Epigenetic Age in Male Combat-Exposed War Veterans: Associations with Posttraumatic Stress Disorder Status
In conclusion, veterans with PTSD had significantly lower epigenetic age profiles than those without PTSD. Further, current antidepressant use and higher telomerase activity were related to relatively less epigenetic aging in veterans with PTSD, speculative of a mechanistic pathway that might attenuate biological aging-related processes in the context of PTSD.Mol Neuropsychiatry 2018;4:102 –111 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - September 7, 2018 Category: Neuroscience Source Type: research
The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review
The X chromosome has long been an intriguing site for harboring genes that have importance in brain development and function. It has received the most attention for having specific genes underlying the X-linked inherited intellectual disabilities, but has also been associated with schizophrenia in a number of early studies. An X chromosome hypothesis for a genetic predisposition for schizophrenia initially came from the X chromosome anomaly population data showing an excess of schizophrenia in Klinefelter ’s (XXY) males and triple X (XXX) females. Crow and colleagues later expanded the X chromosome hypothesis to include ...
Source: Molecular Neuropsychiatry - August 20, 2018 Category: Neuroscience Source Type: research
Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder
Conclusions: This finding may imply greater organization of the CAB with increasing PTSD severity. The CAB connects directly to the cingulate cortex and the hippocampal subiculum, critical nodes of the default mode network, as well as being implicated in neurodegeneration pathology, decision-making, and executive functions, which may help explain previously shown alterations in this network in PTSD.Message of the Paper: Further study of white matter tract integrity in PTSD is warranted, particularly to investigate whether the CAB connections with both higher-order cognitive functioning and emotion processing regions contri...
Source: Molecular Neuropsychiatry - July 19, 2018 Category: Neuroscience Source Type: research
Attenuated Mismatch Negativity in Attenuated Psychosis Syndrome Predicts Psychosis: Can Galantamine-Memantine Combination Prevent Psychosis?
Although first proposed in 1987, early diagnosis and intervention of psychotic disorders has only recently become a priority in the field. The interest in clinical high risk (CHR) for psychosis skyrocketed after attenuated psychosis syndrome (APS) was added to the DSM-5. There is evidence that in individuals with APS, attenuated mismatch negativity (MMN: functioning of the auditory sensory memory system) is a robust biomarker that can predict transition to psychosis. The underlying pathophysiological mechanism of MMN is via the interaction ofN-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine ( α-7nACh) recept...
Source: Molecular Neuropsychiatry - June 7, 2018 Category: Neuroscience Source Type: research
Recent Advances in the Genetics of Schizophrenia
The last decade brought tremendous progress in the field of schizophrenia genetics. As a result of extensive collaborations and multiple technological advances, we now recognize many types of genetic variants that increase the risk. These include large copy number variants, rare coding inherited and de nov ο variants, and over 100 loci harboring common risk variants. While the type and contribution to the risk vary among genetic variants, there is concordance in the functions of genes they implicate, such as those whose RNA binds the fragile X-related protein FMRP and members of the activity-regulated cytoskeletal complex...
Source: Molecular Neuropsychiatry - May 30, 2018 Category: Neuroscience Source Type: research
The Complex Interaction of Mitochondrial Genetics and Mitochondrial Pathways in Psychiatric Disease
While accounting for only 2% of the body ’s weight, the brain utilizes up to 20% of the body’s total energy. Not surprisingly, metabolic dysfunction and energy supply-and-demand mismatch have been implicated in a variety of neurological and psychiatric disorders. Mitochondria are responsible for providing the brain with most of its ene rgetic demands, and the brain uses glucose as its exclusive energy source. Exploring the role of mitochondrial dysfunction in the etiology of psychiatric disease is a promising avenue to investigate further. Genetic analysis of mitochondrial activity is a cornerstone in understanding dis...
Source: Molecular Neuropsychiatry - May 30, 2018 Category: Neuroscience Source Type: research
Contents Vol. 3, 2017
Mol Neuropsychiatry 2017;3:I –IV (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - May 17, 2018 Category: Neuroscience Source Type: research
Further Evidence of an Association between < b > < i > NCAN < /i > < /b > rs1064395 and Bipolar Disorder
Genome-wide association studies suggest that rs1064395 in the neurocan gene (NCAN) is a potential risk factor for bipolar disorder (BPD), and further replication analyses in larger independent samples are needed. We herein analyzed rs1064395 in a Han Chinese sample of 1,146 BPD cases and 2,031 controls, followed by a meta-analysis of BPD samples from worldwide populations including a total of 15,318 cases and 91,990 controls. The meta-analysis found that rs1064395 showed a genome-wide significant association with BPD (p = 4.92 × 10–9, OR = 1.126 for the A allele), although it did not reach the significance level in the ...
