidence ratings to examine whether patients with a recent onset of schizophrenia (n = 48) show a greater propensity for confident, yet incorrect responses during retrieval testing than healthy controls (n = 26) and whether such confident incorrect responses, specifically, are more strongly associated with positive symptoms than with negative symptoms.

Linguistic and neurocognitive correlates of probabilistic classification learning in schizophrenia.

Individuals with schizophrenia demonstrate impaired implicit learning on cognitively complex tasks and preserved implicit motor learning. However, little is known about how implicit learning may be related to other linguistic and cognitive variables, including development of complex language including comprehension and syntax. This study explored the relationship between probabilistic classification learning, a type of implicit learning style, and linguistic and cognitive skills in schizophrenia.

Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia.

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.

Cortical morphometric correlational networks associated with cognitive deficits in first episode schizophrenia.

Schizophrenia (SCZ) is a chronic cognitive and behavioral disorder associated with abnormal cortical activity during information processing. Several brain structures associated with the seven performance domains evaluated using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) have shown cortical volume loss in first episode schizophrenia (FES) patients. However, the relationship between morphological organization and MCCB performance remains unclear.