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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28993711/social-impairments-in-autism-spectrum-disorder-are-related-to-maternal-immune-history-profile
#1
S Patel, A Masi, R C Dale, A J O Whitehouse, I Pokorski, G A Alvares, I B Hickie, E Breen, A J Guastella
Maternal immune activation has been highlighted as a factor that might increase the risk and severity of autism spectrum disorder (ASD) in children. Preclinical animal evidence shows that immune activation in mothers during pregnancy causes ASD-like behavioural traits in offspring. To this point, there has been no investigation of whether immune system activation in human mothers during pregnancy is associated with more severe symptoms in children with ASD. In this study, data from an existing ASD cohort (N=220) were analysed to investigate whether immune conditions in the mother were associated with greater severity of autism-related symptoms...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#2
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28972577/genome-wide-association-study-across-european-and-african-american-ancestries-identifies-a-snp-in-dnmt3b-contributing-to-nicotine-dependence
#3
D B Hancock, Y Guo, G W Reginsson, N C Gaddis, S M Lutz, R Sherva, A Loukola, C C Minica, C A Markunas, Y Han, K A Young, D F Gudbjartsson, F Gu, D W McNeil, B Qaiser, C Glasheen, S Olson, M T Landi, P A F Madden, L A Farrer, J Vink, N L Saccone, M C Neale, H R Kranzler, J McKay, R J Hung, C I Amos, M L Marazita, D I Boomsma, T B Baker, J Gelernter, J Kaprio, N E Caporaso, T E Thorgeirsson, J E Hokanson, L J Bierut, K Stefansson, E O Johnson
Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28972576/the-effects-of-ketamine-on-dopaminergic-function-meta-analysis-and-review-of-the-implications-for-neuropsychiatric-disorders
#4
REVIEW
M Kokkinou, A H Ashok, O D Howes
Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948974/a-upf3b-mutant-mouse-model-with-behavioral-and-neurogenesis-defects
#5
L Huang, E Y Shum, S H Jones, C-H Lou, J Dumdie, H Kim, A J Roberts, L A Jolly, J L Espinoza, D M Skarbrevik, M H Phan, H Cook-Andersen, N R Swerdlow, J Gecz, M F Wilkinson
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ)...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948973/gestational-diabetes-exacerbates-maternal-immune-activation-effects-in-the-developing-brain
#6
K M Money, T L Barke, A Serezani, M Gannon, K A Garbett, D M Aronoff, K Mirnics
Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948972/nimh-neuropsychiatric-genomics-crucial-foundational-accomplishments-and-the-extensive-challenges-that-remain
#7
D L Braff
No abstract text is available yet for this article.
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948971/purinergic-system-in-psychiatric-diseases
#8
REVIEW
A Cheffer, A R G Castillo, J Corrêa-Velloso, M C B Gonçalves, Y Naaldijk, I C Nascimento, G Burnstock, H Ulrich
Psychiatric disorders are debilitating diseases, affecting >80 million people worldwide. There are no causal cures for psychiatric disorders and available therapies only treat the symptoms. The etiology of psychiatric disorders is unknown, although it has been speculated to be a combination of environmental, stress and genetic factors. One of the neurotransmitter systems implicated in the biology of psychiatric disorders is the purinergic system. In this review, we performed a comprehensive search of the literature about the role and function of the purinergic system in the development and predisposition to psychiatric disorders, with a focus on depression, schizophrenia, bipolar disorder, autism, anxiety and attention deficit/hyperactivity disorder...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948970/predicting-educational-achievement-from-dna
#9
S Selzam, E Krapohl, S von Stumm, P F O'Reilly, K Rimfeld, Y Kovas, P S Dale, J J Lee, R Plomin
This corrects the article DOI: 10.1038/mp.2016.107.
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948969/n-3-polyunsaturated-fatty-acid-deprivation-in-rats-decreases-frontal-cortex-bdnf-via-a-p38-mapk-dependent-mechanism
#10
J S Rao, R N Ertley, H-J Lee, J C DeMar, J T Arnold, S I Rapoport, R P Bazinet
No abstract text is available yet for this article.
