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Biological Psychiatry

Mark A Geyer, Svetlana Semenova, Xia Li, Andre Der-Avakian, Samuel A Barnes, Igor Grant
No abstract text is available yet for this article.
February 28, 2018: Biological Psychiatry
Thomas H McCoy, Sheng Yu, Kamber L Hart, Victor M Castro, Hannah E Brown, James N Rosenquist, Alysa E Doyle, Pieter J Vuijk, Tianxi Cai, Roy H Perlis
BACKGROUND: Relying on diagnostic categories of neuropsychiatric illness obscures the complexity of these disorders. Capturing multiple dimensional measures of neuropathology could facilitate the clinical and neurobiological investigation of cognitive and behavioral phenotypes. METHODS: We developed a natural language processing-based approach to extract five symptom dimensions, based on the National Institute of Mental Health Research Domain Criteria definitions, from narrative clinical notes...
February 23, 2018: Biological Psychiatry
Thomas H McCoy, Victor M Castro, Kamber L Hart, Amelia M Pellegrini, Sheng Yu, Tianxi Cai, Roy H Perlis
BACKGROUND: Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown. METHODS: We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank...
February 20, 2018: Biological Psychiatry
Martin Picard, Aric A Prather, Eli Puterman, Alexanne Cuillerier, Michael Coccia, Kirstin Aschbacher, Yan Burelle, Elissa S Epel
BACKGROUND: Chronic life stress, such as the stress of caregiving, can promote pathophysiology, but the underlying cellular mechanisms are not well understood. Chronic stress may induce recalibrations in mitochondria leading to changes either in mitochondrial content per cell, or in mitochondrial functional capacity (i.e., quality). METHODS: Here we present a functional index of mitochondrial health (MHI) for human leukocytes that can distinguish between these two possibilities...
February 3, 2018: Biological Psychiatry
Timothy M Locke, Marta E Soden, Samara M Miller, Avery Hunker, Cerise Knakal, Julia A Licholai, Karn S Dhillon, C Dirk Keene, Larry S Zweifel, Erik S Carlson
BACKGROUND: Studies in humans and nonhuman primates have identified a region of the dentate nucleus of the cerebellum, or the lateral cerebellar nucleus (LCN) in rodents, activated during performance of cognitive tasks involving complex spatial and sequential planning. Whether such a subdivision exists in rodents is not known. Dopamine and its receptors, which are implicated in cognitive function, are present in the cerebellar nuclei, but their function is unknown. METHODS: Using viral and genetic strategies in mice, we examined cellular phenotypes of dopamine D1 receptor-positive (D1R+) cells in the LCN with whole-cell patch clamp recordings, messenger RNA profiling, and immunohistochemistry to examine D1R expression in mouse LCN and human dentate nucleus of the cerebellum...
February 2, 2018: Biological Psychiatry
Julie E Finnell, Brandon L Muniz, Akhila R Padi, Calliandra M Lombard, Casey M Moffitt, Christopher S Wood, L Britt Wilson, Lawrence P Reagan, Marlene A Wilson, Susan K Wood
BACKGROUND: Women are at greater risk than men of developing depression and comorbid disorders such as cardiovascular disease. This enhanced risk begins at puberty and ends following menopause, suggesting a role for ovarian hormones in this sensitivity. Here we used a model of psychosocial witness stress in female rats to determine the stress-induced neurobiological adaptations that underlie stress susceptibility in an ovarian hormone-dependent manner. METHODS: Intact or ovariectomized (OVX) female rats were exposed to five daily 15-minute witness-stress exposures...
