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Molecular Neuropsychiatry

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https://www.readbyqxmd.com/read/27867941/familial-influences-on-mismatch-negativity-and-its-association-with-plasma-glutamate-level-a-magnetoencephalographic-study-in-twins
#1
Yukika Nishimura, Yuki Kawakubo, Motomu Suga, Kenji Hashimoto, Yuichi Takei, Kunio Takei, Hideyuki Inoue, Masato Yumoto, Ryu Takizawa, Kiyoto Kasai
Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867940/oxytocin-receptor-oxtr-methylation-and-cognition-in-psychotic-disorders
#2
Tyler B Grove, Kyle J Burghardt, A Zarina Kraal, Ryan J Dougherty, Stephan F Taylor, Vicki L Ellingrod
Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor (OXTR). Within psychotic disorders, it is unknown if OXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral blood OXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101)...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867939/a-rare-variant-in-cacna1d-segregates-with-7-bipolar-i-disorder-cases-in-a-large-pedigree
#3
Jessica Ross, Erika Gedvilaite, Judith A Badner, Carolyn Erdman, Lisa Baird, Nori Matsunami, Mark Leppert, Jinchuan Xing, William Byerley
Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. Within CACNA1D, a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree. A high-resolution DNA denaturing curve method was then used to screen for the presence of the A1751P change in 4,150 BPI cases from the NIMH Genetics Initiative...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867938/a-mutation-in-npas3-that-segregates-with-schizophrenia-in-a-small-family-leads-to-protein-aggregation
#4
Leslie G Nucifora, YeeWen Candace Wu, Brian J Lee, Li Sha, Russell L Margolis, Christopher A Ross, Akira Sawa, Frederick C Nucifora
Schizophrenia and other major mental illnesses result from a complex interplay of genetic and environmental factors. We previously identified a mutation in NPAS3 that results in a valine to isoleucine (V304I) amino acid substitution segregating with schizophrenia in a small family. The amino acid change occurs in a potentially critical region for protein function. Furthermore, the same amino acid substitution in proteins related to familial Alzheimer's disease and transthyretin amyloidosis has been associated with protein aggregation...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867937/dopamine-d2l-receptor-is-required-for-visual-discrimination-and-reversal-learning
#5
Makiko Morita, Yanyan Wang, Toshikuni Sasaoka, Kinya Okada, Minae Niwa, Akira Sawa, Takatoshi Hikida
The corticostriatothalamic circuit regulates learning behaviors via dopamine neurotransmission. D2 long (D2L) receptors are an isoform of dopamine D2 receptors (D2Rs) and may act mainly at postsynaptic sites. It is well known that D2Rs influence high brain functions, but the roles of individual D2R isoforms are still unclear. To assess the influence of D2L receptors in visual discrimination learning, we performed visual discrimination and reversal tasks with D2L knockout mice using a touchscreen operant system...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867936/effects-of-lithium-monotherapy-for-bipolar-disorder-on-gene-expression-in-peripheral-lymphocytes
#6
Amit Anand, Jeanette N McClintick, Jill Murrell, Harish Karne, John I Nurnberger, Howard J Edenberg
BACKGROUND: This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD). METHOD: Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment. Blood RNA samples were collected at baseline and after 2 and 8 weeks of treatment. RNA expression was measured using the Affymetrix GeneChip® Human Gene 1...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606324/the-planar-cell-polarity-transmembrane-protein-vangl2-promotes-dendrite-spine-and-glutamatergic-synapse-formation-in-the-mammalian-forebrain
#7
Nathan D Okerlund, Robert E Stanley, Benjamin N R Cheyette
The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606323/perturbational-profiling-of-metabolites-in-patient-fibroblasts-implicates-%C3%AE-aminoadipate-as-a-potential-biomarker-for-bipolar-disorder
#8
Joanne H Huang, Shaunna S Berkovitch, Jonathan Iaconelli, Bradley Watmuff, Hyoungjun Park, Shrikanta Chattopadhyay, Donna McPhie, Dost Öngür, Bruce M Cohen, Clary B Clish, Rakesh Karmacharya
Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606322/neuregulin-3-knockout-mice-exhibit-behaviors-consistent-with-psychotic-disorders
#9
Lindsay N Hayes, Alexey Shevelkin, Mariela Zeledon, Gary Steel, Pei-Lung Chen, Cassandra Obie, Ann Pulver, Dimitrios Avramopoulos, David Valle, Akira Sawa, Mikhail V Pletnikov
Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, and several intronic single nucleotide polymorphisms in NRG3 are associated with delusions in patients with schizophrenia. In order to gain insights into the biological function of the gene, we generated a novel Nrg3 knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired prepulse inhibition of the acoustic startle response, and deficient fear conditioning...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606321/genetics-of-common-antipsychotic-induced-adverse-effects
#10
REVIEW
Raymond R MacNeil, Daniel J Müller