Source: Molecular Neuropsychiatry - May 17, 2018 Category: Neuroscience Source Type: research
Dominant-Negative DISC1 Alters the Dopaminergic Modulation of Inhibitory Interneurons in the Mouse Prefrontal Cortex
A truncateddisrupted in schizophrenia 1 (Disc1) gene increases the risk of psychiatric disorders, probably affecting cortical interneurons. Here, we sought to determine whether this cell population is affected in mice carrying a truncated (Disc1) allele (DN-DISC1). We utilized whole cell recordings to assess electrophysiological properties and modulation by dopamine (DA) in two classes of interneurons: fast-spiking (FS) and low threshold-spiking (LTS) interneurons in wild-type and DN-DISC1 mice. In DN-DISC1 mice, FS interneurons, but not LTS interneurons, exhibited altered action potentials. Further, the perineuronal nets ...
Source: Molecular Neuropsychiatry - May 7, 2018 Category: Neuroscience Source Type: research
Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients
Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.Mol Neuropsychiatry 2018;4:1 –6 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - May 3, 2018 Category: Neuroscience Source Type: research
Association of Novel ALX4 Gene Polymorphisms with Antidepressant Treatment Response: Findings from the CO-MED Trial
Genome-wide association studies (GWAS) were conducted in participants of the CO-MED (Combining Medications to Enhance Depression Outcomes) trial, a randomized, 3-treatment arm clinical trial of major depressive disorder (MDD) designed to identify markers of differential treatment outcome (response and remission). The QIDS-SR (Quick Inventory of Depressive Symptomatology, Self-Reported version) was used to measure response at week 6 (QIDS-SR ≤5) and remission at week 12 (QIDS-SR ≤6 and ≤8 at the last two study visits). Three treatment groups (escitalopram monotherapy, escitalopram + bupropion, and venlafaxine + mirtaz...
Source: Molecular Neuropsychiatry - May 3, 2018 Category: Neuroscience Source Type: research
Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in < b > < i > Fez1 < /i > < /b > -Deficient Mice
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that, while prevalent, has a stagnant track record for advances in treatment. The limited availability of animal models with appropriate face and predictive validities has hampered progress in developing novel neurobiological hypotheses and testing new therapeutic options for this condition. Here, we report that mice deficient inFez1, a gene specifically expressed in the nervous system with documented functions in neurodevelopment, show hyperactivity and impulsivity phenotypes, which are ameliorated by administering methylphenidate (MPH) or gu...
Source: Molecular Neuropsychiatry - April 26, 2018 Category: Neuroscience Source Type: research
Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study
Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole b...
Source: Molecular Neuropsychiatry - April 17, 2018 Category: Neuroscience Source Type: research
Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder
This study developed potential blood-based biomarker tests for diagnosing and differentiating schizophrenia (SZ), bipolar disorder type I (BD), and normal control (NC) subjects using mRNA gene expression signatures. A total of 90 subjects (n = 30 each for the three groups of subjects) provided blood samples at two visits. The Affymetrix exon microarray was used to profile the expression of over 1.4 million probesets. We selected potential biomarker panels using the temporal stability of the probesets and also back-tested them at two different visits for each subject. The 18-gene biomarker panels, using logistic regression ...
Source: Molecular Neuropsychiatry - April 10, 2018 Category: Neuroscience Source Type: research
Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls
The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence. Forty euthymic patients with BD type I, aged 18 –65 years, were included in this study. The healthy comparison group consisted of 39 volunteers who had no current or lifetime history of mental disorders, no use of psychotropic medications, and no known family history of mood disorders or psychosis. Peripheral blood mononuclear cells from BD pat ients and healthy controls were collected and isolated. The cells were allowed to grow in culture and stimulated for 3 days. CD69 was m...
Source: Molecular Neuropsychiatry - February 1, 2018 Category: Neuroscience Source Type: research
