κ-Opioid Receptor Modulation of GABAergic Inputs onto Ventrolateral Periaqueductal Gray Dopamine Neurons
In this study, we sought to determine the impact of KOR signaling on GABAergic inputs o nto vlPAG DA neurons, and the mechanism through which KOR impacts these inputs. We found that activation of KOR reduced GABAergic transmission onto vlPAG DA neurons. In addition, our data suggest this effect is mediated presynaptically via the G protein βγ-subunit. They raise the possibility that KOR activation disinhibits vlPAG DA neurons, which could lead to altered regulation of pain-related behaviors.Mol Neuropsychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - May 17, 2019 Category: Neuroscience Source Type: research
Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review
There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification ofmyo-inositol levels is a putative glial marke...
Source: Molecular Neuropsychiatry - May 9, 2019 Category: Neuroscience Source Type: research
Sex-Specific Effects of Stress on Mood-Related Gene Expression
Women are twice as likely as men to be diagnosed with major depressive disorder (MDD). Recent studies report distinct molecular changes in depressed men and women across mesocorticolimbic brain regions. However, it is unclear which sex-related factors drive distinct MDD-associated pathology. The goal of this study was to use mouse experimental systems to investigate sex-specific mechanisms underlying the distinct molecular profiles of MDD in men and women. We used unpredictable chronic mild stress to induce an elevated anxiety-/depressive-like state and “four core genotypes” (FCG) mice to probe for sex-specific mechani...
Source: Molecular Neuropsychiatry - May 6, 2019 Category: Neuroscience Source Type: research
Entrainment of Circadian Rhythms to Temperature Reveals Amplitude Deficits in Fibroblasts from Patients with Bipolar Disorder and Possible Links to Calcium Channels
Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD.CACNA1C encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is involved in circadian phase delays. It is unknown whether variants inCACNA1C or other calcium channels contribute to the circadian phenotype in BD. We hypothesized that, by using temperature cycles, we could model circadian entrainment in fibroblasts from BD patients and controls to...
Source: Molecular Neuropsychiatry - April 8, 2019 Category: Neuroscience Source Type: research
Electroconvulsive Therapy and Schizophrenia: A Systematic Review
Electroconvulsive therapy (ECT) is a remarkably effective treatment for major depressive disorder, but is less commonly utilized for treatment of psychotic disorders. Recent literature indicates that ECT can be a useful strategy for a wide range of psychotic disorders, including treatment-resistant schizophrenia. The purpose of this review is to examine the extant literature on ECT in schizophrenia with a primary focus on its efficacy, its impact on cognitive function, the role of maintenance ECT, and the potential role of neuroimaging biomarkers to provide more precise ECT treatment strategies. We evaluated the available ...
Source: Molecular Neuropsychiatry - April 4, 2019 Category: Neuroscience Source Type: research
Transcriptional Changes following Cellular Knockdown of the Schizophrenia Risk Gene < b > < i > SETD1A < /i > < /b > Are Enriched for Common Variant Association with the Disorder
Loss of function mutations inSETD1A are the first experiment-wide significant findings to emerge from exome sequencing studies of schizophrenia. AlthoughSETD1A is known to encode a histone methyltransferase, the consequences of reduced SETD1A activity on gene expression in neural cells have, to date, been unknown. To explore transcriptional changes through which genetic perturbation ofSETD1A could confer risk for schizophrenia, we have performed genome-wide gene expression profiling of a commonly used human neuroblastoma cell line in whichSETD1A expression has been experimentally reduced using RNA interference (RNAi). We i...
Source: Molecular Neuropsychiatry - March 31, 2019 Category: Neuroscience Source Type: research
Prelims
Mol Neuropsychiatry 2019;5:1 –4 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - March 15, 2019 Category: Neuroscience Source Type: research
Author / Subject Index
Mol Neuropsychiatry 2019;5:74 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - March 15, 2019 Category: Neuroscience Source Type: research
Complex Neurological Phenotype in Female Carriers of < b > < i > NHE6 < /i > < /b > Mutations
Mutations inNHE6 (also termedSLC9A6) cause the X-linked neurological disorder Christianson syndrome (CS) in males. The purpose of this study was to examine the phenotypic spectrum of female carriers ofNHE6 mutations. Twenty female carriers from 9 pedigrees were enrolled, ranging from approximately age 2 to 65. A subset of female carriers was assessed using standardized neuropsychological measures. Also, the association ofNHE6 expression with markers of brain age was evaluated using 740 participants in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). A majority, but not all, female carriers demonstr...
