Biological psychiatry
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Biological psychiatry · Jul 2016
Neural Connectivity Evidence for a Categorical-Dimensional Hybrid Model of Autism Spectrum Disorder.
Autism spectrum disorder (ASD) encompasses a complex manifestation of symptoms that include deficits in social interaction and repetitive or stereotyped interests and behaviors. In keeping with the increasing recognition of the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate the neural mechanisms of ASD symptoms based on the functional connectivity of four known neural networks (i.e., default mode network, dorsal attention network, salience network, and executive control network). ⋯ Our findings support a hybrid model for ASD characterization that includes a combination of categorical and dimensional brain mechanisms and provide a novel understanding of the neural underpinnings of ASD.
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Biological psychiatry · Jul 2016
Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor.
The mechanisms underlying stress-induced inflammation that contribute to major depressive disorder are unknown. We examine the role of the adenosine triphosphate (ATP)/purinergic type 2X7 receptor (P2X7R) pathway and the NLRP3 (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) inflammasome in interleukin (IL)-1β and depressive behavioral responses to stress. ⋯ These findings demonstrate that psychological "stress" is sensed by the innate immune system in the brain via the ATP/P2X7R-NLRP3 inflammasome cascade, and they identify novel therapeutic targets for the treatment of stress-related mood disorders and comorbid illnesses.
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Biological psychiatry · Jun 2016
Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders.
There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. ⋯ Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment.
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Biological psychiatry · Jun 2016
Mice Lacking GPR88 Show Motor Deficit, Improved Spatial Learning, and Low Anxiety Reversed by Delta Opioid Antagonist.
GPR88 is an orphan G protein coupled receptor highly enriched in the striatum, and previous studies have focused on GPR88 function in striatal physiology. The receptor is also expressed in other brain areas, and here we examined whether GPR88 function extends beyond striatal-mediated responses. ⋯ We demonstrate that GPR88 is implicated in a large repertoire of behavioral responses that engage motor activity, spatial learning, and emotional processing. Our data also reveal functional antagonism between GPR88 and DOR activities in vivo. The therapeutic potential of GPR88 therefore extends to cognitive and anxiety disorders, possibly in interaction with other receptor systems.
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Biological psychiatry · May 2016
Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention. ⋯ Data from this largest cohort of anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic resonance imaging demonstrate that structural hippocampal damage and associated memory deficits are important long-term sequelae of the encephalitis. Correlation with disease duration and severity highlights the need for rapid diagnosis and adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced imaging protocols may allow a more detailed analysis of structural damage to assess disease progression in clinical routine examinations and for therapy evaluation in prospective trials.