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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28630456/rare-disruptive-variants-in-the-disc1-interactome-and-regulome-association-with-cognitive-ability-and-schizophrenia
#1
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/28630454/treatment-with-a-non-toxic-self-replicating-anti-prion-delays-or-prevents-prion-disease-in-vivo
#2
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
#3
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
#4
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/28608853/genetic-tests-in-major-psychiatric-disorders-integrating-molecular-medicine-with-clinical-psychiatry-why-is-it-so-difficult
#5
REVIEW
U Demkow, T Wolańczyk
With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays' medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping)...
June 13, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28607459/the-arf6-activator-efa6-psd3-confers-regional-specificity-and-modulates-ethanol-consumption-in-drosophila-and-humans
#6
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
#7
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/28584287/rescue-of-impaired-sociability-and-anxiety-like-behavior-in-adult-cacna1c-deficient-mice-by-pharmacologically-targeting-eif2%C3%AE
#8
Z D Kabir, A Che, D K Fischer, R C Rice, B K Rizzo, M Byrne, M J Glass, N V De Marco Garcia, A M Rajadhyaksha
CACNA1C, encoding the Cav1.2 subunit of L-type Ca(2+) channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1...
June 6, 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
#9
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
https://www.readbyqxmd.com/read/28555078/tau-dependent-suppression-of-adult-neurogenesis-in-the-stressed-hippocampus
#10
C Dioli, P Patrício, R Trindade, L G Pinto, J M Silva, M Morais, E Ferreiro, S Borges, A Mateus-Pinheiro, A J Rodrigues, N Sousa, J M Bessa, L Pinto, I Sotiropoulos
Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role(s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates...
May 30, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28555077/the-dendritic-spine-morphogenic-effects-of-repeated-cocaine-use-occur-through-the-regulation-of-serum-response-factor-signaling
#11
M E Cahill, D M Walker, A M Gancarz, Z J Wang, C K Lardner, R C Bagot, R L Neve, D M Dietz, E J Nestler
The nucleus accumbens (NAc) is a primary brain reward region composed predominantly of medium spiny neurons (MSNs). In response to early withdrawal from repeated cocaine administration, de novo dendritic spine formation occurs in NAc MSNs. Much evidence indicates that this new spine formation facilitates the rewarding properties of cocaine. Early withdrawal from repeated cocaine also produces dramatic alterations in the transcriptome of NAc MSNs, but how such alterations influence cocaine's effects on dendritic spine formation remain unclear...
May 30, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28555076/comparative-genomic-evidence-for-the-involvement-of-schizophrenia-risk-genes-in-antipsychotic-effects
#12
Y Kim, P Giusti-Rodriguez, J J Crowley, J Bryois, R J Nonneman, A K Ryan, C R Quackenbush, M D Iglesias-Ussel, P H Lee, W Sun, F P-M de Villena, P F Sullivan
Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D2, are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo molecular approach to this question by performing RNA sequencing of brain tissue from mice chronically treated with the antipsychotic haloperidol or vehicle. We observed significant enrichments of haloperidol-regulated genes in schizophrenia GWAS loci and in schizophrenia-associated biological pathways...
May 30, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28555075/acute-ketamine-administration-corrects-abnormal-inflammatory-bone-markers-in-major-depressive-disorder
#13
B Kadriu, P W Gold, D A Luckenbaugh, M S Lener, E D Ballard, M J Niciu, I D Henter, L T Park, R T De Sousa, P Yuan, R Machado-Vieira, C A Zarate
Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD...
May 30, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28533517/vortioxetine-reduces-bold-signal-during-performance-of-the-n-back-working-memory-task-a-randomised-neuroimaging-trial-in-remitted-depressed-patients-and-healthy-controls
#14
J Smith, M Browning, S Conen, R Smallman, J Buchbjerg, K G Larsen, C K Olsen, S R Christensen, G R Dawson, J F Deakin, P Hawkins, R Morris, G Goodwin, C J Harmer
Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed (n=48) and healthy volunteers (n=48) were randomised to receive 14 days treatment with 20 mg vortioxetine or placebo in a double-blind design...
May 23, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28533516/asd-restricted-and-repetitive-behaviors-associated-at-17q21-33-genes-prioritized-by-expression-in-fetal-brains
#15
R M Cantor, L Navarro, H Won, R L Walker, J K Lowe, D H Geschwind
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP)...
May 23, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28507321/pet-imaging-of-dopamine-d2-receptor-internalization-in-schizophrenia
#16
J J Weinstein, E van de Giessen, R J Rosengard, X Xu, N Ojeil, G Brucato, R B Gil, L S Kegeles, M Laruelle, M Slifstein, A Abi-Dargham
Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28507320/the-microbiome-regulates-amygdala-dependent-fear-recall
#17
A E Hoban, R M Stilling, G Moloney, F Shanahan, T G Dinan, G Clarke, J F Cryan
The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome-gut-brain in regulating anxiety and stress-related responses. However, the role of the microbiome in fear-related behaviours is unclear. To this end we investigated the importance of the host microbiome on amygdala-dependent behavioural readouts using the cued fear conditioning paradigm...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28507319/longitudinal-changes-of-tau-pet-imaging-in-relation-to-hypometabolism-in-prodromal-and-alzheimer-s-disease-dementia
#18
K Chiotis, L Saint-Aubert, E Rodriguez-Vieitez, A Leuzy, O Almkvist, I Savitcheva, M Jonasson, M Lubberink, A Wall, G Antoni, A Nordberg
The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [(18)F]THK5317 (tau deposition) and [(18)F]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [(11)C]PIB (amyloid-β deposition) at baseline only...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28507318/cerebellar-volume-and-cerebellocerebral-structural-covariance-in-schizophrenia-a-multisite-mega-analysis-of-983-patients-and-1349-healthy-controls
#19
T Moberget, N T Doan, D Alnæs, T Kaufmann, A Córdova-Palomera, T V Lagerberg, J Diedrichsen, E Schwarz, M Zink, S Eisenacher, P Kirsch, E G Jönsson, H Fatouros-Bergman, L Flyckt, G Pergola, T Quarto, A Bertolino, D Barch, A Meyer-Lindenberg, I Agartz, O A Andreassen, L T Westlye
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28507317/elevation-of-p11-in-lateral-habenula-mediates-depression-like-behavior
#20
J-S Seo, P Zhong, A Liu, Z Yan, P Greengard
The lateral habenula (LHb) is a key brain region involved in the pathophysiology of depression. It is activated by stimuli associated with negative experiences and is involved in encoding aversive signals. Hyperactivity of LHb is found in both rodent models of depression and human patients with depression. However, little is known about the underlying molecular mechanisms. Here we show that in LHb neurons, p11, a multifunctional protein implicated in depression, is significantly upregulated by chronic restraint stress...
May 16, 2017: Molecular Psychiatry
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