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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#1
A Alachkar, L Wang, R Yoshimura, A R Hamzeh, Z Wang, N Sanathara, S M Lee, X Xu, G W Abbott, O Civelli
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809399/evidence-for-newly-generated-interneurons-in-the-basolateral-amygdala-of-adult-mice
#2
D J Jhaveri, A Tedoldi, S Hunt, R Sullivan, N R Watts, J M Power, P F Bartlett, P Sah
New neurons are continually generated from the resident populations of precursor cells in selective niches of the adult mammalian brain such as the hippocampal dentate gyrus and the olfactory bulb. However, whether such cells are present in the adult amygdala, and their neurogenic capacity, is not known. Using the neurosphere assay, we demonstrate that a small number of precursor cells, the majority of which express Achaete-scute complex homolog 1 (Ascl1), are present in the basolateral amygdala (BLA) of the adult mouse...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#3
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28785111/multi-polygenic-score-approach-to-trait-prediction
#4
E Krapohl, H Patel, S Newhouse, C J Curtis, S von Stumm, P S Dale, D Zabaneh, G Breen, P F O'Reilly, R Plomin
A primary goal of polygenic scores, which aggregate the effects of thousands of trait-associated DNA variants discovered in genome-wide association studies (GWASs), is to estimate individual-specific genetic propensities and predict outcomes. This is typically achieved using a single polygenic score, but here we use a multi-polygenic score (MPS) approach to increase predictive power by exploiting the joint power of multiple discovery GWASs, without assumptions about the relationships among predictors. We used summary statistics of 81 well-powered GWASs of cognitive, medical and anthropometric traits to predict three core developmental outcomes in our independent target sample: educational achievement, body mass index (BMI) and general cognitive ability...
August 8, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28785110/impact-of-video-games-on-plasticity-of-the-hippocampus
#5
G L West, K Konishi, M Diarra, J Benady-Chorney, B L Drisdelle, L Dahmani, D J Sodums, F Lepore, P Jolicoeur, V D Bohbot
The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in participants using non-spatial memory strategies. Conversely, participants who use hippocampus-dependent spatial strategies showed increased grey matter in the hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the hippocampus or the functionally connected entorhinal cortex...
August 8, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28785109/the-genealogy-of-major-depression-symptoms-and-signs-of-melancholia-from-1880-to-1900
#6
K S Kendler
How deep are the historical roots of our concept of major depression (MD)? I showed previously that psychiatric textbooks published in 1900-1960 commonly described 18 characteristic depressive symptoms/signs that substantially but incompletely overlapped with the current DSM (Diagnostic and Statistical Manual of Mental Disorders) MD criteria. I here expand that inquiry to the key years of 1880-1900 during which our major diagnostic categories of manic-depressive illness (MDI) and dementia praecox were developed...
August 8, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761083/revealing-the-complex-genetic-architecture-of-obsessive-compulsive-disorder-using-meta-analysis
#7
(no author information available yet)
Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761082/selective-activation-of-parvalbumin-interneurons-prevents-stress-induced-synapse-loss-and-perceptual-defects
#8
C-C Chen, J Lu, R Yang, J B Ding, Y Zuo
Stress, a prevalent experience in modern society, is a major risk factor for many psychiatric disorders. Although sensorimotor abnormalities are often present in these disorders, little is known about how stress affects the sensory cortex. Combining behavioral analyses with in vivo synaptic imaging, we show that stressful experiences lead to progressive, clustered loss of dendritic spines along the apical dendrites of layer (L) 5 pyramidal neurons (PNs) in the mouse barrel cortex, and such spine loss closely associates with deteriorated performance in a whisker-dependent texture discrimination task...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761081/a-neurogenetic-model-for-the-study-of-schizophrenia-spectrum-disorders-the-international-22q11-2-deletion-syndrome-brain-behavior-consortium
#9
R E Gur, A S Bassett, D M McDonald-McGinn, C E Bearden, E Chow, B S Emanuel, M Owen, A Swillen, M Van den Bree, J Vermeesch, J A S Vorstman, S Warren, T Lehner, B Morrow
Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761080/serotonin-inputs-to-the-dorsal-bnst-modulate-anxiety-in-a-5-ht1a-receptor-dependent-manner
#10
A L Garcia-Garcia, S Canetta, J M Stujenske, N S Burghardt, M S Ansorge, A Dranovsky, E D Leonardo
Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761079/alterations-in-resting-state-connectivity-along-the-autism-trait-continuum-a-twin-study
#11
J Neufeld, R Kuja-Halkola, K Mevel, É Cauvet, P Fransson, S Bölte
Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28761078/the-complement-system-a-gateway-to-gene-environment-interactions-in-schizophrenia-pathogenesis
#12
V L Nimgaonkar, K M Prasad, K V Chowdari, E G Severance, R H Yolken
The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens...
August 1, 2017: Molecular Psychiatry
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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