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Chronic Stress

Chadi G Abdallah, Arpan Dutta, Christopher L Averill, Shane McKie, Teddy J Akiki, Lynnette A Averill, J F William Deakin
Background: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment. Methods: Fifty-six unmedicated participants with MDD were randomized to intravenous placebo (normal saline; n = 18), ketamine (0...
January 2018: Chronic Stress
Chung Sub Kim, Daniel Johnston
Growing evidence suggests a possible link between hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels and depression. In a recent study published in Molecular Psychiatry , we first demonstrate that I h (the membrane current mediated by HCN channels) and HCN1 protein expression were increased in dorsal, but not in ventral, CA1 region following chronic, but not acute stress. This upregulation of I h was restricted to the perisomatic region of CA1 neurons and contributed to a reduction of neuronal excitability...
January 2018: Chronic Stress
Jeremy D Coplan, Nishant K Gupta, Sarah K Flynn, Wade J Reiner, David Gaita, Sasha L Fulton, Anna V Rozenboym, Jean E Tang, Thomas B Cooper, J John Mann
Background: Maternal response to allostatic overload during infant rearing may alter neurobiological measures in grown offspring, potentially increasing susceptibility to mood and anxiety disorders. We examined maternal cerebrospinal fluid (CSF) glutamate response during exposure to variable foraging demand (VFD), a bonnet macaque model of allostatic overload, testing whether activation relative to baseline predicted concomitant CSF elevations of the stress neuropeptide, corticotropin-releasing factor...
January 2018: Chronic Stress
Sophie E Holmes, Dustin Scheinost, Nicole DellaGioia, Margaret T Davis, David Matuskey, Robert H Pietrzak, Michelle Hampson, John H Krystal, Irina Esterlis
Background: Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. Methods: We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18)...
January 2018: Chronic Stress
Jeremy D Coplan, Dunyue Lu, Alexander M El Sehamy, Cheuk Tang, Andrea P Jackowski, Chadi G Abdallah, Charles B Nemeroff, Michael J Owens, Sanjay J Mathew, Jack M Gorman
Introduction: Using proton magnetic resonance spectroscopy imaging (1 H-MRSI), the effects of early life stress (ELS) on nonhuman primate striatal neuronal integrity were examined as reflected by N -acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented ELS markers -- cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations, hippocampal volume, body mass and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens (NAcc)...
January 2018: Chronic Stress
Andrew Prescot, Chandni Sheth, Margaret Legarreta, Perry F Renshaw, Erin McGlade, Deborah Yurgelun-Todd
Background: Suicide is a public health concern in the civilian and veteran populations. Stressful life events are precipitating factors for suicide. The neurochemical underpinnings of the association between stress/trauma and suicide risk are unclear, especially in regards to sex differences. We hypothesized that gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter may be a neurochemical candidate that is critical in the association between stress and suicide risk in veterans...
January 2018: Chronic Stress
T G Adams, B Kelmendi, C A Brake, P Gruner, C L Badour, C Pittenger
Individuals with OCD often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a discrete traumatic incident. However, the pathophysiological relationship between stress and OCD remains poorly characterized: it is unclear whether trauma or stress is an independent cause of OCD symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate OCD along with other aspects of psychiatric symptomatology...
January 2018: Chronic Stress
Isaac R Galatzer-Levy, Kelly Ruggles, Zhe Chen
Diverse environmental and biological systems interact to influence individual differences in response to environmental stress. Understanding the nature of these complex relationships can enhance the development of methods to: (1) identify risk, (2) classify individuals as healthy or ill, (3) understand mechanisms of change, and (4) develop effective treatments. The Research Domain Criteria (RDoC) initiative provides a theoretical framework to understand health and illness as the product of multiple inter-related systems but does not provide a framework to characterize or statistically evaluate such complex relationships...
January 2018: Chronic Stress
Terril L Verplaetse, Kelly E Moore, Brian P Pittman, Walter Roberts, Lindsay M Oberleitner, Philip H Smith, Kelly P Cosgrove, Sherry A McKee
Background: Stress contributes to the development and maintenance of substance use disorders (SUD), with some research suggesting that the impact of stress on SUD is greater in women. However, this has yet to be evaluated in a national dataset, across major substances of abuse. Methods: Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n =36,309) we evaluated relationships among past year stressful life events (0 or 1 vs...
January 2018: Chronic Stress
Natalie Matosin, Cristiana Cruceanu, Elisabeth B Binder
Exposure to chronic stress, either repeated severe acute or moderate sustained stress, is one of the strongest risk factors for the development of psychopathologies such as post-traumatic stress disorder and depression. Chronic stress is linked with several lasting biological consequences, particularly to the stress endocrine system but also affecting intermediate phenotypes such as brain structure and function, immune function, and behavior. Although genetic predisposition confers a proportion of the risk, the most relevant molecular mechanisms determining those susceptible and resilient to the effects of stress and trauma may be epigenetic...
