Nuclear Receptors and Neuroinflammation in Schizophrenia
Conclusion: In schizophrenia, changes in nuclear receptor mRNA levels involved with mediating actions of vitamin A derivatives vary according to the inflammatory state of brains.Mol Neuropsychiatry 2017;3:181 –191 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - January 16, 2018 Category: Neuroscience Source Type: research
Erratum
Mol Neuropsychiatry 2017;3:180 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - January 11, 2018 Category: Neuroscience Source Type: research
Crossing the Worm-Brain Barrier by Using < b > < i > Caenorhabditis elegans < /i > < /b > to Explore Fundamentals of Human Psychiatric Illness
Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to deconvolute psychiatric illnesses into fundamental symptom clusters or biological markers more closely linked to genetic influences. By taking this one step farther, these biomarkers can be reduced to protophenotypes - endophenotypes conserved during evolution - with counterparts in lower organisms includingCaenorhabditis elegans andDrosophila. Striking conservation inC. elegans of genes that increase the risk for mental illness bolsters the relevance of this model system for psychiatric research. Here, I review the characterization of several p...
Source: Molecular Neuropsychiatry - January 10, 2018 Category: Neuroscience Source Type: research
Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence
Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA “common deletion” in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls (p = 0.02), while no significant difference was found in BD. Complex I activity was significantly decreased (p = 0....
Source: Molecular Neuropsychiatry - November 29, 2017 Category: Neuroscience Source Type: research
The COMT Val158Met Polymorphism and Exploratory Behavior in Bipolar Mania
Conclusion: This preliminary study suggests that arousal and positive valence are influenced in a linear fashion by COMT, presumably due to increased catecholamine in frontal regions, but these findings require replication in a larger sample. The hBPM can enable cross-species and transdiagnostic studies to inform neurobiology of psychiatric disorders.Mol Neuropsychiatry 2017;3:151-156 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - November 21, 2017 Category: Neuroscience Source Type: research
Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic Discovery in Neuropsychiatric Disorders
There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such as neuronal connectivity, exhibit poor scalability and are not compatible with high-throughput screening (HTS) procedures. Therefore, we created a neuronal phenotypic assay platform that focused on improving the scalability and affordability of neuron-based assays capable of trac...
Source: Molecular Neuropsychiatry - November 16, 2017 Category: Neuroscience Source Type: research
Insulin Signaling Deficiency Produces Immobility in < b > < i > Caenorhabditis elegans < /i > < /b > That Models Diminished Motivation States in Man and Responds to Antidepressants
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes inCaenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail ...
Source: Molecular Neuropsychiatry - November 2, 2017 Category: Neuroscience Source Type: research
Interleukin-17 Alteration in First-Episode Psychosis: A Meta-Analysis
Schizophrenia is accompanied with central nervous system and peripheral immune system imbalances. Interleukin-17 (IL-17) is implicated in various immune and inflammatory processes. Aberrant levels of IL-17 have been reported in patients with schizophrenia, whereas the results are not consistent. To clarify the relationship between IL-17 and schizophrenia, we performed a meta-analysis in this study. We carried out a structured literature search in PubMed and Embase database up to April 16, 2017, and retrieved all eligible case-control studies according to the inclusion criteria. Finally, a total of 313 patients with drug-na...
Source: Molecular Neuropsychiatry - October 27, 2017 Category: Neuroscience Source Type: research
A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation
In this study, we performed genome-wide analyses to assess mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early-onset BD (EOBD) among BD patients, focusing on interaction effects between nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European American BD cases (n = 1,001) and controls (n = 1,034) from the Genetic Association Information Network BD study were analyzed to assess the joint effect of nSNP and nSNP-mtSNP interaction on the risk of BD and EOBD. The effect of nSNP-mtSNP interactions was also assessed. For BD risk, the strongest evidence of an association was obtained...
Source: Molecular Neuropsychiatry - October 27, 2017 Category: Neuroscience Source Type: research
A Preliminary Study of the Opioid System and Personality Traits Using Positron Emission Tomography
Conclusions: While preliminary, the results of this study suggest that the expression of Neuroticism and Extraversion is related to baseline function of the opioid neurotransmitter system in the insular cortex. These findings may help elucidate the neural mechanisms underlying the expression of personality traits, particularly those implicated in affective processing.Mol Neuropsychiatry 2017;3:12-18 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels ...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
The Nuclear Proteome of White and Gray Matter from Schizophrenia Postmortem Brains
Schizophrenia (SCZ) is a serious neuropsychiatric disorder that manifests through several symptoms from early adulthood. Numerous studies over the last decades have led to significant advances in increasing our understanding of the factors involved in SCZ. For example, mass spectrometry-based proteomic analysis has provided important insights by uncovering protein dysfunctions inherent to SCZ. Here, we present a comprehensive analysis of the nuclear proteome of postmortem brain tissues from corpus callosum (CC) and anterior temporal lobe (ATL). We show an overview of the role of deregulated nuclear proteins in these two ma...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Low-Density Neuronal Cultures from Human Induced Pluripotent Stem Cells
We describe a differentiation protocol to generate low-density neuronal cultures ( ∼2,500 neurons/cm2) from human iPSC-derived neural stem cells/early neural progenitor cells. We generated low-density cultures using cells from 3 individuals. We also evaluated the morphometric features of neurons derived from 2 of these individuals, one harboring a microdeletion on chromosome 15q11.2 and the other without the microdeletion. An approximately 7.5-fold increase in the density of dendritic filopodia was observed in the neurons with the microdeletion, consistent with previous reports. Low-density neuronal cultures enable facil...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
WNT/ β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene TCF4
Genetic variation within the transcription factorTCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood. Here, we quantitated multiple distinctTCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts. We identify two classes of pharmacological tr...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder
The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress. However, it is not known whether ER stress-related genes are altered in the brain of ASD subjects. In the present study, we investigated the mRNA expression of ER stress-related genes (ATF4, ATF6,...
Source: Molecular Neuropsychiatry - October 25, 2017 Category: Neuroscience Source Type: research
