Familial Risk for Schizophrenia vs Bipolar Disorder and Task-Based Neural Activation: A functional Magnetic Resonance Imaging Meta-Analysis.

Background And Hypothesis: Individuals at familial risk for developing schizophrenia (FRSZ) or bipolar disorder (FRBD) have shared and unique genetic risks. Few studies have compared neural activation between these two groups. Therefore, the present meta-analysis investigated functional brain similarities and differences between FRSZ and FRBD individuals.

Symptoms of Attenuated Psychosis Syndrome in Relatives of Clinical High-Risk Youth: Preliminary Evidence.

Background And Hypothesis: Attenuated Psychosis Syndrome (APS) impacts functioning and predicts increased risk of psychosis. Risk for developing APS itself has received minimal attention. Knowledge of familial and environmental contributions to APS symptoms would advance understanding of APS and risk for psychosis.

Age-dependent effects of schizophrenia genetic risk on cortical thickness and cortical surface area: Evaluating evidence for neurodevelopmental and neurodegenerative models of schizophrenia.

Risk for schizophrenia peaks during early adulthood, a critical period for brain development. Although several influential theoretical models have been proposed for the developmental relationship between brain pathology and clinical onset, to our knowledge, no study has directly evaluated the predictions of these models for schizophrenia developmental genetic effects on brain structure. To address this question, we introduce a framework to estimate the effects of schizophrenia genetic variation on brain structure phenotypes across the life span.

Age-dependent patterns of schizophrenia genetic risk affect cognition.

Cognition shares substantial genetic overlap with schizophrenia, yet it remains unclear whether such genetic effects become significant during developmental periods of elevated risk for schizophrenia, such as the peak age of onset. We introduce an investigative framework integrating epidemiological, developmental, and genetic approaches to determine whether genetic effects shared between schizophrenia and cognition are significant across periods of differing risk for schizophrenia onset, and whether these effects are shared with depression. 771 European-American participants, including 636 (ages 15-84 years) from families with at least two first-degree relatives with schizophrenia and 135 unrelated controls, were divided into three age-risk groups based on ages relative to epidemiological age of onset patterns for schizophrenia: Pre-Peak (before peak age-of-onset: 15 to 22 years), Post-Peak (after peak age-of-onset: 23-42 years), and Plateau (during plateau of age-of-onset: over 42 years).

Why does age of onset predict clinical severity in schizophrenia? A multiplex extended pedigree study.

Schizophrenia has substantial variation in symptom severity, course of illness, and overall functioning. Earlier age of onset (AOO) is consistently associated with negative outcomes and yet the causes of this association are still unknown. We used a multiplex, extended pedigree design (total N = 771; 636 relatives from 43 multigenerational families with at least 2 relatives diagnosed with schizophrenia and 135 matched controls) to examine among the schizophrenia relatives (N = 103) the relationship between AOO and negative and positive symptom severity, cognition, and community functioning.

Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.

Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen's d≥0.

Cognition and community functioning in schizophrenia: The nature of the relationship.

Although cognition is one of the most important predictors of community functioning in schizophrenia, little is known about the causes of this correlation. To our knowledge, this study is the first to examine the extent to which this correlation is genetically mediated and whether the genetic correlation is specific to schizophrenia. Six hundred thirty-six participants from 43 multigenerational families with at least two relatives with schizophrenia and 135 unrelated controls underwent diagnostic interview and cognition and functioning assessment.

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance.

Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects.

Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk.

Schizophrenia is a mental disorder characterized by impairments in behavior, thought, and neurocognitive performance. We searched for susceptibility loci at a quantitative trait locus (QTL) previously reported for abstraction and mental flexibility (ABF), a cognitive function often compromised in schizophrenia patients and their unaffected relatives. Exome sequences were determined for 134 samples in 8 European American families from the original linkage study, including 25 individuals with schizophrenia or schizoaffective disorder.

Cognitive Enhancement Therapy in substance misusing schizophrenia: results of an 18-month feasibility trial.

Substance use is a frequent problem in schizophrenia, and although many substance misusing patients with the disorder also experience considerable cognitive impairments, such individuals have been routinely excluded from clinical trials of cognitive remediation that could support their functional and addiction recoveries. This study conducted a small-scale feasibility trial of Cognitive Enhancement Therapy (CET) in substance misusing schizophrenia patients to assess the feasibility and efficacy of implementing comprehensive neurocognitive and social-cognitive remediation in this population. A total of 31 schizophrenia outpatients meeting addiction severity criteria for alcohol and/or cannabis use were randomized to 18months of CET or usual care.

Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia.

Background: Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia, and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-multigenerational families with schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but these families have not been previously examined to study structural brain abnormalities. We estimate the heritability of subcortical and hippocampal brain volumes in multiplex-multigenerational families and the heritability of subregions using advanced shape analysis.

Neuroimaging predictors of cognitive performance across a standardized neurocognitive battery.

Objective: The advent of functional MRI (fMRI) enables the identification of brain regions recruited for specific behavioral tasks. Most fMRI studies focus on group effects in single tasks, which limits applicability where assessment of individual differences and multiple brain systems is needed.

