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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28416813/brain-derived-neurotrophic-factor-val-66-met-genotype-and-ovarian-steroids-interactively-modulate-working-memory-related-hippocampal-function-in-women-a-multimodal-neuroimaging-study
#1
S-M Wei, E B Baller, P D Kohn, J S Kippenhan, B Kolachana, S J Soldin, D R Rubinow, P J Schmidt, K F Berman
Preclinical evidence suggests that the actions of ovarian steroid hormones and brain-derived neurotrophic factor (BDNF) are highly convergent on brain function. Studies in humanized mice document an interaction between estrus cycle-related changes in estradiol secretion and BDNF Val(66)Met genotype on measures of hippocampal function and anxiety-like behavior. We believe our multimodal imaging data provide the first demonstration in women that the effects of the BDNF Val/Met polymorphism on hippocampal function are selectively modulated by estradiol...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416812/a-new-locus-regulating-micall2-expression-was-identified-for-association-with-executive-inhibition-in-children-with-attention-deficit-hyperactivity-disorder
#2
L Yang, S Chang, Q Lu, Y Zhang, Z Wu, X Sun, Q Cao, Y Qian, T Jia, B Xu, Q Duan, Y Li, K Zhang, G Schumann, D Liu, J Wang, Y Wang, L Lu
Impaired executive inhibition is a core deficit of attention deficit hyperactivity disorder (ADHD), which is a common childhood-onset psychiatric disorder with high heritability. In this study, we performed a two-stage genome-wide association study of executive inhibition in ADHD in Han Chinese. We used the Stroop color-word interference test to evaluate executive inhibition. After quality control, 780 samples with phenotype and covariate data were included in the discovery stage, whereas 922 samples were included in the replication stage...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416811/gene-deficiency-and-pharmacological-inhibition-of-caspase-1-confers-resilience-to-chronic-social-defeat-stress-via-regulating-the-stability-of-surface-ampars
#3
M-X Li, H-L Zheng, Y Luo, J-G He, W Wang, J Han, L Zhang, X Wang, L Ni, H-Y Zhou, Z-L Hu, P-F Wu, Y Jin, L-H Long, H Zhang, G Hu, J-G Chen, F Wang
Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1(-/-) knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416810/the-joint-impact-of-cognitive-performance-in-adolescence-and-familial-cognitive-aptitude-on-risk-for-major-psychiatric-disorders-a-delineation-of-four-potential-pathways-to-illness
#4
K S Kendler, H Ohlsson, R S E Keefe, K Sundquist, J Sundquist
How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in siblings and cousins, and educational attainment in parents-on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA-that is a level of SA lower than would be predicted from the FCA...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416809/perisomatic-changes-in-h-channels-regulate-depressive-behaviors-following-chronic-unpredictable-stress
#5
C S Kim, D H Brager, D Johnston
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416808/ptchd1-deficiency-induces-excitatory-synaptic-and-cognitive-dysfunctions-in-mouse
#6
D C Ung, G Iacono, H Méziane, E Blanchard, M-A Papon, M Selten, J-R van Rhijn, R Montjean, J Rucci, S Martin, A Fleet, M-C Birling, S Marouillat, R Roepman, M Selloum, A Lux, R-A Thépault, P Hamel, K Mittal, J B Vincent, O Dorseuil, H G Stunnenberg, P Billuart, N Nadif Kasri, Y Hérault, F Laumonnier
Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416807/a-simplified-protocol-for-differentiation-of-electrophysiologically-mature-neuronal-networks-from-human-induced-pluripotent-stem-cells
#7
N Gunhanlar, G Shpak, M van der Kroeg, L A Gouty-Colomer, S T Munshi, B Lendemeijer, M Ghazvini, C Dupont, W J G Hoogendijk, J Gribnau, F M S de Vrij, S A Kushner
Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416806/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#8
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
No abstract text is available yet for this article.