Source: Molecular Neuropsychiatry - March 7, 2019 Category: Neuroscience Source Type: research
Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches
Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in genomewide screens, suggesting a role for epigenetic effects. Rather, large numbers of weakly acting loci may cumulatively increase disease risk, including several mapping to epigenetic pathways. In this review, we discuss mechan...
Source: Molecular Neuropsychiatry - February 15, 2019 Category: Neuroscience Source Type: research
Contents Vol. 4, 2018
Mol Neuropsychiatry 2018;4:I –IV (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - February 8, 2019 Category: Neuroscience Source Type: research
Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder
Mitochondrial dysfunction has been associated with schizophrenia (SZ) and bipolar disorder (BD). This review examines recent publications and novel associations between mitochondrial genes and SZ and BD. Associations of nuclear-encoded mitochondrial variants with SZ were found using gene- and pathway-based approaches. Two control region mitochondrial DNA (mtDNA) SNPs, T16519C and T195C, both showed an association with SZ and BD. A review of 4 studies of A15218G located in the cytochrome B oxidase gene (CYTB, SZ = 11,311, control = 35,735) shows a moderate association with SZ (p = 2.15E-03). Another mtDNA allele A12308G was...
Source: Molecular Neuropsychiatry - February 5, 2019 Category: Neuroscience Source Type: research
Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview
Neuropsychiatric and neurologic diseases cause a great burden for individuals, families, and societies. Social isolation rearing can trigger a variety of psychiatric diseases. New advances suggest that epigenetic factors along with other neurochemical changes can be an important topic in neuropsychiatric diseases. It is thought that the prevention of social isolation rearing that occurs around birth can reduce the occurrence of neuropsychiatric diseases. It has been suggested that the environment can induce epigenetic alternation. So, for the diagnosis of a proportion of neuropsychiatric diseases, assessing epigenetic fact...
Source: Molecular Neuropsychiatry - January 27, 2019 Category: Neuroscience Source Type: research
Cell Type-Specific Gene Expression of Alpha 5 Subunit-Containing Gamma-Aminobutyric Acid Subtype A Receptors in Human and Mouse Frontal Cortex
In this study, multilabel fluorescence in situ hybridization was used to characterize α5-GABAAR gene expression in PYCs and three GABAergic neuron subgroups – vasoactive intestinal peptide (VIP)-, SST-, and parvalbumin (PV)-expressing cells – in the human and mouse frontal cortex. Across species, we found the majority of gene expression in PYCs (human: 39.7%; mouse: 54.14%), less abundant expression in PV neurons (human: 20%; mouse: 16.33%), and no expression in VIP neurons (0%). Only human SST cells expressed GABRA5, albeit at low levels (human: 8.3%; mouse: 0%). Together, this localization suggests potential roles f...
Source: Molecular Neuropsychiatry - January 23, 2019 Category: Neuroscience Source Type: research
Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles
Altered gamma-aminobutyric acid (GABA) function is consistently reported in psychiatric disorders, normal aging, and neurodegenerative disorders and reduced function of GABA interneurons is associated with both mood and cognitive symptoms. Benzodiazepines (BZ) have broad anxiolytic, but also sedative, anticonvulsant and amnesic effects, due to nonspecific GABA-A receptor (GABAA-R) targeting. Varying the profile of activity of BZs at GABAA-Rs is predicted to uncover additional therapeutic potential. We synthesized four novel imidazobenzodiazepine (IBZD) amide ligands and tested them for positive allosteric modulation at mul...
Source: Molecular Neuropsychiatry - January 23, 2019 Category: Neuroscience Source Type: research