January 31, 2018: Biological Psychiatry
Mònica Guxens, Małgorzata J Lubczyńska, Ryan L Muetzel, Albert Dalmau-Bueno, Vincent W V Jaddoe, Gerard Hoek, Aad van der Lugt, Frank C Verhulst, Tonya White, Bert Brunekreef, Henning Tiemeier, Hanan El Marroun
BACKGROUND: Air pollution exposure during fetal life has been related to impaired child neurodevelopment, but it is unclear if brain structural alterations underlie this association. The authors assessed whether air pollution exposure during fetal life alters brain morphology and whether these alterations mediate the association between air pollution exposure during fetal life and cognitive function in school-age children. METHODS: We used data from a population-based birth cohort set up in Rotterdam, The Netherlands (2002-2006)...
January 31, 2018: Biological Psychiatry
Thaddeus S Block, Harvey Kushner, Ned Kalin, Craig Nelson, Joseph Belanoff, Alan Schatzberg
BACKGROUND: Patients with psychotic depression exhibit elevated cortisol levels. Competitively antagonizing cortisol at the glucocorticoid receptor with mifepristone demonstrated therapeutic benefit in early studies of patients with psychotic depression. We present a combined analysis of all controlled phase 2 and 3 studies to report antipsychotic differences between treatment with mifepristone or placebo and to evaluate the relative contributions to response of attaining an a priori-defined, high mifepristone plasma level and markers of glucocorticoid receptor antagonism (increases in adrenocorticotropin hormone and cortisol) with treatment...
January 31, 2018: Biological Psychiatry
Diego E Pafundo, Takeaki Miyamae, David A Lewis, Guillermo Gonzalez-Burgos
BACKGROUND: Testing hypotheses regarding the role of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia requires understanding the mechanisms of NMDAR regulation of prefrontal cortex (PFC) circuit function. NMDAR antagonists are thought to produce pyramidal cell (PC) disinhibition. However, inhibitory parvalbumin-positive basket cells (PVBCs) have modest NMDAR-mediated excitatory drive and thus are unlikely to participate in NMDAR antagonist-mediated disinhibition. Interestingly, recent studies demonstrated that presynaptic NMDARs enhance transmitter release at central synapses...
January 31, 2018: Biological Psychiatry
Jeremy Hogeveen, Marie K Krug, Matthew V Elliott, Marjorie Solomon
BACKGROUND: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. METHODS: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53)...
January 31, 2018: Biological Psychiatry
Deepak Cyril D'Souza, Richard E Carson, Naomi Driesen, Jason Johannesen, Mohini Ranganathan, John H Krystal
BACKGROUND: Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. METHODS: In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects...
January 31, 2018: Biological Psychiatry
Anthony G Phillips, Mark A Geyer, Trevor W Robbins
Athina Markou and others argue forcefully for the adoption of a "translational-back translational strategy" for central nervous system drug discovery involving novel application of drugs with established safety profiles in proof-of-principle studies in humans, which in turn encourage parallel studies using experimental animals to provide vital data on the neural systems and neuropharmacological mechanisms related to the actions of the candidate drugs. Encouraged by the increasing adoption of drug-development strategies involving reciprocal information exchange between preclinical animal studies and related clinical research programs, this review presents additional compelling examples related to the following: 1) the treatment of cognitive deficits that define attention-deficit/hyperactivity disorder; 2) the development of fast-acting antidepressants based on promising clinical effects with low doses of the anesthetic ketamine; and 3) new and effective medications for the treatment of substance misuse...
January 31, 2018: Biological Psychiatry
Rupali Srivastava, Travis Faust, Adriana Ramos, Koko Ishizuka, Akira Sawa
Mitochondria play a crucial role in neuronal function, especially in energy production, the generation of reactive oxygen species, and calcium signaling. Multiple lines of evidence have suggested the possible involvement of mitochondrial deficits in major psychiatric disorders, such as schizophrenia and bipolar disorder. This review will outline the current understanding of the physiological role of mitochondria and their dysfunction under pathological conditions, particularly in psychiatric disorders. The current knowledge about mitochondrial deficits in these disorders is somewhat limited because of the lack of effective methods to dissect dynamic changes in functional deficits that are directly associated with psychiatric conditions...
