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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28727688/diazepam-actions-in-the-vta-enhance-social-dominance-and-mitochondrial-function-in-the-nucleus-accumbens-by-activation-of-dopamine-d1-receptors
#1
M A van der Kooij, F Hollis, L Lozano, I Zalachoras, S Abad, O Zanoletti, J Grosse, I Guillot de Suduiraut, C Canto, C Sandi
Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28727687/hippocampus-dependent-memory-and-allele-specific-gene-expression-in-adult-offspring-of-alcohol-consuming-dams-after-neonatal-treatment-with-thyroxin-or-metformin
#2
E Tunc-Ozcan, S L Wert, P H Lim, A Ferreira, E E Redei
Fetal alcohol spectrum disorder (FASD), the result of fetal alcohol exposure (FAE), affects 2-11% of children worldwide, with no effective treatments. Hippocampus-based learning and memory deficits are key symptoms of FASD. Our previous studies show hypothyroxinemia and hyperglycemia of the alcohol-consuming pregnant rat, which likely affects fetal neurodevelopment. We administered vehicle, thyroxine (T4) or metformin to neonatal rats post FAE and rats were tested in the hippocampus-dependent contextual fear-conditioning paradigm in adulthood...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28727686/fbxw7-regulates-disc1-stability-via-the-ubiquitin-proteosome-system
#3
K Yalla, C Elliott, J P Day, J Findlay, S Barratt, Z A Hughes, L Wilson, E Whiteley, M Popiolek, Y Li, J Dunlop, R Killick, D R Adams, N J Brandon, M D Houslay, B Hao, G S Baillie
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#4
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#5
R Lu, J Wang, R Tao, J Wang, T Zhu, W Guo, Y Sun, H Li, Y Gao, W Zhang, C J Fowler, Q Li, S Chen, Z Wu, C L Masters, C Zhong, N Jing, Y Wang, Y Wang
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696435/a-direct-test-of-the-diathesis-stress-model-for-depression
#6
L Colodro-Conde, B Couvy-Duchesne, G Zhu, W L Coventry, E M Byrne, S Gordon, M J Wright, G W Montgomery, P A F Madden, S Ripke, L J Eaves, A C Heath, N R Wray, S E Medland, N G Martin
The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696434/when-should-governments-increase-the-supply-of-psychiatric-beds
#7
S Allison, T Bastiampillai, J Licinio, D A Fuller, N Bidargaddi, S S Sharfstein
Low numbers of hospital-based psychiatric beds create problems for people with severe mental illness (SMI), when they face extended emergency department (ED) waits, higher thresholds for admission to an acute bed, and short revolving-door stays with high rates of rehospitalisation. Limited access to inpatient treatment has been associated with higher suicide risk, premature mortality, homelessness, violent crime and incarceration. Ultimately, people with SMI can be transinstitutionalised to the criminal justice system...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696433/elevated-plasma-ferritin-in-elderly-individuals-with-high-neocortical-amyloid-%C3%AE-load
#8
K Goozee, P Chatterjee, I James, K Shen, H R Sohrabi, P R Asih, P Dave, C ManYan, K Taddei, S J Ayton, M L Garg, J B Kwok, A I Bush, R Chung, J S Magnussen, R N Martins
Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-β load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696432/cross-disorder-risk-gene-cacna1c-differentially-modulates-susceptibility-to-psychiatric-disorders-during-development-and-adulthood
#9
N Dedic, M L Pöhlmann, J S Richter, D Mehta, D Czamara, M W Metzger, J Dine, B T Bedenk, J Hartmann, K V Wagner, A Jurik, L M Almli, A Lori, S Moosmang, F Hofmann, C T Wotjak, G Rammes, M Eder, A Chen, K J Ressler, W Wurst, M V Schmidt, E B Binder, J M Deussing
Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression. However, genetic variants of complex diseases often only confer a marginal increase in disease risk, which is additionally influenced by the environment. Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696431/synaptic-activity-protects-against-ad-and-ftd-like-pathology-via-autophagic-lysosomal-degradation
#10
Y Akwa, E Gondard, A Mann, E Capetillo-Zarate, E Alberdi, C Matute, S Marty, T Vaccari, A M Lozano, E E Baulieu, D Tampellini
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696430/neuropathology-of-suicide-recent-findings-and-future-directions
#11
P-E Lutz, N Mechawar, G Turecki
Suicide is a major public health concern and a leading cause of death in most societies. Suicidal behaviour is complex and heterogeneous, likely resulting from several causes. It associates with multiple factors, including psychopathology, personality traits, early-life adversity and stressful life events, among others. Over the past decades, studies in fields ranging from neuroanatomy, genetics and molecular psychiatry have led to a model whereby behavioural dysregulation, including suicidal behaviour (SB), develops as a function of biological adaptations in key brain systems...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696429/glud1-linked-to-schizophrenia-controls-the-burst-firing-of-dopamine-neurons
#12
N Benamer, F Marti, R Lujan, R Hepp, T G Aubier, A A M Dupin, G Frébourg, S Pons, U Maskos, P Faure, Y A Hay, B Lambolez, L Tricoire
Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28630456/rare-disruptive-variants-in-the-disc1-interactome-and-regulome-association-with-cognitive-ability-and-schizophrenia
#13
S Teng, P A Thomson, S McCarthy, M Kramer, S Muller, J Lihm, S Morris, D C Soares, W Hennah, S Harris, L M Camargo, V Malkov, A M McIntosh, J K Millar, D H Blackwood, K L Evans, I J Deary, D J Porteous, W R McCombie
Schizophrenia (SCZ), bipolar disorder (BD) and recurrent major depressive disorder (rMDD) are common psychiatric illnesses. All have been associated with lower cognitive ability, and show evidence of genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism. Disrupted in schizophrenia 1 (DISC1) protein directly interacts with a large set of proteins (DISC1 Interactome) that are involved in brain development and signaling. Modulation of DISC1 expression alters the expression of a circumscribed set of genes (DISC1 Regulome) that are also implicated in brain biology and disorder...
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28630455/autism-spectrum-disorders-and-autistic-traits-share-genetics-and-biology
#14
J Bralten, K J van Hulzen, M B Martens, T E Galesloot, A Arias Vasquez, L A Kiemeney, J K Buitelaar, J W Muntjewerff, B Franke, G Poelmans
This corrects the article DOI: 10.1038/mp.2017.98.
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28630454/treatment-with-a-non-toxic-self-replicating-anti-prion-delays-or-prevents-prion-disease-in-vivo
#15
R Diaz-Espinoza, R Morales, L Concha-Marambio, I Moreno-Gonzalez, F Moda, C Soto
Transmissible spongiform encephalopathies (TSEs) are fatal neurological disorders caused by prions, which are composed of a misfolded protein (PrP(Sc)) that self-propagates in the brain of infected individuals by converting the normal prion protein (PrP(C)) into the pathological isoform. Here, we report a novel experimental strategy for preventing prion disease based on producing a self-replicating, but innocuous PrP(Sc)-like form, termed anti-prion, which can compete with the replication of pathogenic prions...
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28630453/longitudinal-analyses-of-the-dna-methylome-in-deployed-military-servicemen-identify-susceptibility-loci-for-post-traumatic-stress-disorder
#16
B P F Rutten, E Vermetten, C H Vinkers, G Ursini, N P Daskalakis, E Pishva, L de Nijs, L C Houtepen, L Eijssen, A E Jaffe, G Kenis, W Viechtbauer, D van den Hove, K G Schraut, K-P Lesch, J E Kleinman, T M Hyde, D R Weinberger, L Schalkwyk, K Lunnon, J Mill, H Cohen, R Yehuda, D G Baker, A X Maihofer, C M Nievergelt, E Geuze, M P M Boks
In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions...
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28630452/remote-memories-are-enhanced-by-comt-activity-through-dysregulation-of-the-endocannabinoid-system-in-the-prefrontal-cortex
#17
D Scheggia, E Zamberletti, N Realini, M Mereu, G Contarini, V Ferretti, F Managò, G Margiani, R Brunoro, T Rubino, M A De Luca, D Piomelli, D Parolaro, F Papaleo
The prefrontal cortex (PFC) is a crucial hub for the flexible modulation of recent memories (executive functions) as well as for the stable organization of remote memories. Dopamine in the PFC is implicated in both these processes and genetic variants affecting its neurotransmission might control the unique balance between cognitive stability and flexibility present in each individual. Functional genetic variants in the catechol-O-methyltransferase (COMT) gene result in a different catabolism of dopamine in the PFC...
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28607459/the-arf6-activator-efa6-psd3-confers-regional-specificity-and-modulates-ethanol-consumption-in-drosophila-and-humans
#18
D A Gonzalez, T Jia, J H Pinzón, S F Acevedo, S A Ojelade, B Xu, N Tay, S Desrivières, J L Hernandez, T Banaschewski, C Büchel, A L W Bokde, P J Conrod, H Flor, V Frouin, J Gallinat, H Garavan, P A Gowland, A Heinz, B Ittermann, M Lathrop, J-L Martinot, T Paus, M N Smolka, A R Rodan, G Schumann, A Rothenfluh
Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies...
June 13, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28607458/prenatal-fever-and-autism-risk
#19
M Hornig, M A Bresnahan, X Che, A F Schultz, J E Ukaigwe, M L Eddy, D Hirtz, N Gunnes, K K Lie, P Magnus, S Mjaaland, T Reichborn-Kjennerud, S Schjølberg, A-S Øyen, B Levin, E S Susser, C Stoltenberg, W I Lipkin
Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression...
June 13, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28584286/genome-wide-meta-analysis-of-cognitive-empathy-heritability-and-correlates-with-sex-neuropsychiatric-conditions-and-cognition
#20
V Warrier, K L Grasby, F Uzefovsky, R Toro, P Smith, B Chakrabarti, J Khadake, E Mawbey-Adamson, N Litterman, J-J Hottenga, G Lubke, D I Boomsma, N G Martin, P K Hatemi, S E Medland, D A Hinds, T Bourgeron, S Baron-Cohen
We conducted a genome-wide meta-analysis of cognitive empathy using the 'Reading the Mind in the Eyes' Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen's d=0.21, P<2.2 × 10(-16)), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, Pmeta=1...
June 6, 2017: Molecular Psychiatry
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