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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28894304/quantification-of-brain-cholinergic-denervation-in-alzheimer-s-disease-using-pet-imaging-with-18-f-feobv
#1
M Aghourian, C Legault-Denis, J-P Soucy, P Rosa-Neto, S Gauthier, A Kostikov, P Gravel, M-A Bédard
(18)F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894302/g%C3%AE-%C3%AE-subunit-activation-promotes-dopamine-efflux-through-the-dopamine-transporter
#2
J Garcia-Olivares, T Baust, S Harris, P Hamilton, A Galli, S G Amara, G E Torres
The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants-like cocaine and amphetamine-and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#3
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894300/striatal-dopamine-d1-type-receptor-availability-no-difference-from-control-but-association-with-cortical-thickness-in-methamphetamine-users
#4
K Okita, A M Morales, A C Dean, M C Johnson, V Lu, J Farahi, M A Mandelkern, E D London
Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894299/dhea-inhibits-acute-microglia-mediated-inflammation-through-activation-of-the-trka-akt1-2-creb-jmjd3-pathway
#5
V I Alexaki, G Fodelianaki, A Neuwirth, C Mund, A Kourgiantaki, E Ieronimaki, K Lyroni, M Troullinaki, C Fujii, W Kanczkowski, A Ziogas, M Peitzsch, S Grossklaus, B Sönnichsen, A Gravanis, S R Bornstein, I Charalampopoulos, C Tsatsanis, T Chavakis
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894298/molecular-basis-of-dendritic-atrophy-and-activity-in-stress-susceptibility
#6
T C Francis, R Chandra, A Gaynor, P Konkalmatt, S R Metzbower, B Evans, M Engeln, T A Blanpied, M K Lobo
Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894297/the-pnkd-gene-is-associated-with-tourette-disorder-or-tic-disorder-in-a-multiplex-family
#7
N Sun, C Nasello, L Deng, N Wang, Y Zhang, Z Xu, Z Song, K Kwan, R A King, Z P Pang, J Xing, G A Heiman, J A Tischfield
Tourette Disorder (TD) is a childhood-onset neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. The genetic architecture of TD is believed to be complex and heterogeneous. Nevertheless, DNA sequence variants co-segregating with TD phenotypes within multiplex families have been identified. This report examines whole exomes of affected and unaffected individuals in a multiplex TD family to discover genes involved in the TD etiology. We performed whole exome sequencing on six out of nine members in a three-generation TD multiplex family...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28892069/reduction-of-plasma-glutathione-in-psychosis-associated-with-schizophrenia-and-bipolar-disorder-in-translational-psychiatry
#8
L G Nucifora, T Tanaka, L N Hayes, M Kim, B J Lee, T Matsuda, F C Nucifora, T Sedlak, R Mojtabai, W Eaton, A Sawa
The establishment of mechanism-driven peripheral markers is important for translational psychiatry. Many groups, including ours, have addressed molecular alterations in peripheral tissues in association with symptomatic changes in major illnesses. Oxidative stress is implicated in the pathophysiology of schizophrenia (SZ) and bipolar disorder (BP) through studies of patient peripheral tissues and animal models. Although the relationship between peripheral changes and brain pathology remain elusive, oxidative stress may bridge such translational efforts...
August 22, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28886009/tau-mediated-iron-export-prevents-ferroptotic-damage-after-ischemic-stroke
#9
Q-Z Tuo, P Lei, K A Jackman, X-L Li, H Xiong, X-L Li, Z-Y Liuyang, L Roisman, S-T Zhang, S Ayton, Q Wang, P J Crouch, K Ganio, X-C Wang, L Pei, P A Adlard, Y-M Lu, R Cappai, J-Z Wang, R Liu, A I Bush
Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors...
September 8, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28877513/predicting-functional-neuroanatomical-maps-from-fusing-brain-networks-with-genetic-information
#10
REVIEW
Florian Ganglberger, Joanna Kaczanowska, Josef M Penninger, Andreas Hess, Katja Bühler, Wulf Haubensak
Functional neuroanatomical maps provide a mesoscale reference framework for studies from molecular to systems neuroscience and psychiatry. The underlying structure-function relationships are typically derived from functional manipulations or imaging approaches. Although highly informative, these are experimentally costly. The increasing amount of publicly available brain and genetic data offers a rich source that could be mined to address this problem computationally. Here, we developed an algorithm that fuses gene expression and connectivity data with functional genetic meta data and exploits cumulative effects to derive neuroanatomical maps related to multi-genic functions...
September 3, 2017: NeuroImage
https://www.readbyqxmd.com/read/28860775/a-case-of-paroxysmal-kinesigenic-dyskinesia-which-exhibited-the-phenotype-of-anxiety-disorder
#11
Yasuto Kunii, Nozomu Matsuda, Hirooki Yabe
BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is a rare heritable neurologic disorder characterized by attacks of involuntary movement induced by sudden voluntary movements. No previous reports have described cases showing comorbidity with psychiatric disease or symptoms. In this case, we showed a patient with PKD who exhibited several manifestations of anxiety disorder. CASE: A 35-year-old Japanese man with PKD had been maintained on carbamazepine since he was 16 years of age without any attacks...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28827761/copy-number-elevation-of-22q11-2-genes-arrests-the-developmental-maturation-of-working-memory-capacity-and-adult-hippocampal-neurogenesis
#12
S Boku, T Izumi, S Abe, T Takahashi, A Nishi, H Nomaru, Y Naka, G Kang, M Nagashima, A Hishimoto, S Enomoto, G Duran-Torres, K Tanigaki, J Zhang, K Ye, S Kato, P T Männistö, K Kobayashi, N Hiroi
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11...
August 22, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#13
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
#14
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
#15
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...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28805182/human-induced-pluripotent-stem-cells-as-a-research-tool-in-alzheimer-s-disease
#16
J P Robbins, J Price
Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents...
August 14, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28795915/where-teachers-are-few-documenting-available-faculty-in-five-tanzanian-medical-schools
#17
Charles A Mkony, Ephata E Kaaya, Alex J Goodell, Sarah B Macfarlane
Background Faced with one of the lowest physician-to-population ratios in the world, the Government of Tanzania is urging its medical schools to train more physicians. The annual number of medical students admitted across the country rose from 55 in the 1990s to 1,680 approved places for the 2015/16 academic year. These escalating numbers strain existing faculty. Objective To describe the availability of faculty in medical schools in Tanzania. Design We identified faculty lists published on the Internet by five Tanzanian medical schools for the 2011/12 academic year and analyzed the appointment status, rank, discipline, and qualifications of faculty members...
December 2016: Global Health Action
https://www.readbyqxmd.com/read/28761083/revealing-the-complex-genetic-architecture-of-obsessive-compulsive-disorder-using-meta-analysis
#18
(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
#19
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
#20
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
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