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397842/structural-alterations-within-cerebellar-circuitry-are-associated-with-general-liability-for-common-mental-disorders
#9
A L Romer, A R Knodt, R Houts, B D Brigidi, T E Moffitt, A Caspi, A R Hariri
Accumulating mental-health research encourages a shift in focus toward transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology-sometimes called the 'p factor'- that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the 'p factor' contributes to risk...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397841/ketamine-induced-reduction-in-mglur5-availability-is-associated-with-an-antidepressant-response-an-11-c-abp688-and-pet-imaging-study-in-depression
#10
I Esterlis, N DellaGioia, R H Pietrzak, D Matuskey, N Nabulsi, C G Abdallah, J Yang, C Pittenger, G Sanacora, J H Krystal, R V Parsey, R E Carson, C DeLorenzo
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [(11)C]ABP688 positron emission tomography (PET) scans on the same day-before and during intravenous ketamine administration-and a third scan 1 day later...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397840/neuronal-plasticity-and-neurotrophic-factors-in-drug-responses
#11
E Castrén, H Antila
Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397839/a-connectomic-approach-for-subcallosal-cingulate-deep-brain-stimulation-surgery-prospective-targeting-in-treatment-resistant-depression
#12
P Riva-Posse, K S Choi, P E Holtzheimer, A L Crowell, S J Garlow, J K Rajendra, C C McIntyre, R E Gross, H S Mayberg
Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography 'connectome blueprint' to plan surgical targeting in 11 participants with treatment-resistant depression...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397838/mapping-autosomal-recessive-intellectual-disability-combined-microarray-and-exome-sequencing-identifies-26-novel-candidate-genes-in-192-consanguineous-families
#13
R Harripaul, N Vasli, A Mikhailov, M A Rafiq, K Mittal, C Windpassinger, T I Sheikh, A Noor, H Mahmood, S Downey, M Johnson, K Vleuten, L Bell, M Ilyas, F S Khan, V Khan, M Moradi, M Ayaz, F Naeem, A Heidari, I Ahmed, S Ghadami, Z Agha, S Zeinali, R Qamar, H Mozhdehipanah, P John, A Mir, M Ansar, L French, M Ayub, J B Vincent
Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397837/the-nucleus-reuniens-a-key-node-in-the-neurocircuitry-of-stress-and-depression
#14
V Kafetzopoulos, N Kokras, I Sotiropoulos, J F Oliveira, H Leite-Almeida, A Vasalou, V M Sardinha, Z Papadopoulou-Daifoti, O F X Almeida, K Antoniou, N Sousa, C Dalla
The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28397836/efhd2-swiprosin-1-is-a-common-genetic-determinator-for-sensation-seeking-low-anxiety-and-alcohol-addiction
#15
D Mielenz, M Reichel, T Jia, E B Quinlan, T Stöckl, M Mettang, D Zilske, E Kirmizi-Alsan, P Schönberger, M Praetner, S E Huber, D Amato, M Schwarz, P Purohit, S Brachs, J Spranger, A Hess, C Büttner, A B Ekici, F Perez-Branguli, B Winner, V Rauschenberger, T Banaschewski, A L W Bokde, C Büchel, P J Conrod, S Desrivières, H Flor, V Frouin, J Gallinat, H Garavan, P Gowland, A Heinz, J-L Martinot, H Lemaitre, F Nees, T Paus, M N Smolka, A Schambony, T Bäuerle, V Eulenburg, C Alzheimer, A Lourdusamy, G Schumann, C P Müller
In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype...
