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Translational Psychiatry

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https://www.readbyqxmd.com/read/28534875/dose-dependent-social-cognitive-effects-of-intranasal-oxytocin-delivered-with-novel-breath-powered-device-in-adults-with-autism-spectrum-disorder-a-randomized-placebo-controlled-double-blind-crossover-trial
#1
D S Quintana, L T Westlye, S Hope, T Nærland, T Elvsåshagen, E Dørum, Ø Rustan, M Valstad, L Rezvaya, H Lishaugen, E Stensønes, S Yaqub, K T Smerud, R A Mahmoud, P G Djupesland, O A Andreassen
The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28534874/shifting-brain-inhibitory-balance-and-connectivity-of-the-prefrontal-cortex-of-adults-with-autism-spectrum-disorder
#2
L A Ajram, J Horder, M A Mendez, A Galanopoulos, L P Brennan, R H Wichers, D M Robertson, C M Murphy, J Zinkstok, G Ivin, M Heasman, D Meek, M D Tricklebank, G J Barker, D J Lythgoe, R A E Edden, S C Williams, D G M Murphy, G M McAlonan
Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28534873/molecular-indicators-of-stress-induced-neuroinflammation-in-a-mouse-model-simulating-features-of-post-traumatic-stress-disorder
#3
S Muhie, A Gautam, N Chakraborty, A Hoke, J Meyerhoff, R Hammamieh, M Jett
A social-stress mouse model was used to simulate features of post-traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5 or 10 consecutive days. Transcriptome changes in brain regions (hippocampus, amygdala, medial prefrontal cortex and hemibrain), blood and spleen as well as epigenome changes in the hemibrain were assayed after 1- and 10-day intervals following the 5-day trauma or after 1- and 42-day intervals following the 10-day trauma...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509906/therapeutic-efficacy-of-atypical-antipsychotic-drugs-by-targeting-multiple-stress-related-metabolic-pathways
#4
H L Cai, P Jiang, Q Y Tan, R L Dang, M M Tang, Y Xue, Y Deng, B K Zhang, P F Fang, P Xu, D X Xiang, H D Li, J K Yao
Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509905/crowdsourced-validation-of-a-machine-learning-classification-system-for-autism-and-adhd
#5
M Duda, N Haber, J Daniels, D P Wall
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) together affect >10% of the children in the United States, but considerable behavioral overlaps between the two disorders can often complicate differential diagnosis. Currently, there is no screening test designed to differentiate between the two disorders, and with waiting times from initial suspicion to diagnosis upwards of a year, methods to quickly and accurately assess risk for these and other developmental disorders are desperately needed...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509904/immunological-effects-of-behavioral-activation-with-exercise-in-major-depression-an-exploratory-randomized-controlled-trial
#6
F Euteneuer, K Dannehl, A Del Rey, H Engler, M Schedlowski, W Rief
Major depression (MD) is associated with peripheral inflammation and increased cardiovascular risk. Regular physical exercise can have anti-inflammatory effects. The present study examined whether behavioral activation with exercise affects inflammatory processes in MD. Ninety-eight patients with MD were randomly assigned to cognitive-behavioral therapy (CBT) emphasizing exercise during behavioral activation (CBT-E), CBT with pleasurable low-energy activities as an active control condition (CBT-C) or a passive waiting list control group (WL)...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509903/gray-matter-anomalies-in-pedophiles-with-and-without-a-history-of-child-sexual-offending
#7
B Schiffer, T Amelung, A Pohl, C Kaergel, G Tenbergen, H Gerwinn, S Mohnke, C Massau, W Matthias, S Weiß, V Marr, K M Beier, M Walter, J Ponseti, T H C Krüger, K Schiltz, H Walter
Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509902/a-latent-genetic-subtype-of-major-depression-identified-by-whole-exome-genotyping-data-in-a-mexican-american-cohort
#8
C Yu, M Arcos-Burgos, J Licinio, M-L Wong
Identifying data-driven subtypes of major depressive disorder (MDD) is an important topic of psychiatric research. Currently, MDD subtypes are based on clinically defined depression symptom patterns. Although a few data-driven attempts have been made to identify more homogenous subgroups within MDD, other studies have not focused on using human genetic data for MDD subtyping. Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data from MDD cases and controls using Hamming distance and cluster analysis...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509901/a-continuum-of-genetic-liability-for-minor-and-major-depression
#9
E C Corfield, Y Yang, N G Martin, D R Nyholt
The recent success of a large genome-wide association (GWA) study-analysing 130 620 major depression cases and 347 620 controls-in identifying the first single-nucleotide polymorphism (SNP) loci robustly associated with major depression in Europeans confirms that immense sample sizes are required to identify risk loci for depression. Given the phenotypic similarity between major depressive disorder (MDD) and the less severe minor depressive disorder (MiDD), we hypothesised that broadening the case definition to include MiDD may be an efficient approach to increase sample sizes in GWA studies of depression...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28509900/altered-expression-of-bdnf-bdnf-pro-peptide-and-their-precursor-probdnf-in-brain-and-liver-tissues-from-psychiatric-disorders-rethinking-the-brain-liver-axis
#10
B Yang, Q Ren, J-C Zhang, Q-X Chen, K Hashimoto
Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF and BDNF pro-peptide in the parietal cortex, cerebellum, liver and spleen from control, major depressive disorder (MDD), schizophrenia (SZ) and bipolar disorder (BD) groups...
