Biological psychiatry
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Biological psychiatry · Jun 2018
Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula-Tegmental Circuitry and Constrain Reward Seeking.
The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. We identify a noncanonical population of glutamatergic VP neurons that play a unique role in responding to aversive stimuli and constraining inappropriate reward seeking. ⋯ Glutamatergic VP neurons constitute a noncanonical subpopulation of VP neurons. These glutamatergic VP neurons increase activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons and adaptively constrain reward seeking.
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Biological psychiatry · Apr 2018
Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.
Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected. ⋯ Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia.
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Biological psychiatry · Mar 2018
Brain Regions Showing White Matter Loss in Huntington's Disease Are Enriched for Synaptic and Metabolic Genes.
The earliest white matter changes in Huntington's disease are seen before disease onset in the premanifest stage around the striatum, within the corpus callosum, and in posterior white matter tracts. While experimental evidence suggests that these changes may be related to abnormal gene transcription, we lack an understanding of the biological processes driving this regional vulnerability. ⋯ These findings suggest a dual mechanism of white matter vulnerability in Huntington's disease, in which abnormal transcription of synaptic genes and metabolic disturbance not related to transcription may drive white matter loss.
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Biological psychiatry · Feb 2018
ReviewHarnessing Gut Microbes for Mental Health: Getting From Here to There.
There has been an explosion of interest in the study of microorganisms inhabiting the gastrointestinal tract (gut microbiota) and their impact on host health and physiology. Accumulating data suggest that altered communication between gut microbiota and host systems could participate in disorders such as obesity, diabetes mellitus, and autoimmune disorders as well as neuropsychiatric disorders, including autism, anxiety, and major depressive disorders. The conceptual development of the microbiome-gut-brain axis has facilitated understanding of the complex and bidirectional networks between gastrointestinal microbiota and their host, highlighting potential mechanisms through which this environment influences central nervous system physiology. ⋯ However, uncertainty remains regarding the generalizability of controlled animal studies to the more multifaceted pattern of human pathophysiology, especially with regard to the therapeutic potential for neuropsychiatric health. This narrative review summarizes current understanding of gut microbial influence over physiological function, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis. Experimental and clinical data regarding means of therapeutic manipulation of gut microbiota as a novel treatment option for mental health are described, and important knowledge gaps are identified and discussed.
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Biological psychiatry · Nov 2017
Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.
There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity. ⋯ These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder.