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 pote...
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

Exercise Reduces Salivary Morning Cortisol Levels in Patients with Depression
Conclusions and Message: PE reduced the rate of cortisol level decline across the day in depressed adults. ICBT and TAU treatments had no detectable effects on diurnal cortisol levels. Larger samples are required for the detection and comparison of smaller effects of PE, ICBT and TAU on diurnal cortisol levels.Mol Neuropsychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - December 19, 2018 Category: Neuroscience Source Type: research

OMICS Approaches to Unravel the Complexity of Psychiatric Disorders: Impact on Biomarker Discovery
Mol Neuropsychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - November 20, 2018 Category: Neuroscience Source Type: research

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse
Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as ...
Source: Molecular Neuropsychiatry - November 20, 2018 Category: Neuroscience Source Type: research

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia
The objective of this article is to critically dissect the published randomized cont rolled trials with galantamine and memantine for CIAS to highlight the efficacy signal. These studies may have failed to detect a clinically meaningful efficacy signal due to limitations, methodological issues, and possible medication nonadherence. There is evidence from a small open-label study tha t the galantamine-memantine combination may be effective for CIAS with kynurenine pathway metabolites as biomarkers to detect the severity of cognitive impairments. Given that there are no available treatments for cognitive impairments and prim...
Source: Molecular Neuropsychiatry - November 20, 2018 Category: Neuroscience Source Type: research

Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia
Lower testosterone levels are associated with greater negative symptoms in men with schizophrenia. Testosterone signals via androgen receptor (AR). A functional variant in the AR gene (CAG trinucleotide repeat polymorphism) is associated with circulating testosterone and mood-related symptoms in healthy people. Raloxifene increases testosterone in healthy males and reduces symptom severity and improves cognition in schizophrenia; however, whether raloxifene increases testosterone in men with schizophrenia is unknown. We assessed the interaction of a functional AR gene variant and adjunctive raloxifene on peripheral testost...
Source: Molecular Neuropsychiatry - November 20, 2018 Category: Neuroscience Source Type: research

Ketamine ’s Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice
In conclusion and in line with previous research, our data indicate that ketamine impacts the AMPAR subunit Gria2 and results in decreased GABAergic inhibitory neurotransmissi on leading to increased excitatory neuronal activity.Mol Neuropsychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - November 15, 2018 Category: Neuroscience Source Type: research

Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder
Conclusion: Interaction between suicide and SUD seems to influence the expression of genes involved in glial proliferation and glutamatergic neurotransmission. These results highlight, for the first time, that suicides with SUD have a gene expression profile distinct from that of subjects with only one of these disorders.Mol Neuropsychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - November 12, 2018 Category: Neuroscience Source Type: research

In the Realm of Psychoneuroimmunology: The Role of Celecoxib as an Add-On Treatment for Bipolar Mania
Bipolar affective disorder (BPAD) is a chronic debilitating psychiatric illness seriously affecting the quality of patients ’ life. The available treatment is effective in about half of those suffering from the illness. The neurobiological basis of the disorder is not fully unraveled. With such lacunae, attempts have been made to decipher the underlying neuroimmunological process of the illness as is the case with othe r mental disorders. As a result, some inflammatory processes have been implicated in the etiology of BPAD, as described in this communication. Subsequently, the role of anti-inflammatory agents such as...
Source: Molecular Neuropsychiatry - November 8, 2018 Category: Neuroscience Source Type: research

Regulation of the Expression of the Psychiatric Risk Gene < b > < i > Cacna1c < /i > < /b > during Associative Learning
CACNA1C encodes the Cav1.2 L-type voltage-gated calcium channel. Generic variation in CACNA1C has been consistently identified as associated with risk for psychiatric disorders including schizophrenia, bipolar disorder, major depressive disorder and autism. Psychiatric risk loci are also enriched for genes involved in the regulation of synaptic plasticity. Here, we show that the expression ofCacna1c is regulated in the rat hippocampus after context exposure, contextual fear conditioning and fear memory retrieval in a manner that correlates to specific memory processes. Using quantitative in situ hybridisation, the expressi...
Source: Molecular Neuropsychiatry - November 7, 2018 Category: Neuroscience Source Type: research

