Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.

Phenotypic and genetic relationships between white matter microstructure (i.e., fractional anisotropy [FA]) and peripheral inflammatory responses (i.

Perceptual organization and task demands jointly shape auditory working memory capacity.

Listeners performed two different tasks in which they remembered short sequences comprising either complex tones (generally heard as one melody) or everyday sounds (generally heard as separate objects). In one, listeners judged whether a probe item had been present in the preceding sequence. In the other, they judged whether a second sequence of the same items was identical in order to the preceding sequence.

Cocktail-party listening and cognitive abilities show strong pleiotropy.

Introduction: The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors.

Impact of Copy Number Variants and Polygenic Risk Scores on Psychopathology in the UK Biobank.

Background: Our understanding of the impact of copy number variants (CNVs) on psychopathology and their joint influence with polygenic risk scores (PRSs) remains limited.

Methods: The UK Biobank recruited 502,534 individuals ages 37 to 73 years living in the United Kingdom between 2006 and 2010. After quality control, genotype data from 459,855 individuals were available for CNV calling.

Specificity of Psychiatric Polygenic Risk Scores and Their Effects on Associated Risk Phenotypes.

Background: Polygenic risk scores (PRSs) are indices of genetic liability for illness, but their clinical utility for predicting risk for a specific psychiatric disorder is limited. Genetic overlap among disorders and their effects on allied phenotypes may be a possible explanation, but this has been difficult to quantify given focus on singular disorders and/or allied phenotypes.

Methods: We constructed PRSs for 5 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder) and 3 nonpsychiatric control traits (height, type II diabetes, irritable bowel disease) in the UK Biobank ( = 31,616) and quantified associations between PRSs and phenotypes allied with mental illness: behavioral (symptoms, cognition, trauma) and brain measures from magnetic resonance imaging.

Genetic Overlap Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multisite Study of Multiplex Pedigrees.

Background: Cognitive impairment is a key feature of psychiatric illness, making cognition an important tool for exploring of the genetics of illness risk. It remains unclear which measures should be prioritized in pleiotropy-guided research. Here, we generate profiles of genetic overlap between psychotic and affective disorders and cognitive measures in Caucasian and Hispanic groups.

Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation.

Background: Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

Methods: Using data from 9,421 individuals aged 8-21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor.

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively.

Searching for Imaging Biomarkers of Psychotic Dysconnectivity.

Background: Progress in precision psychiatry is predicated on identifying reliable individual-level diagnostic biomarkers. For psychosis, measures of structural and functional connectivity could be promising biomarkers given consistent reports of dysconnectivity across psychotic disorders using magnetic resonance imaging.

Methods: We leveraged data from four independent cohorts of patients with psychosis and control subjects with observations from approximately 800 individuals.

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population.

Associations of cannabis use disorder with cognition, brain structure, and brain function in African Americans.

Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross-sectional community sample of 205 African Americans (age 18-70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi-domain cognitive measures and structural, diffusion, and resting state brain-imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing.

The reliability and heritability of cortical folds and their genetic correlations across hemispheres.

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established.

The architecture of co-morbidity networks of physical and mental health conditions in military veterans.

Co-morbidity between medical and psychiatric conditions is commonly considered between individual pairs of conditions. However, an important alternative is to consider all conditions as part of a co-morbidity network, which encompasses all interactions between patients and a healthcare system. Analysis of co-morbidity networks could detect and quantify general tendencies not observed by smaller-scale studies.

Minimal Relationship between Local Gyrification and General Cognitive Ability in Humans.

Previous studies suggest that gyrification is associated with superior cognitive abilities in humans, but the strength of this relationship remains unclear. Here, in two samples of related individuals (total N = 2882), we calculated an index of local gyrification (LGI) at thousands of cortical surface points using structural brain images and an index of general cognitive ability (g) using performance on cognitive tests. Replicating previous studies, we found that phenotypic and genetic LGI-g correlations were positive and statistically significant in many cortical regions.

Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology.

Aims/hypothesis: Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.

Methods: Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.

Results: Negative phenotypic correlations (ρ) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d']: ρ = -0.

Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation.

White matter microstructure is affected by immune system activity via the actions of circulating pro-inflammatory cytokines. Although white matter microstructure and inflammatory measures are significantly heritable, it is unclear if overlapping genetic factors influence these traits in humans. We conducted genetic correlation analyses of these traits using randomly ascertained extended pedigrees from the Genetics of Brain Structure and Function Study (N = 1862, 59% females, ages 18-97 years; 42 ± 15.