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Molecular Neuropsychiatry

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https://www.readbyqxmd.com/read/29595840/erratum
#1
(no author information available yet)
[This corrects the article DOI: 10.1159/000480349.].
February 2018: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29594136/crossing-the-worm-brain-barrier-by-using-caenorhabditis-elegans-to-explore-fundamentals-of-human-psychiatric-illness
#2
REVIEW
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
https://www.readbyqxmd.com/read/29594135/mitochondrial-complex-i-deficiency-in-schizophrenia-and-bipolar-disorder-and-medication-influence
#3
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
https://www.readbyqxmd.com/read/29594134/the-comt-val158met-polymorphism-and-exploratory-behavior-in-bipolar-mania
#4
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
https://www.readbyqxmd.com/read/29594133/improved-scalability-of-neuron-based-phenotypic-screening-assays-for-therapeutic-discovery-in-neuropsychiatric-disorders
#5
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
https://www.readbyqxmd.com/read/29594132/interleukin-17-alteration-in-first-episode-psychosis-a-meta-analysis
#6
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
https://www.readbyqxmd.com/read/29594131/a-genome-wide-search-for-bipolar-disorder-risk-loci-modified-by-mitochondrial-genome-variation
#7
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
https://www.readbyqxmd.com/read/29230399/role-of-protein-kinase-c-in-bipolar-disorder-a-review-of-the-current-literature
#8
REVIEW
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
https://www.readbyqxmd.com/read/29230398/insulin-signaling-deficiency-produces-immobility-in-caenorhabditis-elegans-that-models-diminished-motivation-states-in-man-and-responds-to-antidepressants
#9
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
https://www.readbyqxmd.com/read/29230397/circuitry-based-human-neuroanatomy-for-the-next-generation-in-psychiatry-and-neuroscience
#10
Takeshi Sakurai
No abstract text is available yet for this article.
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29230396/altered-expression-of-endoplasmic-reticulum-stress-related-genes-in-the-middle-frontal-cortex-of-subjects-with-autism-spectrum-disorder
#11
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
https://www.readbyqxmd.com/read/29230395/thc-treatment-alters-glutamate-receptor-gene-expression-in-human-stem-cell-derived-neurons
#12
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
https://www.readbyqxmd.com/read/28879201/wnt-%C3%AE-catenin-pathway-and-epigenetic-mechanisms-regulate-the-pitt-hopkins-syndrome-and-schizophrenia-risk-gene-tcf4
#13
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
https://www.readbyqxmd.com/read/28879200/the-nuclear-proteome-of-white-and-gray-matter-from-schizophrenia-postmortem-brains
#14
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
https://www.readbyqxmd.com/read/28879199/low-density-neuronal-cultures-from-human-induced-pluripotent-stem-cells
#15
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
https://www.readbyqxmd.com/read/28879198/complement-c3-expression-is-decreased-in-autism-spectrum-disorder-subjects-and-contributes-to-behavioral-deficits-in-rodents
#16
Kiley Fagan, Amanda Crider, Anthony O Ahmed, Anilkumar Pillai
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 in the middle frontal gyrus of ASD subjects compared to controls...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879197/a-preliminary-study-of-the-opioid-system-and-personality-traits-using-positron-emission-tomography
#17
Alexandra M Rodman, Thilo Deckersbach, Tina Chou, Jian Kong, Randy L Gollub, Darin D Dougherty
BACKGROUND: Personality traits, such as Neuroticism and Extraversion, have been implicated in the processing of emotion. The neural correlates most often associated with Neuroticism and Extraversion are the insular cortex, orbitofrontal cortex, amygdala, and ventral striatum. OBJECTIVE: The aim of the current study was to explore neurotransmitter systems underlying those neural correlates and investigate the relationship between personality traits and opioid receptor binding potential...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879196/assessment-of-whole-exome-sequence-data-in-attempted-suicide-within-a-bipolar-disorder-cohort
#18
Eric T Monson, Mehdi Pirooznia, Jennifer Parla, Melissa Kramer, Fernando S Goes, Marie E Gaine, Sophia C Gaynor, Kelly de Klerk, Dubravka Jancic, Rachel Karchin, W Richard McCombie, Peter P Zandi, James B Potash, Virginia L Willour
Suicidal behavior is a complex and devastating phenotype with a heritable component that has not been fully explained by existing common genetic variant analyses. This study represents the first large-scale DNA sequencing project designed to assess the role of rare functional genetic variation in suicidal behavior risk. To accomplish this, whole-exome sequencing data for ∼19,000 genes were generated for 387 bipolar disorder subjects with a history of suicide attempt and 631 bipolar disorder subjects with no prior suicide attempts...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277568/neurodevelopmental-perspectives-on-wnt-signaling-in-psychiatry
#19
REVIEW
Kimberly A Mulligan, Benjamin N R Cheyette
Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277567/evidence-of-as3mt-d2d3-associated-variants-within-10q24-32-33-in-the-genetic-risk-of-major-affective-disorders
#20
Lingyi Li, Hong Chang, Tao Peng, Ming Li, Xiao Xiao
Genome-wide association studies suggest that 10q24.32-33 is a risk region for schizophrenia (SCZ). Considering the substantial genetic overlap between SCZ and major affective disorders, we would like to investigate whether the 10q24.32-33 region confers risk of affective disorders. We chose three SCZ genome-wide significant SNPs (rs7914558, rs7085104, and rs11191580) in 10q24.32-33 and collected the statistical data from European and Asian populations to perform systematic meta-analyses, which finally included up to 26,413 cases with affective disorders and 24,849 controls...
February 2017: Molecular Neuropsychiatry
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