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Molecular Psychiatry

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https://www.readbyqxmd.com/read/29133955/chemokines-in-depression-in-health-and-in-inflammatory-illness-a-systematic-review-and-meta-analysis
#1
REVIEW
S P Leighton, L Nerurkar, R Krishnadas, C Johnman, G J Graham, J Cavanagh
Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participants with physical illness for subgroup analysis, and excluded participants with comorbid psychiatric diagnoses...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133954/exogenous-ghrelin-administration-increases-alcohol-self-administration-and-modulates-brain-functional-activity-in-heavy-drinking-alcohol-dependent-individuals
#2
M Farokhnia, E N Grodin, M R Lee, E N Oot, A N Blackburn, B L Stangl, M L Schwandt, L A Farinelli, R Momenan, V A Ramchandani, L Leggio
Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133952/engaging-homeostatic-plasticity-to-treat-depression
#3
E R Workman, F Niere, K F Raab-Graham
Major depressive disorder (MDD) is a complex and heterogeneous mood disorder, making it difficult to develop a generalized, pharmacological therapy that is effective for all who suffer from MDD. Through the fortuitous discovery of N-methyl-D-aspartate receptor (NMDAR) antagonists as effective antidepressants, we have gained key insights into how antidepressant effects can be produced at the circuit and molecular levels. NMDAR antagonists act as rapid-acting antidepressants such that relief from depressive symptoms occurs within hours of a single injection...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133950/treating-a-novel-plasticity-defect-rescues-episodic-memory-in-fragile-x-model-mice
#4
W Wang, B M Cox, Y Jia, A A Le, C D Cox, K M Jung, B Hou, D Piomelli, C M Gall, Gary Lynch
Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133949/a-total-population-multigenerational-family-clustering-study-of-autoimmune-diseases-in-obsessive-compulsive-disorder-and-tourette-s-chronic-tic-disorders
#5
D Mataix-Cols, E Frans, A Pérez-Vigil, R Kuja-Halkola, C Gromark, K Isomura, L Fernández de la Cruz, E Serlachius, J F Leckman, J J Crowley, C Rück, C Almqvist, P Lichtenstein, H Larsson
The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133948/increased-hippocampal-tail-volume-predicts-depression-status-and-remission-to-anti-depressant-medications-in-major-depression
#6
J J Maller, K Broadhouse, A J Rush, E Gordon, S Koslow, S M Grieve
Studies of patients with major depressive disorder (MDD) have consistently reported reduced hippocampal volumes; however, the exact pattern of these volume changes in specific anatomical subfields and their functional significance is unclear. We sought to clarify the relationship between hippocampal tail volumes and (i) a diagnosis of MDD, and (ii) clinical remission to anti-depressant medications (ADMs). Outpatients with nonpsychotic MDD (n=202) based on DSM-IV criteria and a 17-item Hamilton Rating Scale for Depression (HRSD17) score ⩾16 underwent pretreatment magnetic resonance imaging as part of the international Study to Predict Optimized Treatment for Depression (iSPOT-D)...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112198/co-aggregation-of-major-psychiatric-disorders-in-individuals-with-first-degree-relatives-with-schizophrenia-a-nationwide-population-based-study
#7
C-M Cheng, W-H Chang, M-H Chen, C-F Tsai, T-P Su, C-T Li, S-J Tsai, J-W Hsu, K-L Huang, W-C Lin, T-J Chen, Y-M Bai
A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112197/association-of-genetic-ancestry-with-striatal-dopamine-d2-d3-receptor-availability
#8