February 1, 2017: Chronic Stress
Eric L Garland, Adam W Hanley, Anne K Baker, Matthew O Howard
Mindfulness-based interventions have been heralded as promising means of alleviating chronic stress. While meta-analyses indicate that mindfulness-based interventions significantly reduce global measures of stress, how mindfulness-based interventions modulate the specific mechanisms underpinning chronic stress as operationalized by the National Institute of Mental Health research domain criteria (RDoC) of sustained threat has not yet been detailed in the literature. To address this knowledge gap, this article aims to (1) review evidence that mindfulness-based interventions ameliorate each of the 10 elements of behavioral dysregulation characterizing sustained threat via an array of mindful counter-regulatory strategies; (2) review evidence that mindfulness-based interventions modify biological domains implicated in sustained threat, such as the hypothalamic-pituitary-adrenal axis, as well as brain circuits involved in attentional function, limbic reactivity, habit behavior, and the default mode network; and (3) integrate these findings into a novel conceptual framework of mindful self-regulation in the face of stress-the Mindfulness-to-Meaning Theory...
February 2017: Chronic Stress
Mounira Banasr, Ashley Lepack, Corey Fee, Vanja Duric, Jaime Maldonado-Aviles, Ralph DiLeone, Etienne Sibille, Ronald S Duman, Gerard Sanacora
Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons. Using western blot analyses and quantitative real-time PCR (qPCR) we assessed the effects of five-weeks of chronic unpredictable stress (CUS) exposure on the expression of GABA-synthesizing enzymes (GAD65 and GAD67 ), calcium-binding proteins (calbindin (CB), parvalbumin (PV) and calretinin (CR)), and neuropeptides co-expressed in GABAergic neurons (somatostatin (SST), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK)) in the prefrontal cortex (PFC) and hippocampus (HPC) of rats...
February 2017: Chronic Stress
Teddy J Akiki, Christopher L Averill, Kristen M Wrocklage, Brian Schweinsburg, J Cobb Scott, Brenda Martini, Lynnette A Averill, Steven M Southwick, John H Krystal, Chadi G Abdallah
BACKGROUND: The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. METHODS: In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69)...
February 2017: Chronic Stress
Chadi G Abdallah, Paul Geha
Pain and stress share significant conceptual and physiological overlaps. Both phenomena challenge the body's homeostasis and necessitate decision-making to help animals adapt to their environment. In addition, chronic stress and chronic pain share a common behavioral model of failure to extinguish negative memories. Yet, they also have discrepancies such that the final brain endophenotype of posttraumatic stress disorder, depression, and chronic pain appears to be different among the three conditions, and the role of the hypothalamic-pituitary-adrenal axis remains unclear in the physiology of pain...
February 2017: Chronic Stress
Laura E Kwako, George F Koob
Addiction has been conceptualized as a three-stage cycle- binge/intoxication, withdrawal/negative affect , and preoccupation/anticipation -that worsens over time and involves allostatic changes in hedonic function via changes in the brain reward and stress systems. Using the withdrawal/negative affect stage and negative reinforcement as an important source of motivation for compulsive drug seeking, we outline the neurobiology of the stress component of the withdrawal/negative affect stage and relate it to a derivative of the Research Domain Criteria research construct for the study of psychiatric disease, known as the Addictions Neuroclinical Assessment...
February 2017: Chronic stress
Brendan D Hare, Sriparna Ghosal, Ronald S Duman
Stress-associated disorders, including depression and anxiety, impact nearly 20% of individuals in the United States. The social, health, and economic burden imposed by stress-associated disorders requires in depth research efforts to identify suitable treatment strategies. Traditional medications (e.g., selective serotonin reuptake inhibitors, monoamine oxidase inhibitors) have significant limitations, notably a time lag for therapeutic response that is compounded by low rates of efficacy. Excitement over ketamine, a rapid acting antidepressant effective in treatment resistant patients, is tempered by transient dissociative and psychotomimetic effects, as well as abuse potential...
February 2017: Chronic stress
Lauren M Sippel, Casey E Allington, Robert H Pietrzak, Ilan Harpaz-Rotem, Linda C Mayes, Miranda Olff
Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social-emotional brain. In this review, we present an overview of evidence supporting OT's utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e...
February 2017: Chronic Stress
Shariful A Syed, Charles B Nemeroff
Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective...
February 2017: Chronic Stress
Jeremy D Coplan, Srinath Gopinath, Chadi G Abdallah, Jeffrey Margolis, Wei Chen, Bruce A Scharf, Leonard A Rosenblum, Olcay A Batuman, Eric L P Smith
Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine with anti-inflammatory, immunosuppressive and neuroprotective properties. The hypothalamic-pituitary-adrenal (HPA) axis and immune system exert bidirectional influences on each other, via cortisol and TGF-β1, but the exact nature of the interaction is not well characterized. The current study examined the effects, in bonnet macaques (Macaca radiata), of two consecutive acute confinement stress periods in an unfamiliar room while mildly restrained, first without and then with dexamethasone pretreatment (0...
February 2017: Chronic Stress
Margaret T Davis, Sophie E Holmes, Robert H Pietrzak, Irina Esterlis
Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders...
January 2017: Chronic Stress
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