Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes
This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD). Method: Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment. Blood RNA samples were collected at baseline and after 2 and 8 weeks of treatment. RNA expression was measured using the Affymetrix GeneChip® Human Gene 1.0 ST Array followed by Ingenuity pathways analysis. The results for the contrast of weeks 2 and 8 were not significantly different a...
Source: Molecular Neuropsychiatry - June 28, 2016 Category: Neuroscience Source Type: research
The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain
The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue fro...
Source: Molecular Neuropsychiatry - June 24, 2016 Category: Neuroscience Source Type: research
Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder
Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects sh...
Source: Molecular Neuropsychiatry - June 24, 2016 Category: Neuroscience Source Type: research
Leukocyte Telomere Length Predicts SSRI Response in Major Depressive Disorder: A Preliminary Report
Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, including major depressive disorder (MDD). Short LTL has previously been associated with poor response to psychiatric medications in bipolar disorder and schizophrenia, but no studies have prospectively assessed the relationship of LTL to selective serotonin reuptake inhibitor (SSRI) response in MDD. We assessed pre-treatment LTL, depression severity [using the Hamilton Depression Rating Scale (HDRS)], and self-reported positive and negative affect in 27 healthy, unmedicated adults with MDD. The subjects then underwent open-label tr...
Source: Molecular Neuropsychiatry - June 21, 2016 Category: Neuroscience Source Type: research
Neuregulin 3 Knockout Mice Exhibit Behaviors Consistent with Psychotic Disorders
Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, and several intronic single nucleotide polymorphisms in NRG3 are associated with delusions in patients with schizophrenia. In order to gain insights into the biological function of the gene, we generated a novel Nrg3 knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired prepulse inhibition of the acoustic startle response, and deficient fear condi...
Source: Molecular Neuropsychiatry - May 19, 2016 Category: Neuroscience Source Type: research
Genetics of Common Antipsychotic-Induced Adverse Effects
The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria p...
Source: Molecular Neuropsychiatry - May 19, 2016 Category: Neuroscience Source Type: research
Erratum
Mol Neuropsychiatry 2016;2:60 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - May 17, 2016 Category: Neuroscience Source Type: research
Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo 15N metabolic labeling combined with mass...
Source: Molecular Neuropsychiatry - April 29, 2016 Category: Neuroscience Source Type: research
A Review of Genome-Wide Association Studies of Stimulant and Opioid Use Disorders
Substance use disorders (SUD) are a major contributor to disability and disease burden worldwide. Risk for developing SUDs is influenced by variation in the genome. Identifying the genetic variants that influence SUD risk may help us to understand the biological mechanisms for the disorders and improve treatments. Genome-wide association studies (GWAS) have been successful in identifying many regions of the genome associated with common human disorders. Here, findings from recent GWAS of SUDs that involve illicit substances will be reviewed. Several GWAS have been reported, including studies on opioid and stimulant use dis...
Source: Molecular Neuropsychiatry - April 12, 2016 Category: Neuroscience Source Type: research
Cell Type-Specific Effects of Mutant DISC1: A Proteomics Study
Despite the recent progress in psychiatric genetics, very few studies have focused on genetic risk factors in glial cells that, compared to neurons, can manifest different molecular pathologies underlying psychiatric disorders. In order to address this issue, we studied the effects of mutant disrupted in schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured primary neurons and astrocytes using an unbiased mass spectrometry-based proteomic approach. We found that selective expression of mutant DISC1 in neurons affects a wide variety of proteins predominantly involved in neuronal development (e.g., SO...
Source: Molecular Neuropsychiatry - March 31, 2016 Category: Neuroscience Source Type: research
SUMOylation of DISC1: A Potential Role in Neural Progenitor Proliferation in the Developing Cortex
In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex.Mol Neuropsychiatry 2016;2:20-27 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - March 15, 2016 Category: Neuroscience Source Type: research
Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications
This article reviews the evidence implicating inflammatory cytokines in AIWG and its potential clinical relevance.Mol Neuropsychiatry 2016;2:1-14 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - January 13, 2016 Category: Neuroscience Source Type: research
A Case for Returning to Multiplex Families for Further Understanding the Heritability of Schizophrenia: A Psychiatrist's Perspective
The genetic mechanism for schizophrenia still remains unknown despite decades of research. A tremendous amount of investigator time and effort has gone into ascertainment of clinical samples for genetic studies over the years. Most recently, a large international effort of unprecedented collaboration has occurred to combine data worldwide in pursuit of uncovering the relevant genetic risk factors. However, in the process, the use of multiplex families to understand the genetics has waned, and it has been presumed that large resources of unrelated patients and controls are more efficient to find risk alleles than families. ...
Source: Molecular Neuropsychiatry - January 13, 2016 Category: Neuroscience Source Type: research
Contents Vol. 1, 2015
Mol Neuropsychiatry 2015;1:I-IV (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - December 15, 2015 Category: Neuroscience Source Type: research
Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome
22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF ...
Source: Molecular Neuropsychiatry - December 4, 2015 Category: Neuroscience Source Type: research