C E Wiers, P C Towb, C A Hodgkinson, P-H Shen, C Freeman, G Miller, E Lindgren, E Shokri-Kojori, Ş B Demiral, S W Kim, D Tomasi, H Sun, G-J Wang, D Goldman, N D Volkow
Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [(11)C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes)...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112196/understanding-the-roles-of-mutations-in-the-amyloid-precursor-protein-in-alzheimer-disease
#9
REVIEW
S Hunter, C Brayne
Many models of disease progression in Alzheimer's disease (AD) have been proposed to help guide experimental design and aid the interpretation of results. Models focussing on the genetic evidence include the amyloid cascade (ACH) and presenilin (PSH) hypotheses and the amyloid precursor protein (APP) matrix approach (AMA), of which the ACH has held a dominant position for over two decades. However, the ACH has never been fully accepted and has not yet delivered on its therapeutic promise. We review the ACH, PSH and AMA in relation to levels of APP proteolytic fragments reported from AD-associated mutations in APP...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112195/face-and-predictive-validity-of-the-clock%C3%AE-19-mouse-as-an-animal-model-for-bipolar-disorder-a-systematic-review
#10
REVIEW
M Kristensen, A A Nierenberg, S D Østergaard
Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112194/genome-wide-association-study-identifies-a-novel-locus-for-cannabis-dependence
#11
A Agrawal, Y-L Chou, C E Carey, D A A Baranger, B Zhang, R Sherva, L Wetherill, M Kapoor, J-C Wang, S Bertelsen, A P Anokhin, V Hesselbrock, J Kramer, M T Lynskey, J L Meyers, J I Nurnberger, J P Rice, J Tischfield, L J Bierut, L Degenhardt, L A Farrer, J Gelernter, A R Hariri, A C Heath, H R Kranzler, P A F Madden, N G Martin, G W Montgomery, B Porjesz, T Wang, J B Whitfield, H J Edenberg, T Foroud, A M Goate, R Bogdan, E C Nelson
Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112193/transcriptome-alterations-of-prefrontal-cortical-parvalbumin-neurons-in-schizophrenia
#12
J F Enwright Iii, Z Huo, D Arion, J P Corradi, G Tseng, D A Lewis
Schizophrenia (SZ) is associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction is manifest as cognitive deficits that appear to arise from disturbances in gamma frequency oscillations. These oscillations are generated in DLPFC layer 3 (L3) via reciprocal connections between pyramidal cells (PCs) and parvalbumin (PV)-containing interneurons. The density of cortical PV neurons is not altered in SZ, but expression levels of several transcripts involved in PV cell function, including PV, are lower in the disease...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112191/identifying-specific-prefrontal-neurons-that-contribute-to-autism-associated-abnormalities-in-physiology-and-social-behavior
#13
A C Brumback, I T Ellwood, C Kjaerby, J Iafrati, S Robinson, A T Lee, T Patel, S Nagaraj, F Davatolhagh, V S Sohal
Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29058593/brain-donation-in-psychiatry-results-of-a-dutch-prospective-donor-program-among-psychiatric-cohort-participants
#14
Geertje M de Lange, Marleen Rademaker, Marco P Boks, Saskia J M C Palmen
BACKGROUND: Human brain tissue is crucial to study the molecular and cellular basis of psychiatric disorders. However, the current availability of human brain tissue is inadequate. Therefore, the Netherlands Brain Bank initiated a program in which almost 4.000 participants of 15 large Dutch psychiatric research cohorts were asked to register as prospective brain donors. METHODS: We approached patients with schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, families with a child with autism or Attention Deficit Hyperactivity Disorder, healthy relatives and healthy unrelated controls, either face-to-face or by post...
