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Molecular Psychiatry

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https://www.readbyqxmd.com/read/27922608/peripheral-administration-of-lactate-produces-antidepressant-like-effects
#1
A Carrard, M Elsayed, M Margineanu, B Boury-Jamot, L Fragnière, E M Meylan, J-M Petit, H Fiumelli, P J Magistretti, J-L Martin
No abstract text is available yet for this article.
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922607/endocytosis-following-dopamine-d2-receptor-activation-is-critical-for-neuronal-activity-and-dendritic-spine-formation-via-rabex-5-pdgfr%C3%AE-signaling-in-striatopallidal-medium-spiny-neurons
#2
N Shioda, Y Yabuki, Y Wang, M Uchigashima, T Hikida, T Sasaoka, H Mori, M Watanabe, M Sasahara, K Fukunaga
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-β (PDGFRβ)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922606/otto-a-new-strategy-to-extract-mental-disease-relevant-combinations-of-gwas-hits-from-individuals
#3
H Ehrenreich, M Mitjans, S Van der Auwera, T P Centeno, M Begemann, H J Grabe, S Bonn, K-A Nave
Despite high heritability of schizophrenia, genome-wide association studies (GWAS) have not yet revealed distinct combinations of single-nucleotide polymorphisms (SNPs), relevant for mental disease-related, quantifiable behavioral phenotypes. Here we propose an individual-based model to use genome-wide significant markers for extracting first genetic signatures of such behavioral continua. 'OTTO' (old Germanic=heritage) marks an individual characterized by a prominent phenotype and a particular load of phenotype-associated risk SNPs derived from GWAS that likely contributed to the development of his personal mental illness...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922605/pattern-of-structural-brain-changes-in-social-anxiety-disorder-after-cognitive-behavioral-group-therapy-a-longitudinal-multimodal-mri-study
#4
V R Steiger, A B Brühl, S Weidt, A Delsignore, M Rufer, L Jäncke, U Herwig, J Hänggi
Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM)...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922604/common-variants-on-2p16-1-6p22-1-and-10q24-32-are-associated-with-schizophrenia-in-han-chinese-population
#5
H Yu, H Yan, J Li, Z Li, X Zhang, Y Ma, L Mei, C Liu, L Cai, Q Wang, F Zhang, N Iwata, M Ikeda, L Wang, T Lu, M Li, H Xu, X Wu, B Liu, J Yang, K Li, L Lv, X Ma, C Wang, L Li, F Yang, T Jiang, Y Shi, T Li, D Zhang, W Yue
Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922603/digital-footprints-facilitating-large-scale-environmental-psychiatric-research-in-naturalistic-settings-through-data-from-everyday-technologies
#6
N Bidargaddi, P Musiat, V-P Makinen, M Ermes, G Schrader, J Licinio
Digital footprints, the automatically accumulated by-products of our technology-saturated lives, offer an exciting opportunity for psychiatric research. The commercial sector has already embraced the electronic trails of customers as an enabling tool for guiding consumer behaviour, and analogous efforts are ongoing to monitor and improve the mental health of psychiatric patients. The untargeted collection of digital footprints that may or may not be health orientated comprises a large untapped information resource for epidemiological scale research into psychiatric disorders...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27895323/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#7
M M Jukić, N Opel, J Ström, T Carrillo-Roa, S Miksys, M Novalen, A Renblom, S C Sim, E M Peñas-Lledó, P Courtet, A Llerena, B T Baune, D J de Quervain, A Papassotiropoulos, R F Tyndale, E B Binder, U Dannlowski, M Ingelman-Sundberg
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype...
November 29, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27895322/gestational-vitamin-d-deficiency-and-autism-related-traits-the-generation-r-study
#8
A A E Vinkhuyzen, D W Eyles, T H J Burne, L M E Blanken, C J Kruithof, F Verhulst, V W Jaddoe, H Tiemeier, J J McGrath
There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229)...
November 29, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27872486/alpha-2-macroglobulin-in-alzheimer-s-disease-a-marker-of-neuronal-injury-through-the-rcan1-pathway
#9
V R Varma, S Varma, Y An, T J Hohman, S Seddighi, R Casanova, A Beri, E B Dammer, N T Seyfried, O Pletnikova, A Moghekar, M R Wilson, J J Lah, R J O'Brien, A I Levey, J C Troncoso, M S Albert, M Thambisetty
Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort...