January 17, 2018: Biological Psychiatry
Diana L Castillo-Carranza, Marcos J Guerrero-Muñoz, Urmi Sengupta, Julia E Gerson, Rakez Kayed
BACKGROUND: The coexistence of α-synuclein and tau aggregates in several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, raises the possibility that a seeding mechanism is involved in disease progression. METHODS: To further investigate the role of α-synuclein in the tau aggregation pathway, we performed a set of experiments using both recombinant and brain-derived tau and α-synuclein oligomers to seed monomeric tau aggregation in vitro and in vivo...
January 17, 2018: Biological Psychiatry
Jessica Tooley, Lauren Marconi, Jason Bondoc Alipio, Bridget Matikainen-Ankney, Polymnia Georgiou, Alexxai V Kravitz, Meaghan C Creed
BACKGROUND: 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...
January 12, 2018: Biological Psychiatry
Zhongshan Cheng, Hang Zhou, Richard Sherva, Lindsay A Farrer, Henry R Kranzler, Joel Gelernter
BACKGROUND: Opioid dependence (OD) is at epidemic levels in the United States. Genetic studies can provide insight into its biology. METHODS: We completed an OD genome-wide association study in 3058 opioid-exposed European Americans, 1290 of whom met criteria for a DSM-IV diagnosis of OD. Analysis used DSM-IV criterion count. RESULTS: By meta-analysis of four cohorts, Yale-Penn 1 (n = 1388), Yale-Penn 2 (n = 996), Yale-Penn 3 (n = 98), and SAGE (Study of Addiction: Genetics and Environment) (n = 576), we identified a variant on chromosome 15, rs12442183, near RGMA, associated with OD (p = 1...
January 11, 2018: Biological Psychiatry
Marion Rouault, Tricia Seow, Claire M Gillan, Stephen M Fleming
BACKGROUND: Distortions in metacognition-the ability to reflect on and control other cognitive processes-are thought to be characteristic of poor mental health. However, it remains unknown whether such shifts in self-evaluation are due to specific alterations in metacognition and/or a downstream consequence of changes in decision-making processes. METHODS: Using perceptual decision making as a model system, we employed a computational psychiatry approach to relate parameters governing both decision formation and metacognitive evaluation to self-reported transdiagnostic symptom dimensions in a large general population sample (N = 995)...
January 11, 2018: Biological Psychiatry
Andrew A Nierenberg, Sharmin A Ghaznavi, Isadora Sande Mathias, Kristen K Ellard, Jessica A Janos, Louisa G Sylvia
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions...
January 10, 2018: Biological Psychiatry
Frauke Nees, Stephanie H Witt, Herta Flor
In this review article, genetic variation associated with brain responses related to acute and chronic stress reactivity and fear learning in humans is presented as an important mechanism underlying posttraumatic stress disorder. We report that genes related to the regulation of the hypothalamic-pituitary-adrenal axis, as well as genes that modulate serotonergic, dopaminergic, and neuropeptidergic functions or plasticity, play a role in this context. The strong overlap of the genetic targets involved in stress and fear learning suggests that a dimensional and mechanistic model of the development of posttraumatic stress disorder based on these constructs is promising...
January 10, 2018: Biological Psychiatry
Angélique Quartier, Laure Chatrousse, Claire Redin, Céline Keime, Nicolas Haumesser, Anne Maglott-Roth, Laurent Brino, Stéphanie Le Gras, Alexandra Benchoua, Jean-Louis Mandel, Amélie Piton
BACKGROUND: Prenatal exposure to androgens during brain development in male individuals may participate to increase their susceptibility to develop neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability. However, little is known about the action of androgens in human neural cells. METHODS: We used human neural stem cells differentiated from embryonic stem cells to investigate targets of androgens. RESULTS: RNA sequencing revealed that treatment with dihydrotestosterone (DHT) leads to subtle but significant changes in the expression of about 200 genes, encoding proteins of extracellular matrix or involved in signal transduction of growth factors (e...
January 9, 2018: Biological Psychiatry
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