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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28533518/blocking-crmp2-sumoylation-reverses-neuropathic-pain
#1
A Moutal, E T Dustrude, T M Largent-Milnes, T W Vanderah, M Khanna, R Khanna
No abstract text is available yet for this article.
May 23, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28507316/autism-spectrum-disorders-and-autistic-traits-share-genetics-and-biology
#9
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
Autism spectrum disorders (ASDs) and autistic traits in the general population may share genetic susceptibility factors. In this study, we investigated such potential overlap based on common genetic variants. We developed and validated a self-report questionnaire of autistic traits in adults. We then conducted genome-wide association studies (GWASs) of six trait scores derived from the questionnaire through exploratory factor analysis in 1981 adults from the general population. Using the results from the Psychiatric Genomics Consortium GWAS of ASDs, we observed genetic sharing between ASDs and the autistic traits 'childhood behavior', 'rigidity' and 'attention to detail'...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485408/genetic-and-pharmacological-antagonism-of-nk1-receptor-prevents-opiate-abuse-potential
#10
A J Sandweiss, M I McIntosh, A Moutal, R Davidson-Knapp, J Hu, A K Giri, T Yamamoto, V J Hruby, R Khanna, T M Largent-Milnes, T W Vanderah
Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK1R) in the VTA renders morphine non-rewarding...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485407/lipocalin-2-regulates-adult-neurogenesis-and-contextual-discriminative-behaviours
#11
A C Ferreira, T Santos, B Sampaio-Marques, A Novais, S D Mesquita, P Ludovico, L Bernardino, M Correia-Neves, N Sousa, J A Palha, J C Sousa, F Marques
In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485406/inducing-a-long-term-potentiation-in-the-dentate-gyrus-is-sufficient-to-produce-rapid-antidepressant-like-effects
#12
A Kanzari, C Bourcier-Lucas, A Freyssin, D N Abrous, N Haddjeri, G Lucas
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485405/investigating-the-neuroimmunogenic-architecture-of-schizophrenia
#13
R Birnbaum, A E Jaffe, Q Chen, J H Shin, J E Kleinman, T M Hyde, D R Weinberger
The role of the immune system in schizophrenia remains controversial despite numerous studies to date. Most studies have profiled expression of select genes or proteins in peripheral blood, but none have focused on the expression of canonical pathways that mediate overall immune response. The current study used a systematic genetic approach to investigate the role of the immune system in a large sample of post-mortem brain of patients with schizophrenia: RNA sequencing was performed to assess the differential expression of 561 immune genes and 20 immune pathways in dorsolateral prefrontal cortex (DLPFC) (144 schizophrenia and 196 control subjects) and hippocampus (83 schizophrenia and 187 control subjects)...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485404/genetic-contributors-to-variation-in-alcohol-consumption-vary-by-race-ethnicity-in-a-large-multi-ethnic-genome-wide-association-study
#14
E Jorgenson, K K Thai, T J Hoffmann, L C Sakoda, M N Kvale, Y Banda, C Schaefer, N Risch, J Mertens, C Weisner, H Choquet
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28485403/gad1-alternative-transcripts-and-dna-methylation-in-human-prefrontal-cortex-and-hippocampus-in-brain-development-schizophrenia
#15
R Tao, K N Davis, C Li, J H Shin, Y Gao, A E Jaffe, M C Gondré-Lewis, D R Weinberger, J E Kleinman, T M Hyde
Genetic variations and adverse environmental events in utero or shortly after birth can lead to abnormal brain development and increased risk of schizophrenia. γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, plays a vital role in normal brain development. GABA synthesis is controlled by enzymes derived from two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce transcript isoforms. While the full-length GAD1 transcript (GAD67) has been implicated in the neuropathology of schizophrenia, the transcript structure of GAD1 in the human brain has not been fully characterized...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461701/activation-of-a-novel-p70-s6-kinase-1-dependent-intracellular-cascade-in-the-basolateral-nucleus-of-the-amygdala-is-required-for-the-acquisition-of-extinction-memory
#16
T N Huynh, E Santini, E Mojica, A E Fink, B S Hall, R N Fetcho, L Grosenick, K Deisseroth, J E LeDoux, C Liston, E Klann
Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461700/connectome-imaging-for-mapping-human-brain-pathways
#17
Y Shi, A W Toga
With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461699/cortical-abnormalities-in-bipolar-disorder-an-mri-analysis-of-6503-individuals-from-the-enigma-bipolar-disorder-working-group
#18
D P Hibar, L T Westlye, N T Doan, N Jahanshad, J W Cheung, C R K Ching, A Versace, A C Bilderbeck, A Uhlmann, B Mwangi, B Krämer, B Overs, C B Hartberg, C Abé, D Dima, D Grotegerd, E Sprooten, E Bøen, E Jimenez, F M Howells, G Delvecchio, H Temmingh, J Starke, J R C Almeida, J M Goikolea, J Houenou, L M Beard, L Rauer, L Abramovic, M Bonnin, M F Ponteduro, M Keil, M M Rive, N Yao, N Yalin, P Najt, P G Rosa, R Redlich, S Trost, S Hagenaars, S C Fears, S Alonso-Lana, T G M van Erp, T Nickson, T M Chaim-Avancini, T B Meier, T Elvsåshagen, U K Haukvik, W H Lee, A H Schene, A J Lloyd, A H Young, A Nugent, A M Dale, A Pfennig, A M McIntosh, B Lafer, B T Baune, C J Ekman, C A Zarate, C E Bearden, C Henry, C Simhandl, C McDonald, C Bourne, D J Stein, D H Wolf, D M Cannon, D C Glahn, D J Veltman, E Pomarol-Clotet, E Vieta, E J Canales-Rodriguez, F G Nery, F L S Duran, G F Busatto, G Roberts, G D Pearlson, G M Goodwin, H Kugel, H C Whalley, H G Ruhe, J C Soares, J M Fullerton, J K Rybakowski, J Savitz, K T Chaim, M Fatjó-Vilas, M G Soeiro-de-Souza, M P Boks, M V Zanetti, M C G Otaduy, M S Schaufelberger, M Alda, M Ingvar, M L Phillips, M J Kempton, M Bauer, M Landén, N S Lawrence, N E M van Haren, N R Horn, N B Freimer, O Gruber, P R Schofield, P B Mitchell, R S Kahn, R Lenroot, R Machado-Vieira, R A Ophoff, S Sarró, S Frangou, T D Satterthwaite, T Hajek, U Dannlowski, U F Malt, V Arolt, W F Gattaz, W C Drevets, X Caseras, I Agartz, P M Thompson, O A Andreassen
Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461698/genetic-risk-for-schizophrenia-and-psychosis-in-alzheimer-disease
#19
M A A DeMichele-Sweet, E A Weamer, L Klei, D T Vrana, D J Hollingshead, H J Seltman, R Sims, T Foroud, I Hernandez, S Moreno-Grau, L Tárraga, M Boada, A Ruiz, J Williams, R Mayeux, O L Lopez, E L Sibille, M I Kamboh, B Devlin, R A Sweet
Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115)...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28461697/exocytosis-related-genes-and-response-to-methylphenidate-treatment-in-adults-with-adhd
#20
B S da Silva, R B Cupertino, D L Rovaris, J B Schuch, D B Kappel, D Müller, C E Bandeira, M M Victor, R G Karam, N R Mota, L A Rohde, V Contini, E H Grevet, C H D Bau
Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD...
May 2, 2017: Molecular Psychiatry
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