Contents Vol. 2, 2016
Mol Neuropsychiatry 2016;2:I-IV (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - February 2, 2017 Category: Neuroscience Source Type: research
Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort
This study represents the first large-scale DNA sequencing project designed to assess the role of rare functional genetic variation in suicidal behavior risk. To accomplish this, whole-exome sequencing data for ∼19,000 genes were generated for 387 bipolar disorder subjects with a history of suicide attempt and 631 bipolar disorder subjects with no prior suicide attempts. Rare functional variants were assessed in all exome genes as well as pathways hypothesized to contribute to suicidal behavior risk. No result survived conservative Bonferroni correction, though many suggestive findings have arisen that merit additional a...
Source: Molecular Neuropsychiatry - January 17, 2017 Category: Neuroscience Source Type: research
Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry
This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.Mol Neurops...
Source: Molecular Neuropsychiatry - January 12, 2017 Category: Neuroscience Source Type: research
Evidence of AS3MTd2d3-Associated Variants within 10q24.32-33 in the Genetic Risk of Major Affective Disorders
Genome-wide association studies suggest that 10q24.32-33 is a risk region for schizophrenia (SCZ). Considering the substantial genetic overlap between SCZ and major affective disorders, we would like to investigate whether the 10q24.32-33 region confers risk of affective disorders. We chose three SCZ genome-wide significant SNPs (rs7914558, rs7085104, and rs11191580) in 10q24.32-33 and collected the statistical data from European and Asian populations to perform systematic meta-analyses, which finally included up to 26,413 cases with affective disorders and 24,849 controls. Meta-analyses showed that all SNPs were nominally...
Source: Molecular Neuropsychiatry - December 14, 2016 Category: Neuroscience Source Type: research
Evidence of AS3MT < sup > d2d3 < /sup > -Associated Variants within 10q24.32-33 in the Genetic Risk of Major Affective Disorders
Genome-wide association studies suggest that 10q24.32-33 is a risk region for schizophrenia (SCZ). Considering the substantial genetic overlap between SCZ and major affective disorders, we would like to investigate whether the 10q24.32-33 region confers risk of affective disorders. We chose three SCZ genome-wide significant SNPs (rs7914558, rs7085104, and rs11191580) in 10q24.32-33 and collected the statistical data from European and Asian populations to perform systematic meta-analyses, which finally included up to 26,413 cases with affective disorders and 24,849 controls. Meta-analyses showed that all SNPs were nominally...
Source: Molecular Neuropsychiatry - December 14, 2016 Category: Neuroscience Source Type: research
Positive Traits in the Bipolar Spectrum: The Space between Madness and Genius
Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. Creativity is a complex, multidimensional construct with ...
Source: Molecular Neuropsychiatry - December 8, 2016 Category: Neuroscience Source Type: research
Pharmacogenetic Analysis of Functional Glutamate System Gene Variants and Clinical Response to Clozapine
We report no significant associations following correction for multiple testing. Prior to correction, nominally significant associations were observed forSLC6A9,SLC1A2,GRM2, andGRIA1. Most notably, CC homozygotes of rs16831558 located in the glycine transporter 1 gene(SLC6A9) exhibited an allele dose-dependent improvement in positive symptoms compared to T allele carriers (puncorrected = 0.008, pcorrected = 0.08). To clarify the role ofSLC6A9 in clinical response to antipsychotic medication, and CLZ in particular, this finding warrants further investigation in larger well-characterized samples.Mol Neuropsychiatry 2016;2:18...
Source: Molecular Neuropsychiatry - October 11, 2016 Category: Neuroscience Source Type: research
Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31
To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotyp...
Source: Molecular Neuropsychiatry - October 11, 2016 Category: Neuroscience Source Type: research
Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins
Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes.N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ...
Source: Molecular Neuropsychiatry - September 19, 2016 Category: Neuroscience Source Type: research
Oxytocin Receptor (OXTR) Methylation and Cognition in Psychotic Disorders
Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor(OXTR). Within psychotic disorders, it is unknown ifOXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral bloodOXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101)...
Source: Molecular Neuropsychiatry - August 15, 2016 Category: Neuroscience Source Type: research
Oxytocin Receptor < b > < i > (OXTR) < /i > < /b > Methylation and Cognition in Psychotic Disorders
Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor(OXTR). Within psychotic disorders, it is unknown ifOXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral bloodOXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101)...
Source: Molecular Neuropsychiatry - August 12, 2016 Category: Neuroscience Source Type: research
A Rare Variant in CACNA1D Segregates with 7 Bipolar I Disorder Cases in a Large Pedigree
Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. WithinCACNA1D, a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree. A high-resolution DNA denaturing curve method was then used to screen for the presence of the A1751P change in 4,150 BPI cases from the NIMH...
Source: Molecular Neuropsychiatry - August 3, 2016 Category: Neuroscience Source Type: research
A Rare Variant in < b > < i > CACNA1D < /i > < /b > Segregates with 7 Bipolar I Disorder Cases in a Large Pedigree
Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. WithinCACNA1D, a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree. A high-resolution DNA denaturing curve method was then used to screen for the presence of the A1751P change in 4,150 BPI cases from the NIMH...
Source: Molecular Neuropsychiatry - August 2, 2016 Category: Neuroscience Source Type: research
A Mutation in NPAS3 That Segregates with Schizophrenia in a Small Family Leads to Protein Aggregation
In this study, we demonstrate that NPAS3 is prone to aggregation, and that the V304I mutation in NPAS3 increases this propensity in both bacterial and mammalian expression systems. We also show that NPAS3-V304I reduces soluble endogenous NPAS3, and increases insoluble endogenous NPAS3 and leads to alteration of transcriptional activity. These results suggest that protein aggregation, potentially leading to cell dysfunction via a loss of protein function through sequestration, may contribute to the pathogenesis of schizophrenia and other forms of mental illness. Further exploration of the mechanisms leading to abnormal prot...
Source: Molecular Neuropsychiatry - July 26, 2016 Category: Neuroscience Source Type: research
Dopamine D2L Receptor Is Required for Visual Discrimination and Reversal Learning
The corticostriatothalamic circuit regulates learning behaviors via dopamine neurotransmission. D2 long (D2L) receptors are an isoform of dopamine D2 receptors (D2Rs) and may act mainly at postsynaptic sites. It is well known that D2Rs influence high brain functions, but the roles of individual D2R isoforms are still unclear. To assess the influence of D2L receptors in visual discrimination learning, we performed visual discrimination and reversal tasks with D2L knockout mice using a touchscreen operant system. There were no significant differences in an operant conditioning task between genotypes. However, D2L knockout mi...
Source: Molecular Neuropsychiatry - July 20, 2016 Category: Neuroscience Source Type: research