October 20, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/29038599/widespread-white-matter-microstructural-differences-in-schizophrenia-across-4322-individuals-results-from-the-enigma-schizophrenia-dti-working-group
#15
S Kelly, N Jahanshad, A Zalesky, P Kochunov, I Agartz, C Alloza, O A Andreassen, C Arango, N Banaj, S Bouix, C A Bousman, R M Brouwer, J Bruggemann, J Bustillo, W Cahn, V Calhoun, D Cannon, V Carr, S Catts, J Chen, J-X Chen, X Chen, C Chiapponi, Kl K Cho, V Ciullo, A S Corvin, B Crespo-Facorro, V Cropley, P De Rossi, C M Diaz-Caneja, E W Dickie, S Ehrlich, F-M Fan, J Faskowitz, H Fatouros-Bergman, L Flyckt, J M Ford, J-P Fouche, M Fukunaga, M Gill, D C Glahn, R Gollub, E D Goudzwaard, H Guo, R E Gur, R C Gur, T P Gurholt, R Hashimoto, S N Hatton, F A Henskens, D P Hibar, I B Hickie, L E Hong, J Horacek, F M Howells, H E Hulshoff Pol, C L Hyde, D Isaev, A Jablensky, P R Jansen, J Janssen, E G Jönsson, L A Jung, R S Kahn, Z Kikinis, K Liu, P Klauser, C Knöchel, M Kubicki, J Lagopoulos, C Langen, S Lawrie, R K Lenroot, K O Lim, C Lopez-Jaramillo, A Lyall, V Magnotta, R C W Mandl, D H Mathalon, R W McCarley, S McCarthy-Jones, C McDonald, S McEwen, A McIntosh, T Melicher, R I Mesholam-Gately, P T Michie, B Mowry, B A Mueller, D T Newell, P O'Donnell, V Oertel-Knöchel, L Oestreich, S A Paciga, C Pantelis, O Pasternak, G Pearlson, G R Pellicano, A Pereira, J Pineda Zapata, F Piras, S G Potkin, A Preda, P E Rasser, D R Roalf, R Roiz, A Roos, D Rotenberg, T D Satterthwaite, P Savadjiev, U Schall, R J Scott, M L Seal, L J Seidman, C Shannon Weickert, C D Whelan, M E Shenton, J S Kwon, G Spalletta, F Spaniel, E Sprooten, M Stäblein, D J Stein, S Sundram, Y Tan, S Tan, S Tang, H S Temmingh, L T Westlye, S Tønnesen, D Tordesillas-Gutierrez, N T Doan, J Vaidya, N E M van Haren, C D Vargas, D Vecchio, D Velakoulis, A Voineskos, J Q Voyvodic, Z Wang, P Wan, D Wei, T W Weickert, H Whalley, T White, T J Whitford, J D Wojcik, H Xiang, Z Xie, H Yamamori, F Yang, N Yao, G Zhang, J Zhao, T G M van Erp, J Turner, P M Thompson, G Donohoe
The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies...
October 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29038598/male-specific-deficits-in-natural-reward-learning-in-a-mouse-model-of-neurodevelopmental-disorders
#16
N M Grissom, S E McKee, H Schoch, N Bowman, R Havekes, W T O'Brien, E Mahrt, S Siegel, K Commons, C Portfors, T Nickl-Jockschat, T M Reyes, T Abel
Neurodevelopmental disorders, including autism spectrum disorders, are highly male biased, but the underpinnings of this are unknown. Striatal dysfunction has been strongly implicated in the pathophysiology of neurodevelopmental disorders, raising the question of whether there are sex differences in how the striatum is impacted by genetic risk factors linked to neurodevelopmental disorders. Here we report male-specific deficits in striatal function important to reward learning in a mouse model of 16p11.2 hemideletion, a genetic mutation that is strongly associated with the risk of neurodevelopmental disorders, particularly autism and attention-deficit hyperactivity disorder...
October 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#17
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29019460/auditory-hallucinations-as-translational-psychiatry-evidence-from-magnetic-resonance-imaging
#18
Kenneth Hugdahl
In this invited review article I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway with a focus on the neuronal mechanisms underlying the phenomenology of experiencing "hearing voices". An auditory verbal hallucination, i.e. "hearing a voice", is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations which is called Levels of Explanation (LoE)...
October 11, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28993711/social-impairments-in-autism-spectrum-disorder-are-related-to-maternal-immune-history-profile
#19
S Patel, A Masi, R C Dale, A J O Whitehouse, I Pokorski, G A Alvares, I B Hickie, E Breen, A J Guastella
Maternal immune activation has been highlighted as a factor that might increase the risk and severity of autism spectrum disorder (ASD) in children. Preclinical animal evidence shows that immune activation in mothers during pregnancy causes ASD-like behavioural traits in offspring. To this point, there has been no investigation of whether immune system activation in human mothers during pregnancy is associated with more severe symptoms in children with ASD. In this study, data from an existing ASD cohort (N=220) were analysed to investigate whether immune conditions in the mother were associated with greater severity of autism-related symptoms...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#20
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
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