April 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373692/a-missense-mutation-in-katnal1-underlies-behavioural-neurological-and-ciliary-anomalies
#16
G Banks, G Lassi, A Hoerder-Suabedissen, F Tinarelli, M M Simon, A Wilcox, P Lau, T N Lawson, S Johnson, A Rutman, M Sweeting, J E Chesham, A R Barnard, N Horner, H Westerberg, L B Smith, Z Molnár, M H Hastings, R A Hirst, V Tucci, P M Nolan
Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373691/blocking-human-fear-memory-with-the-matrix-metalloproteinase-inhibitor-doxycycline
#17
D R Bach, A Tzovara, J Vunder
Learning to predict threat is a fundamental ability of many biological organisms, and a laboratory model for anxiety disorders. Interfering with such memories in humans would be of high clinical relevance. On the basis of studies in cell cultures and slice preparations, it is hypothesised that synaptic remodelling required for threat learning involves the extracellular enzyme matrix metalloproteinase (MMP) 9. However, in vivo evidence for this proposal is lacking. Here we investigate human Pavlovian fear conditioning under the blood-brain barrier crossing MMP inhibitor doxycyline in a pre-registered, randomised, double-blind, placebo-controlled trial...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373690/a-paternal-methyl-donor-rich-diet-altered-cognitive-and-neural-functions-in-offspring-mice
#18
D P Ryan, K S Henzel, B L Pearson, M E Siwek, A Papazoglou, L Guo, K Paesler, M Yu, R Müller, K Xie, S Schröder, L Becker, L Garrett, S M Hölter, F Neff, I Rácz, B Rathkolb, J Rozman, G Ehninger, M Klingenspor, T Klopstock, E Wolf, W Wurst, A Zimmer, H Fuchs, V Gailus-Durner, M Hrabě de Angelis, K Sidiropoulou, M Weiergräber, Y Zhou, D Ehninger
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373689/collaborative-meta-analysis-finds-no-evidence-of-a-strong-interaction-between-stress-and-5-httlpr-genotype-contributing-to-the-development-of-depression
#19
R C Culverhouse, N L Saccone, A C Horton, Y Ma, K J Anstey, T Banaschewski, M Burmeister, S Cohen-Woods, B Etain, H L Fisher, N Goldman, S Guillaume, J Horwood, G Juhasz, K J Lester, L Mandelli, C M Middeldorp, E Olié, S Villafuerte, T M Air, R Araya, L Bowes, R Burns, E M Byrne, C Coffey, W L Coventry, K A B Gawronski, D Glei, A Hatzimanolis, J-J Hottenga, I Jaussent, C Jawahar, C Jennen-Steinmetz, J R Kramer, M Lajnef, K Little, H M Zu Schwabedissen, M Nauck, E Nederhof, P Petschner, W J Peyrot, C Schwahn, G Sinnamon, D Stacey, Y Tian, C Toben, S Van der Auwera, N Wainwright, J-C Wang, G Willemsen, I M Anderson, V Arolt, C Åslund, G Bagdy, B T Baune, F Bellivier, D I Boomsma, P Courtet, U Dannlowski, E J C de Geus, J F W Deakin, S Easteal, T Eley, D M Fergusson, A M Goate, X Gonda, H J Grabe, C Holzman, E O Johnson, M Kennedy, M Laucht, N G Martin, M R Munafò, K W Nilsson, A J Oldehinkel, C A Olsson, J Ormel, C Otte, G C Patton, B W J H Penninx, K Ritchie, M Sarchiapone, J M Scheid, A Serretti, J H Smit, N C Stefanis, P G Surtees, H Völzke, M Weinstein, M Whooley, J I Nurnberger, N Breslau, L J Bierut
The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373688/microglial-recruitment-of-il-1%C3%AE-producing-monocytes-to-brain-endothelium-causes-stress-induced-anxiety
#20
D B McKim, M D Weber, A Niraula, C M Sawicki, X Liu, B L Jarrett, K Ramirez-Chan, Y Wang, R M Roeth, A D Sucaldito, C G Sobol, N Quan, J F Sheridan, J P Godbout
Psychosocial stress contributes to the development of anxiety and depression. Recent clinical studies have reported increased inflammatory leukocytes in circulation of individuals with stress-related psychiatric disorders. Parallel to this, our work in mice shows that social stress causes release of inflammatory monocytes into circulation. In addition, social stress caused the development of prolonged anxiety that was dependent on inflammatory monocytes in the brain. Therefore, we hypothesize that chronic stress drives the production of inflammatory monocytes that are actively recruited to the brain by microglia, and these monocytes augment neuroinflammatory signaling and prolong anxiety...
April 4, 2017: Molecular Psychiatry
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