Nat Genet
November 2024
medRxiv
August 2024
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test).
View Article and Find Full Text PDFBiol Psychiatry Glob Open Sci
April 2023
Background: We investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk.
Methods: In two complementary adolescent samples where the majority reported minimal MJ use, we compared cognitive performances before and after MJ use initiation. The Iowa sample (40 first-degree relatives and 54 second-degree relatives of patients with schizophrenia and 117 control subjects with no schizophrenia family history) underwent a battery of standardized neuropsychological tests at 0, 18, and 36 months.
Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.
Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.
Hum Brain Mapp
January 2022
Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness.
View Article and Find Full Text PDFHum Brain Mapp
January 2022
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry.
View Article and Find Full Text PDFBackground: Schizophrenia (SZ) patients and their biological relatives are more impulsive than controls. Although greater impulsivity in SZ has been associated with dysfunction in prefrontal neural circuits implicated in reward processing, little is known regarding brain structural correlates of heightened impulsivity in unaffected adolescent relatives of SZ patients.
Methods: Impulsive decision-making was assessed using the delay discounting task in 174 adolescents: 36 first-degree relatives (FDR) and 50 second-degree relatives (SDR) of SZ patients, and 88 healthy controls with no SZ family history (NSFH).
Science
March 2020
Nat Genet
November 2019
Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions.
View Article and Find Full Text PDFJ Psychiatr Res
February 2018
Objective: Although schizophrenia is not a prototypic impulse-control disorder, patients report more impulsive behaviors, have higher rates of substance use, and show dysfunction in brain circuits that underlie impulsivity. We investigate impulsivity in unaffected biological relatives of schizophrenia patients to further understand the relationships between schizophrenia risk and impulse control during adolescence.
Method: Group differences in impulsivity (UPPS-P Impulsive Behavior Scale and delay discounting) were tested in 210 adolescents contrasting 39 first- and 53 second-degree biological relatives of schizophrenia patients, and 118 subjects with no schizophrenia family history (NSFH).
Nat Commun
January 2017
Nat Neurosci
December 2016
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals.
View Article and Find Full Text PDFSchizophrenia is a psychiatric disorder with high heritability. Recent genome-wide association studies have provided a list of risk loci reliably derived from unprecedentedly large samples. However, further delineation of the diagnosis-associated susceptibility variants is needed to better characterize the genetic architecture given the disease's complex nature.
View Article and Find Full Text PDFCurrently available treatments have limited efficacy in remediating cognitive impairment in schizophrenia. Efforts to facilitate cognition-enhancing drug discovery recommend the use of varied experimental cognitive paradigms (including relational memory) as assessment tools in clinical drug trials. Although relational memory deficits are increasingly being recognized as a reliable cognitive marker of schizophrenia, relational memory performance among unaffected biological relatives remains unknown.
View Article and Find Full Text PDFThe adolescent brain undergoes extensive structural white matter (WM) changes. Adolescence is also a critical time period during which cognitive, emotional and social maturation occurs in transition into adulthood. Compared to adults, adolescents are generally more impulsive with increased risk-taking behaviors.
View Article and Find Full Text PDFJ Int Neuropsychol Soc
February 2016
Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia.
View Article and Find Full Text PDFObjectives: Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study.
Methods: Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia.
Disruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity--as measured by fractional anisotropy (FA)--is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM abnormalities in schizophrenia are not localized to one specific brain region but instead reflect global low-level decreases in FA coupled with focal abnormalities.
View Article and Find Full Text PDFNature
April 2015
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
View Article and Find Full Text PDFBackground: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.
Methods: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls.
Brain Imaging Behav
June 2014
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects.
View Article and Find Full Text PDFThe neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia.
View Article and Find Full Text PDFOne application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute.
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