May 16, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485734/the-effect-of-crack-cocaine-addiction-and-age-on-the-microstructure-and-morphology-of-the-human-striatum-and-thalamus-using-shape-analysis-and-fast-diffusion-kurtosis-imaging
#11
E A Garza-Villarreal, M M Chakravarty, B Hansen, S F Eskildsen, G A Devenyi, D Castillo-Padilla, T Balducci, E Reyes-Zamorano, S N Jespersen, P Perez-Palacios, R Patel, J J Gonzalez-Olvera
The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls (HCs), while investigating the effect of age and years of cocaine consumption...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485733/maternal-immune-activation-results-in-complex-microglial-transcriptome-signature-in-the-adult-offspring-that-is-reversed-by-minocycline-treatment
#12
D Mattei, A Ivanov, C Ferrai, P Jordan, D Guneykaya, A Buonfiglioli, W Schaafsma, P Przanowski, W Deuther-Conrad, P Brust, S Hesse, M Patt, O Sabri, T L Ross, B J L Eggen, E W G M Boddeke, B Kaminska, D Beule, A Pombo, H Kettenmann, S A Wolf
Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485732/pdxdc1-modulates-prepulse-inhibition-of-acoustic-startle-in-the-mouse
#13
L A Feldcamp, P C Boutros, R Raymond, P J Fletcher, J N Nobrega, A H C Wong
Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic prepulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485731/differential-antibody-responses-to-gliadin-derived-indigestible-peptides-in-patients-with-schizophrenia
#14
R T McLean, P Wilson, D St Clair, C J Mustard, J Wei
Gluten consumption has previously been implicated in the development of schizophrenia while an immunological link between gluten and schizophrenia was established by the detection of circulating antibodies against gliadin, a major component of wheat gluten. Several studies have reported an increase in circulating antibodies against native gliadin molecules that are unlikely to survive degradation in the digestive system. In this study, therefore, we measured plasma immunoglobulin G (IgG) and IgA antibodies against indigestible gliadin-derived peptide antigens using an in-house enzyme-linked immunosorbent assay (ELISA) among 169 patients with schizophrenia and 236 control subjects...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485730/altered-neuroinflammatory-arachidonic-acid-cascade-and-synaptic-markers-in-postmortem-alzheimer-s-disease-brain
#15
J S Rao, S I Rapoport, H-W Kim
No abstract text is available yet for this article.
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485729/altered-expression-of-histamine-signaling-genes-in-autism-spectrum-disorder
#16
C Wright, J H Shin, A Rajpurohit, A Deep-Soboslay, L Collado-Torres, N J Brandon, T M Hyde, J E Kleinman, A E Jaffe, A J Cross, D R Weinberger
The histaminergic system (HS) has a critical role in cognition, sleep and other behaviors. Although not well studied in autism spectrum disorder (ASD), the HS is implicated in many neurological disorders, some of which share comorbidity with ASD, including Tourette syndrome (TS). Preliminary studies suggest that antagonism of histamine receptors 1-3 reduces symptoms and specific behaviors in ASD patients and relevant animal models. In addition, the HS mediates neuroinflammation, which may be heightened in ASD...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485728/adenosine-a2a-receptor-inactivation-alleviates-early-onset-cognitive-dysfunction-after-traumatic-brain-injury-involving-an-inhibition-of-tau-hyperphosphorylation
#17
Z-A Zhao, Y Zhao, Y-L Ning, N Yang, Y Peng, P Li, X-Y Chen, D Liu, H Wang, X Chen, W Bai, J-F Chen, Y-G Zhou
Tau is a microtubule-associated protein, and the oligomeric and hyperphosphorylated forms of tau are increased significantly after neurotrauma and considered important factors in mediating cognitive dysfunction. Blockade of adenosine A2A receptors, either by caffeine or gene knockout (KO), alleviates cognitive dysfunction after traumatic brain injury (TBI). We postulated that A2AR activation exacerbates cognitive impairment via promoting tau hyperphosphorylation. Using a mouse model of moderate controlled cortical impact, we showed that TBI induced hyperphosphorylated tau (p-tau) in the hippocampal dentate gyrus and spatial memory deficiency in the Morris water maze test at 7 days and 4 weeks after TBI...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485727/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#18
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
No abstract text is available yet for this article.
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#19
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28485725/sensory-integration-deficits-support-a-dimensional-view-of-psychosis-and-are-not-limited-to-schizophrenia
#20
O Carter, D Bennett, T Nash, S Arnold, L Brown, R Y Cai, Z Allan, A Dluzniak, K McAnally, D Burr, S Sundram
Visual dysfunction is commonplace in schizophrenia and occurs alongside cognitive, psychotic and affective symptoms of the disorder. Psychophysical evidence suggests that this dysfunction results from impairments in the integration of low-level neural signals into complex cortical representations, which may also be associated with symptom formation. Despite the symptoms of schizophrenia occurring in a range of disorders, the integration deficit has not been tested in broader patient populations. Moreover, it remains unclear whether such deficits generalize across other sensory modalities...
May 9, 2017: Translational Psychiatry
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