November 22, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843154/the-nf-%C3%AE%C2%BAb-signaling-pathway-an-important-therapeutic-target-in-psychiatric-disorders
#10
M A Altinoz, B Ince, C Tek, V H Srihari, S Guloksuz
No abstract text is available yet for this article.
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843153/predictive-analytics-in-mental-health-applications-guidelines-challenges-and-perspectives
#11
T Hahn, A A Nierenberg, S Whitfield-Gabrieli
The emerging field of 'predictive analytics in mental health' has recently generated tremendous interest with the bold promise to revolutionize clinical practice in psychiatry paralleling similar developments in personalized and precision medicine. Here, we provide an overview of the key questions and challenges in the field, aiming to (1) propose general guidelines for predictive analytics projects in psychiatry, (2) provide a conceptual introduction to core aspects of predictive modeling technology, and (3) foster a broad and informed discussion involving all stakeholders including researchers, clinicians, patients, funding bodies and policymakers...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843152/additive-effects-of-oxytocin-receptor-gene-polymorphisms-on-reward-circuitry-in-youth-with-autism
#12
L M Hernandez, K Krasileva, S A Green, L E Sherman, C Ponting, R McCarron, J K Lowe, D H Geschwind, S Y Bookheimer, M Dapretto
Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843151/a-dna-methylation-biomarker-of-alcohol-consumption
#13
C Liu, R E Marioni, Å K Hedman, L Pfeiffer, P-C Tsai, L M Reynolds, A C Just, Q Duan, C G Boer, T Tanaka, C E Elks, S Aslibekyan, J A Brody, B Kühnel, C Herder, L M Almli, D Zhi, Y Wang, T Huan, C Yao, M M Mendelson, R Joehanes, L Liang, S-A Love, W Guan, S Shah, A F McRae, A Kretschmer, H Prokisch, K Strauch, A Peters, P M Visscher, N R Wray, X Guo, K L Wiggins, A K Smith, E B Binder, K J Ressler, M R Irvin, D M Absher, D Hernandez, L Ferrucci, S Bandinelli, K Lohman, J Ding, L Trevisi, S Gustafsson, J H Sandling, L Stolk, A G Uitterlinden, I Yet, J E Castillo-Fernandez, T D Spector, J D Schwartz, P Vokonas, L Lind, Y Li, M Fornage, D K Arnett, N J Wareham, N Sotoodehnia, K K Ong, J B J van Meurs, K N Conneely, A A Baccarelli, I J Deary, J T Bell, K E North, Y Liu, M Waldenberger, S J London, E Ingelsson, D Levy
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843150/the-bacterial-peptidoglycan-sensing-molecule-pglyrp2-modulates-brain-development-and-behavior
#14
T Arentsen, Y Qian, S Gkotzis, T Femenia, T Wang, K Udekwu, H Forssberg, R Diaz Heijtz
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843149/jnk1-controls-adult-hippocampal-neurogenesis-and-imposes-cell-autonomous-control-of-anxiety-behaviour-from-the-neurogenic-niche
#15
H Mohammad, F Marchisella, S Ortega-Martinez, P Hollos, K Eerola, E Komulainen, N Kulesskaya, E Freemantle, V Fagerholm, E Savontous, H Rauvala, B D Peterson, H van Praag, E T Coffey
Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843148/hypervulnerability-of-the-adolescent-prefrontal-cortex-to-nutritional-stress-via-reelin-deficiency
#16
M A Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter, T Gschwind, L Pujadas, E Soriano, A C Reichelt, C Labouesse, W Langhans, P Chavis, U Meyer
Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN(+) cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843147/a-new-pathway-for-the-gut-microbiota-to-modulate-the-brain-activation-of-pattern-recognition-receptors-by-microbial-products
#17
P Zheng, K Cheng, L Zeng, C-J Zhou, P Xie
No abstract text is available yet for this article.
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27821870/disinhibition-of-somatostatin-positive-gabaergic-interneurons-results-in-an-anxiolytic-and-antidepressant-like-brain-state
#18
T Fuchs, S J Jefferson, A Hooper, P-Hp Yee, J Maguire, B Luscher
Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons...
November 8, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27821869/challenges-in-conducting-genetic-analyses-based-on-data-driven-classification-of-major-depressive-disorder
#19
V-P Mäkinen
No abstract text is available yet for this article.
November 8, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27821868/problems-with-latent-class-analysis-to-detect-data-driven-subtypes-of-depression
#20
H M van Loo, R B K Wanders, K J Wardenaar, E I Fried
No abstract text is available yet for this article.
November 8, 2016: Molecular Psychiatry
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