< b > < i > VRK2 < /i > < /b > , a Candidate Gene for Psychiatric and Neurological Disorders
Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 (VRK2) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 inVRK2 showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls,p = 3....
Source: Molecular Neuropsychiatry - November 7, 2018 Category: Neuroscience Source Type: research

Research Domain Criteria: Cutting Edge Neuroscience or Galen ’s Humors Revisited?
The Research Domain Criteria (RDoC) scheme has guided the research agenda of the National Institute of Mental Health for the past decade. The essence of RDoC is its dimensional conception of mental illness, with the assumption that psychopathology is a manifestation of extremes along axes of neuropsychological variation. Research, it follows, should emphasize normal neuropsychological function and its associated neurocircuitry. We argue that RDoC, dressed in terms of modern neurobiology, is in fact a return to the humoral theory of Galen, a dimensional approach in which physical and mental health requires a balance of the ...
Source: Molecular Neuropsychiatry - October 11, 2018 Category: Neuroscience Source Type: research

X-Aptamer Technology Identifies C4A and ApoB in Blood as Potential Markers for Schizophrenia
The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech ­nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients (n = 60) compared to controls (n = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that...
Source: Molecular Neuropsychiatry - October 10, 2018 Category: Neuroscience Source Type: research

Associations between the < b > < i > LEP < /i > < /b > -2548G/A Promoter and Baseline Weight and between < b > < i > LEPR < /i > < /b > Gln223Arg and Lys656Asn Variants and Change in BMI < b > < i > z < /i > < /b > Scores in Arab Children and Adolescents Treated with Risperidone
Data on baseline (antipsychotics-na ïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5–323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17–17.7) attending a pediatric neurology clinic in Saudi Ara bia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardizedz scores (BMIz) were calculated (LMSgrowth program). Linear regression was performed for b...
Source: Molecular Neuropsychiatry - October 5, 2018 Category: Neuroscience Source Type: research

Pharmacogenetics of Antipsychotic Drug Treatment: Update and Clinical Implications
Numerous genetic variants have been shown to be associated with antipsychotic response and adverse effects of schizophrenia treatment. However, the clinical application of these findings is limited. The aim of this narrative review is to summarize the most recent publications and recommendations related to the genetics of antipsychotic treatment and shed light on the clinical utility of pharmacogenetics/pharmacogenomics (PGx). We reviewed the literature on PGx studies with antipsychotic drugs (i.e., antipsychotic response and adverse effects) and commonly used commercial PGx tools for clinical practice. Publications and re...
Source: Molecular Neuropsychiatry - October 4, 2018 Category: Neuroscience Source Type: research

Perturbations of Neuron-Restrictive Silencing Factor Modulate Corticotropin-Releasing Hormone Gene Expression in the Human Cell Line BeWo
Stress exacerbates disease, and understanding its molecular mechanisms is crucial to the development of novel therapeutic interventions to combat stress-related disorders. The driver of the stress response in the hypothalamic-pituitary-adrenal axis (HPA) is corticotropin-releasing hormone (CRH), a neuropeptide synthesized in the paraventricular nucleus of the hypothalamus. Evidence supports that CRH expression is epigenetically modified at the molecular level by environmental stimuli, causing changes in the stress response. This effect is mediated by a concert of factors that translate environmental change into alterations...
Source: Molecular Neuropsychiatry - September 19, 2018 Category: Neuroscience Source Type: research

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 incl...
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) r...
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 ...
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 understan...
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 leve...
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 + mir...
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 w...
Source: Molecular Neuropsychiatry - February 1, 2018 Category: Neuroscience Source Type: research

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

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...
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 fac...
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