Disordered Ripples Are a Common Feature of Genetically Distinct Mouse Models Relevant to Schizophrenia
We present results from a novel comparative approach to the study of the mechanisms of psychiatric disease. Previous work has examined neural activity patterns in the hippocampus of a freely behaving mouse model associated with schizophrenia, the calcineurin knockout mouse. Here, we examined a genetically distinct mouse model that exhibits a similar set of behavioral phenotypes associated with schizophrenia, a transgenic model expressing a putative dominant-negative DISC1 (DN-DISC1). Strikingly, the principal finding of the earlier work is replicated in the DN-DISC1 mice, that is, a selective increase in the numbers of sha...
Source: Molecular Neuropsychiatry - April 26, 2015 Category: Neuroscience Source Type: research
Sigma-1 and N-Methyl-D-Aspartate Receptors: A Partnership with Beneficial Outcomes
Sigma-1 receptors (σ-1R) are interorganelle signaling molecules, which have been implicated in synaptic plasticity, primarily by enhancing the function of N-methyl-D-aspartate receptors (NMDARs). On the other hand, excessive influx of calcium via activated NMDAR can cause excitotoxicity. Yet, despite their NMDAR-enhancing role, multiple lines of evidence suggest that σ-1Rs are involved in neuroprotection. The mechanism underlying these intriguing opposing effects is not known. Recent studies now suggest the possibility that σ-1Rs could exert neuroprotective effects via targeted disruption of protein-protein interactions...
Source: Molecular Neuropsychiatry - March 10, 2015 Category: Neuroscience Source Type: research
Identification and Functional Studies of Regulatory Variants Responsible for the Association of NRG3 with a Delusion Phenotype in Schizophrenia
We previously reported a genetic linkage for schizophrenia (SZ; nonparametric linkage score of 4.27) at 10q22 in an Ashkenazi Jewish (AJ) population. In follow-up fine-mapping, we found strong evidence for an association between 3 intronic single nucleotide variants (SNVs) in the 5′ end of neuregulin 3 (NRG3) and the delusion factor score of our phenotypic principal component analysis. Two independent groups replicated these findings, indicating that variants in NRG3 confer a risk for a delusion-rich SZ subtype. To identify the causative variants, we sequenced the 162-kb linkage disequilibrium block covering the NRG3 5â€...
Source: Molecular Neuropsychiatry - February 27, 2015 Category: Neuroscience Source Type: research
Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains
Recent advances in genome-wide association studies are pointing towards a major role for voltage-gated ion channels in neuropsychiatric disorders and, in particular, bipolar disorder (BD). The phenotype of BD is complex, with symptoms during mood episodes and deficits persisting between episodes. We have tried to elucidate the common neurobiological mechanisms associated with ion channel signaling in order to provide a new perspective on the clinical symptoms and possible endophenotypes seen in BD patients. We propose a model in which the multiple variants in genes coding for ion channel proteins would perturb motivational...
Source: Molecular Neuropsychiatry - February 19, 2015 Category: Neuroscience Source Type: research
Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion among Clinically High-Risk Youth Developing Psychotic Disorders
In this report, we investigated whether symptom severity as measured by the Scale of Prodromal Symptoms (SOPS) predicted the accelerated gray matter decline in 274 CHR cases, including 35 who converted to psychosis. Higher levels of unusual thought content at baseline were associated with a steeper rate of gray matter loss in the prefrontal cortex bilaterally among converters. In contrast, there was no association found among nonconverters. Steeper gray matter loss seems to be unique to those (CHR) individuals with higher levels of subpsychotic predelusional symptoms that acutely worsen in the ramp-up to full-blown psychos...
Source: Molecular Neuropsychiatry - February 13, 2015 Category: Neuroscience Source Type: research
Molecular and Genetic Characterization of Depression: Overlap with Other Psychiatric Disorders and Aging
Genome-wide expression and genotyping technologies have uncovered the genetic bases of complex diseases at unprecedented rates. However, despite its heavy burden and high prevalence, the molecular characterization of major depressive disorder (MDD) has lagged behind. Transcriptome studies report multiple brain disturbances but are limited by small sample sizes. Genome-wide association studies (GWAS) report weak results but suggest an overlapping genetic risk with other neuropsychiatric disorders. We performed a systematic molecular characterization of altered brain function in MDD using meta-analysis of differential expres...
Source: Molecular Neuropsychiatry - January 8, 2015 Category: Neuroscience Source Type: research