The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27429957/leukocyte-telomere-length-predicts-ssri-response-in-major-depressive-disorder-a-preliminary-report
#11
Christina M Hough, F Saverio Bersani, Synthia H Mellon, Elissa S Epel, Victor I Reus, Daniel Lindqvist, Jue Lin, Laura Mahan, Rebecca Rosser, Heather Burke, John Coetzee, J Craig Nelson, Elizabeth H Blackburn, Owen M Wolkowitz
Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, including major depressive disorder (MDD). Short LTL has previously been associated with poor response to psychiatric medications in bipolar disorder and schizophrenia, but no studies have prospectively assessed the relationship of LTL to SSRI response in MDD. We assessed pre-treatment LTL, depression severity (using the Hamilton Depression Rating Scale [HDRS]), and self-reported positive and negative affect in 27 healthy, unmedicated adults with MDD...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606320/fluoxetine-treatment-rescues-energy-metabolism-pathway-alterations-in-a-posttraumatic-stress-disorder-mouse-model
#12
Chi-Ya Kao, Zhisong He, Kathrin Henes, John M Asara, Christian Webhofer, Michaela D Filiou, Philipp Khaitovich, Carsten T Wotjak, Christoph W Turck
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606319/a-review-of-genome-wide-association-studies-of-stimulant-and-opioid-use-disorders
#13
REVIEW
Kevin P Jensen
Substance use disorders (SUD) are a major contributor to disability and disease burden worldwide. Risk for developing SUDs is influenced by variation in the genome. Identifying the genetic variants that influence SUD risk may help us to understand the biological mechanisms for the disorders and improve treatments. Genome-wide association studies (GWAS) have been successful in identifying many regions of the genome associated with common human disorders. Here, findings from recent GWAS of SUDs that involve illicit substances will be reviewed...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606318/cell-type-specific-effects-of-mutant-disc1-a-proteomics-study
#14
Meng Xia, Jantine A C Broek, Yan Jouroukhin, Jeannine Schoenfelder, Sofya Abazyan, Hanna Jaaro-Peled, Akira Sawa, Sabine Bahn, Mikhail Pletnikov
Despite the recent progress in psychiatric genetics, very few studies have focused on genetic risk factors in glial cells that, compared to neurons, can manifest different molecular pathologies underlying psychiatric disorders. In order to address this issue, we studied the effects of mutant disrupted in schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured primary neurons and astrocytes using an unbiased mass spectrometry-based proteomic approach. We found that selective expression of mutant DISC1 in neurons affects a wide variety of proteins predominantly involved in neuronal development (e...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606317/a-case-for-returning-to-multiplex-families-for-further-understanding-the-heritability-of-schizophrenia-a-psychiatrist-s-perspective
#15
Lynn E DeLisi
The genetic mechanism for schizophrenia still remains unknown despite decades of research. A tremendous amount of investigator time and effort has gone into ascertainment of clinical samples for genetic studies over the years. Most recently, a large international effort of unprecedented collaboration has occurred to combine data worldwide in pursuit of uncovering the relevant genetic risk factors. However, in the process, the use of multiplex families to understand the genetics has waned, and it has been presumed that large resources of unrelated patients and controls are more efficient to find risk alleles than families...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606316/inflammatory-cytokines-and-antipsychotic-induced-weight-gain-review-and-clinical-implications
#16
REVIEW
Trehani M Fonseka, Daniel J Müller, Sidney H Kennedy
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27602361/erratum
#17
(no author information available yet)
[This corrects the article DOI: 10.1159/000441252.].
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27525255/sumoylation-of-disc1-a-potential-role-in-neural-progenitor-proliferation-in-the-developing-cortex
#18
Stephanie Tankou, Kazuhiro Ishii, Christina Elliott, Krishna C Yalla, Jon P Day, Keiko Furukori, Ken-Ichiro Kubo, Nicholas J Brandon, Qiyi Tang, Gary Hayward, Kazunori Nakajima, Miles D Houslay, Atsushi Kamiya, George Baillie, Koko Ishizuka, Akira Sawa
DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy of modest evidence in genetics but strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606315/altered-brain-structure-function-relationships-underlie-executive-dysfunction-in-22q11-2-deletion-syndrome
#19
Rachel K Jonas, Maria Jalbrzikowski, Caroline A Montojo, Arati Patel, Leila Kushan, Carolyn C Chow, Therese Vesagas, Carrie E Bearden
22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF...
December 2015: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606314/snap-25a-b-isoform-levels-in-human-brain-dorsolateral-prefrontal-cortex-and-anterior-cingulate-cortex
#20
Peter M Thompson, Dianne A Cruz, Elizabeth A Fucich, Dianna Y Olukotun, Masami Takahashi, Makoto Itakura
SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness...
December 2015: Molecular Neuropsychiatry
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