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Molecular Neuropsychiatry

Akiko Sumitomo, Ayumi Saka, Keisho Ueta, Kouta Horike, Kazuko Hirai, Nao J Gamo, Takatoshi Hikida, Keiichi I Nakayama, Akira Sawa, Takeshi Sakurai, Toshifumi Tomoda
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 in Fez1 , 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 guanfacine (GFC), two pharmacological agents used for ADHD treatment...
May 2018: Molecular Neuropsychiatry
Thomas W Sedlak, Leslie G Nucifora, Minori Koga, Lindsay S Shaffer, Cecilia Higgs, Teppei Tanaka, Anna M Wang, Jennifer M Coughlin, Peter B Barker, Jed W Fahey, Akira Sawa
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...
May 2018: Molecular Neuropsychiatry
Marquis Philip Vawter, Robert Philibert, Brandi Rollins, Patricia L Ruppel, Terry W Osborn
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...
May 2018: Molecular Neuropsychiatry
Ana S Yamagata, Lucas B Rizzo, Raphael O Cerqueira, Janine Scott, Quirino Cordeiro, Roger S McIntyre, Rodrigo B Mansur, Elisa Brietzke
Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. 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...
May 2018: Molecular Neuropsychiatry
Shan-Yuan Tsai, Vibeke S Catts, Janice M Fullerton, Susan M Corley, Stuart G Fillman, Cynthia Shannon Weickert
Introduction: Several nuclear receptor family members have been associated with schizophrenia and inflammation. Vitamins A and D exert anti-inflammatory actions, but their receptors (mainly nuclear receptors) have not been extensively studied in either schizophrenia brains or in association with neuroinflammation. We examined the expression of vitamin A (RARs and RXRs) and vitamin D and protein disulphide-isomerase A3 (PDIA3) receptors, as well as nuclear orphan receptors (NR4As), in the context of elevated cytokine expression in the dorsolateral prefrontal cortex (DLPFC)...
May 2018: Molecular Neuropsychiatry
(no author information available yet)
[This corrects the article DOI: 10.1159/000480349.].
February 2018: Molecular Neuropsychiatry
Donard S Dwyer
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 including Caenorhabditis elegans and Drosophila . Striking conservation in C. elegans of genes that increase the risk for mental illness bolsters the relevance of this model system for psychiatric research...
February 2018: Molecular Neuropsychiatry
Brandi L Rollins, Ling Morgan, Brooke E Hjelm, Adolfo Sequeira, Alan F Schatzberg, Jack D Barchas, Francis S Lee, Rick M Myers, Stanley J Watson, Huda Akil, Steven G Potkin, William E Bunney, Marquis P Vawter
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...
February 2018: Molecular Neuropsychiatry
Arpi Minassian, Jared W Young, Mark A Geyer, John R Kelsoe, William Perry
Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences cognition and behavior in psychiatric illnesses; its low-activity allele, methionine (Met), may be associated with behavior reflecting catecholamine overactivity. Heightened motor activity and increased positive valence are central features of bipolar disorder (BD) and have been quantified in the human Behavioral Pattern Monitor (hBPM), an exploration paradigm based upon the rodent open field. We examined whether hBPM behavior was related to the COMT gene in a small sample of manic BD patients...
February 2018: Molecular Neuropsychiatry
Timothy P Spicer, Christopher Hubbs, Thomas Vaissiere, Deanna Collia, Camilo Rojas, Murat Kilinc, Kyle Vick, Franck Madoux, Pierre Baillargeon, Justin Shumate, Kirill A Martemyanov, Damon T Page, Sathya Puthanveettil, Peter Hodder, Ronald Davis, Courtney A Miller, Louis Scampavia, Gavin Rumbaugh
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 tracking disease-relevant phenotypes...
February 2018: Molecular Neuropsychiatry
Xinyu Fang, Yi Zhang, Weixing Fan, Wei Tang, Chen Zhang
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...
February 2018: Molecular Neuropsychiatry
Euijung Ryu, Malik Nassan, Gregory D Jenkins, Sebastian M Armasu, Ana Andreazza, Susan L McElroy, Marquis P Vawter, Mark A Frye, Joanna M Biernacka
Mitochondrial DNA mutations have been reported to be associated with bipolar disorder (BD). 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...
February 2018: Molecular Neuropsychiatry
Ashwini Saxena, Giselli Scaini, Daniela V Bavaresco, Camila Leite, Samira S Valvassoria, André F Carvalho, João Quevedo
Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC...
November 2017: Molecular Neuropsychiatry
Julie Dagenhardt, Angeline Trinh, Halen Sumner, Jeffrey Scott, Eric Aamodt, Donard S Dwyer
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 in Caenorhabditis elegans , brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults...
November 2017: Molecular Neuropsychiatry
Takeshi Sakurai
No abstract text is available yet for this article.
November 2017: Molecular Neuropsychiatry
Amanda Crider, Anthony O Ahmed, Anilkumar Pillai
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...
November 2017: Molecular Neuropsychiatry
Ifeanyi V Obiorah, Hamza Muhammad, Khalifa Stafford, Erin K Flaherty, Kristen J Brennand
Given the cognitive and behavioral effects following in utero Δ9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate receptor subunit genes ( GRIA1 , GRIA2, GRIN2A , and GRIN2B ). By expanding these studies across hiPSC-derived neurons from individuals with a variety of genotypes, we believe that a hiPSC-based model will facilitate studies of the interaction of THC exposure and the genetic risk factors underlying neuropsychiatric disease vulnerability...
November 2017: Molecular Neuropsychiatry
Krista M Hennig, Daniel M Fass, Wen-Ning Zhao, Steven D Sheridan, Ting Fu, Serkan Erdin, Alexei Stortchevoi, Diane Lucente, Jannine D Cody, David Sweetser, James F Gusella, Michael E Talkowski, Stephen J Haggarty
Genetic variation within the transcription factor TCF4 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 distinct TCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts...
July 2017: Molecular Neuropsychiatry
Verônica M Saia-Cereda, Aline G Santana, Andrea Schmitt, Peter Falkai, Daniel Martins-de-Souza
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)...
July 2017: Molecular Neuropsychiatry
Peter Dimitrion, Yun Zhi, Dennis Clayton, Gerard L Apodaca, Madeleine R Wilcox, Jon W Johnson, Vishwajit Nimgaonkar, Leonardo D'Aiuto
Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented possibility to investigate defects occurring during neuronal differentiation in neuropsychiatric and neurodevelopmental disorders, but the density and intricacy of intercellular connections in neuronal cultures challenge currently available analytic methods. Low-density neuronal cultures facilitate the morphometric and functional analysis of neurons. We describe a differentiation protocol to generate low-density neuronal cultures (∼2,500 neurons/cm(2)) from human iPSC-derived neural stem cells/early neural progenitor cells...
July 2017: Molecular Neuropsychiatry
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