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948968/stem-cell-derived-neurons-from-autistic-individuals-with-shank3-mutation-show-morphogenetic-abnormalities-during-early-development
#11
A Kathuria, P Nowosiad, R Jagasia, S Aigner, R D Taylor, L C Andreae, N J F Gatford, W Lucchesi, D P Srivastava, J Price
Shank3 is a structural protein found predominantly at the postsynaptic density. Mutations in the SHANK3 gene have been associated with risk for autism spectrum disorder (ASD). We generated induced pluripotent stem cells (iPSCs) from control individuals and from human donors with ASD carrying microdeletions of SHANK3. In addition, we used Zinc finger nucleases to generate isogenic SHANK3 knockout human embryonic stem (ES) cell lines. We differentiated pluripotent cells into either cortical or olfactory placodal neurons...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28948967/corticostriatal-circuit-defects-in-hoxb8-mutant-mice
#12
N Nagarajan, B W Jones, P J West, R E Marc, M R Capecchi
Hoxb8 mutant mice exhibit compulsive grooming and hair removal dysfunction similar to humans with the obsessive-compulsive disorder (OCD)-spectrum disorder, trichotillomania. As, in the mouse brain, the only detectable cells that label with Hoxb8 cell lineage appear to be microglia, we suggested that defective microglia cause the neuropsychiatric disorder. Does the Hoxb8 mutation in microglia lead to neural circuit dysfunctions? We demonstrate that Hoxb8 mutants contain corticostriatal circuit defects. Golgi staining, ultra-structural and electrophysiological studies of mutants reveal excess dendritic spines, pre- and postsynaptic structural defects, long-term potentiation and miniature postsynaptic current defects...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924188/dopamine-d1-receptor-subtype-mediates-acute-stress-induced-dendritic-growth-in-excitatory-neurons-of-the-medial-prefrontal-cortex-and-contributes-to-suppression-of-stress-susceptibility-in-mice
#13
R Shinohara, M Taniguchi, A T Ehrlich, K Yokogawa, Y Deguchi, Y Cherasse, M Lazarus, Y Urade, A Ogawa, S Kitaoka, A Sawa, S Narumiya, T Furuyashiki
Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924187/the-ipsych2012-case-cohort-sample-new-directions-for-unravelling-genetic-and-environmental-architectures-of-severe-mental-disorders
#14
C B Pedersen, J Bybjerg-Grauholm, M G Pedersen, J Grove, E Agerbo, M Bækvad-Hansen, J B Poulsen, C S Hansen, J J McGrath, T D Als, J I Goldstein, B M Neale, M J Daly, D M Hougaard, O Mors, M Nordentoft, A D Børglum, T Werge, P B Mortensen
The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924186/interactome-analysis-reveals-znf804a-a-schizophrenia-risk-gene-as-a-novel-component-of-protein-translational-machinery-critical-for-embryonic-neurodevelopment
#15
Y Zhou, F Dong, T A Lanz, V Reinhart, M Li, L Liu, J Zou, H S Xi, Y Mao
Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924185/5-httlpr-%C3%A3-stress-hypothesis-is-the-debate-over
#16
M-L Ancelin, J Ryan
No abstract text is available yet for this article.
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924184/genetic-contributions-to-trail-making-test-performance-in-uk-biobank
#17
S P Hagenaars, S R Cox, W D Hill, G Davies, D C M Liewald, S E Harris, A M McIntosh, C R Gale, I J Deary
The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924183/the-associations-of-earlier-trauma-exposures-and-history-of-mental-disorders-with-ptsd-after-subsequent-traumas
#18
R C Kessler, S Aguilar-Gaxiola, J Alonso, E J Bromet, O Gureje, E G Karam, K C Koenen, S Lee, H Liu, B-E Pennell, M V Petukhova, N A Sampson, V Shahly, D J Stein, L Atwoli, G Borges, B Bunting, G de Girolamo, S F Gluzman, J M Haro, H Hinkov, N Kawakami, V Kovess-Masfety, F Navarro-Mateu, J Posada-Villa, K M Scott, A Y Shalev, M Ten Have, Y Torres, M C Viana, A M Zaslavsky
Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924182/an-in-vitro-model-of-lissencephaly-expanding-the-role-of-dcx-during-neurogenesis
#19
M Shahsavani, R J Pronk, R Falk, M Lam, M Moslem, S B Linker, J Salma, K Day, J Schuster, B-M Anderlid, N Dahl, F H Gage, A Falk
Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924181/common-and-dissociable-regional-cerebral-blood-flow-differences-associate-with-dimensions-of-psychopathology-across-categorical-diagnoses
#20
A N Kaczkurkin, T M Moore, M E Calkins, R Ciric, J A Detre, M A Elliott, E B Foa, A Garcia de la Garza, D R Roalf, A Rosen, K Ruparel, R T Shinohara, C H Xia, D H Wolf, R E Gur, R C Gur, T D Satterthwaite
The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1042 youths (ages 11-23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort...
September 19, 2017: Molecular Psychiatry
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