Method: We demonstrate the feasibility of concurrently measuring fMRI activation patterns and performance on a computerized neurocognitive battery (CNB) in 212 healthy individuals at 2 sites.

Neurocognitive performance stability in a multiplex multigenerational study of schizophrenia.

Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia from unaffected family members and healthy comparison subjects. These deficits in neurocognitive performance in patients with schizophrenia appear stable in the short-term. However, the duration of most, but not all, longitudinal studies is modest and the majority have relied on traditional average performance measures to examine stability.

The nature of schizotypy among multigenerational multiplex schizophrenia families.

Identification of endophenotypes (Gottesman & Gould, 2003; Gottesman & Shields, 1972) that genetically correlate with schizophrenia and are genetically homogeneous is an important strategy for detecting genes that affect schizophrenia risk. Symptoms of schizotypy may familially correlate with schizophrenia; however, there are critical limitations of the current literature concerning this association. The present study examined the genetic architecture and genetic associations between schizotypy and schizophrenia among multigenerational, multiplex schizophrenia families.

Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families.

Objectives: Recent work shows promising associations between schizophrenia and polymorphisms in neuregulin-1 (NRG1) and a large literature also finds strong familial relationships between schizophrenia and cognitive deficits. Given the role of NRG1 in glutamate regulation and glutamate's effect on cognition, we hypothesized that cognitive deficits may be related to variation within NRG1, providing a possible mechanism to increase risk for schizophrenia.

Methods: This study examined the associations between NRG1, cognition, and schizophrenia using a multigenerational multiplex family sample (total N=419, 40 families), including 58 affected participants (schizophrenia or schizoaffective disorder-depressed type) and their 361 unaffected relatives.

A multivariate perspective on schizotypy and familial association with schizophrenia: a review.

Although generally accepted that schizotypal personality disorder diagnosis is more prevalent among relatives of individuals with schizophrenia and may be associated with genetic liability to schizophrenia, it seems likely that this diagnosis is itself heterogeneous and thus perhaps not as useful in identifying genes that affect schizophrenia risk (i.e. endophenotypes) as it could be.

Evidence of factorial variance of the Mayer-Salovey-Caruso Emotional Intelligence Test across schizophrenia and normative samples.

The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a key measure of social cognition recommended by the MATRICS committee. While the psychometric properties of the MSCEIT appear strong, previous evidence suggested its factor structure may have shifted when applied to schizophrenia patients, posing important implications for cross-group comparisons. Using multi-group confirmatory factor analysis, we explicitly tested the factorial invariance of the MSCEIT across schizophrenia (n=64) and two normative samples (n=2099 and 451).

RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.

Polymorphisms of the gene encoding the regulator of G protein signaling, subtype 4 (RGS4), may be associated with schizophrenia. Among first-episode schizophrenia patients, they are also associated with dorsolateral prefrontal cortex (DLPFC) volume. The DLPFC is a key region that regulates heritable cognitive functions implicated in schizophrenia pathogenesis.

Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia.

Background: Cognitive impairment in the form of decreased working memory and executive functions has been recognized as a key deficit in schizophrenia. Neurotropic viruses have been associated with focal gray matter deficits in patients with schizophrenia. We evaluated whether such agents alter cognitive function in schizophrenia.

Assessing social-cognitive deficits in schizophrenia with the Mayer-Salovey-Caruso Emotional Intelligence Test.

The emotion management subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) has recently been recommended by the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia committee as the sole measure of social cognition for trials of cognitive enhancement in schizophrenia, yet the psychometric properties of this subscale and the larger instrument in schizophrenia patients have not been thoroughly examined. This research presents a psychometric investigation of the MSCEIT in a sample of 64 early course outpatients with schizophrenia, schizoaffective, or schizophreniform disorder. Results demonstrated that the MSCEIT possesses adequate internal consistency reliability among its branch and total scales and that patients' branch and overall test performance was significantly below normative levels.

A genome screen for quantitative trait loci influencing schizophrenia and neurocognitive phenotypes.

Objective: Deficits in neurocognitive function have been demonstrated in individuals with schizophrenia and in the unaffected family members of these individuals. Genetic studies of such complementary traits, along with traditional analyses of diagnosis, may help to elucidate the biological pathways underlying familial liability to schizophrenia and related disorders. The authors conducted a multiplex, multigenerational family study using a genome-wide screen for schizophrenia and related neurocognitive phenotypes.

Development of social functioning in preschizophrenia children and adolescents: a systematic review.

Schizophrenia is associated with severe deficits in social functioning. Similar deficits may be present prior to psychosis onset, in childhood and adolescence. If so, then prepsychosis social deficits could provide clues to the development of pathological processes in preschizophrenia children and could potentially improve early identification of the disorder and suggest targets for intervention.

Spontaneous dyskinesia and familial liability to schizophrenia.

Several factors suggest that spontaneous dyskinesia may be a useful supplemental phenotype for further elucidating the specific nature of the genetic contribution to schizophrenia. For example, involuntary movement abnormalities have been observed in both medicated and unmedicated schizophrenia patients, in individuals with schizotypal personality disorder, and sometimes in siblings of schizophrenia patients. However, there are many inconsistencies present in the literature to date.