Severe deprivation in early childhood leads to permanent growth stunting: Longitudinal analysis of height trajectories from childhood-to-adulthood.

Background: Childhood institutional deprivation is associated with growth stunting in childhood but long-term effects in adulthood remain uncertain.

Objective: To examine the impact of global institutional deprivation experienced in early childhood on subsequent growth with a special focus on final adult height and puberty timing.

Participants & Setting: The study was originally set in the UK, though some adoptive families lived abroad by the time of the adult follow up.

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.

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.

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.

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.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis.

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

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure.

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype.

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

Background: Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection.

Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders.

First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone.

A Common Polymorphism in SCN2A Predicts General Cognitive Ability through Effects on PFC Physiology.

Here we provide novel convergent evidence across three independent cohorts of healthy adults (n = 531), demonstrating that a common polymorphism in the gene encoding the α2 subunit of neuronal voltage-gated type II sodium channels (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher "g" independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort (n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral PFC and dorsal ACC, which support higher cognitive functions.

Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts.

Mitochondrial DNA mutations and cognition: a case-series report.

Mutations in the mitochondrial genome can impair normal metabolic function in the central nervous system (CNS) where cellular energy demand is high. Primary mitochondrial DNA (mtDNA) mutations have been linked to several mitochondrial disorders that have comorbid psychiatric, neurologic, and cognitive sequelae. Here, we present a series of cases with primary mtDNA mutations who were genotyped and evaluated across a common neuropsychological battery.

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

Importance: One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation.

Objective: To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals.

Design, Setting, And Participants: Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples.

Moderator effects of working memory on the stability of ADHD symptoms by dopamine receptor gene polymorphisms during development.

We tested the hypothesis that dopamine D1 and D2 receptor gene (DRD1 and DRD2, respectively) polymorphisms and the development of working memory skills can interact to influence symptom change over 10 years in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, we examined whether improvements in working memory maintenance and manipulation from childhood to early adulthood predicted the reduction of ADHD symptoms as a function of allelic variation in DRD1 and DRD2. Participants were 76 7-11-year-old children with ADHD who were genotyped and prospectively followed for almost 10 years.

Association between variation in neuropsychological development and trajectory of ADHD severity in early childhood.

Objective: This longitudinal study examined if changes in neuropsychological functioning were associated with the trajectory of symptoms related to attention deficit hyperactivity disorder (ADHD) and impairment between preschool and school age.

Method: The sample consisted of 3- and 4-year-old children (N=138) who were identified as being at risk for ADHD based on parent and teacher reports. Neuropsychological functioning was measured annually using the NEPSY at four time points (mean ages, 4.

Effects of the BDNF Val66Met polymorphism on white matter microstructure in healthy adults.

The BDNF Val(66)Met polymorphism, a possible risk variant for mental disorders, is a potent modulator of neural plasticity in humans and has been linked to deficits in gray matter structure, function, and cognition. The impact of the variant on brain white matter structure, however, is controversial and remains poorly understood. Here, we used diffusion tensor imaging to examine the effects of BDNF Val(66)Met genotype on white matter microstructure in a sample of 85 healthy Caucasian adults.

Perceptual and motor inhibition in adolescents/young adults with childhood-diagnosed ADHD.

Objective: This study examined perceptual and motor inhibition in a longitudinal sample of adolescents/young adults who were diagnosed with ADHD in childhood, and as a function of the relative persistence of ADHD.

Method: Ninety-eight participants diagnosed with ADHD in childhood were reevaluated approximately 10 years later. Eighty-five never-ADHD controls similar in age, IQ, sociodemographic background, and gender distribution served as a comparison group.

Childhood maltreatment and conduct disorder: independent predictors of adolescent substance use disorders in youth with attention deficit/hyperactivity disorder.

Children with attention deficit/hyperactivity disorder (ADHD) are at heightened risk for maltreatment and later substance use disorders (SUDs). We investigated the relationship of childhood maltreatment and other risk factors to SUDs among adolescents diagnosed with ADHD in childhood. Eighty adolescents diagnosed with ADHD when they were 7 to 11 years old were screened for histories of childhood maltreatment, and SUD diagnoses were formulated in accordance with the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders.

The impact of childhood ADHD on dropping out of high school in urban adolescents/ young adults.

Objective: To examine cognitive and psychosocial factors associated with high school dropout in urban adolescents with and without childhood ADHD.

Method: In a longitudinal study, 49 adolescents/young adults with childhood ADHD and 44 controls who either dropped out or graduated from high school are included. Risk factors examined as potential correlates of dropout were intelligence, reading skills, socioeconomic status, marijuana use, and paternal contact.

Neuropsychological outcome in adolescents/young adults with childhood ADHD: profiles of persisters, remitters and controls.

Background: This study examined neuropsychological functioning in a longitudinal sample of adolescents/young adults with attention deficit/hyperactivity disorder (ADHD) and controls as a function of the persistence of ADHD. We hypothesized that measures of executive processes would parallel adolescent clinical status, with ADHD-persisters, but not remitters, differing significantly from controls. In contrast, persisters and remitters were hypothesized to perform similarly, and different from controls, on tasks requiring less effortful processing.