ORCID Profile
0000-0001-7867-1160
Current Organisation
University of Texas at Austin Dell Medical School
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Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/15622970410029924
Abstract: As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.
Publisher: Elsevier BV
Date: 1994
DOI: 10.1016/0361-9230(94)90170-8
Abstract: Based on studies of depression and anxiety using animal (rat) models, it is suggested that, contrary to a widely accepted theory, increased activity of locus coeruleus (LC) neurons does not appear to potentiate anxiety instead, the influence of LC activity may be opposite to this. First, studies are described that indicate that behavioral changes resembling what is seen in human clinical depression occur in rats exposed to highly stressful conditions, and the research is then traced, which links this stress-induced depression to disturbance of normal noradrenergic regulation of LC activity. Second, the potential role of corticotrophin releasing factor (CRF) in stress-induced behavioral depression is explored. CRF infused into the LC did not produce behavioral depression in the swim test but did increase anxiety by comparison, CRF infused into the parabrachial nucleus lateral to LC increased both depression and anxiety. Finally, to further explore the relationship between LC activity and anxiety, drugs were infused into LC region to attempt to specifically activate or depress firing of LC neurons. In contrast to expectations, infusion to decrease firing of LC cells increased anxious behavior, while infusion to increase firing decreased anxious behavior. Several other studies are discussed that point to a similar conclusion. It is suggested that, at least in rats, the capacity of stress-inducing or aversive stimuli to activate LC neurons does not potentiate anxiety under environmental conditions that elicit this response, but, rather, the increased activity of the LC/dorsal noradrenergic system under such conditions may exert a counterbalancing, antianxiety influence.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1038/NCOMMS10967
Abstract: DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy in iduals, a locus in the Kit ligand gene ( KITLG cg27512205) showed the strongest association with cortisol stress reactivity ( P =5.8 × 10 −6 ). Replication was obtained in two independent s les using either blood ( N =45, P =0.001) or buccal cells ( N =255, P =0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery s le (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2018
Publisher: Elsevier BV
Date: 12-2014
Publisher: Proceedings of the National Academy of Sciences
Date: 10-10-2016
Abstract: Amygdala reactivity and early life stress (ELS) are both strongly implicated in the mechanisms of depression in animal and human models. Despite these mechanistic foundations, amygdala reactivity and ELS have not been investigated as biobehavioral targets for predicting functional remission in depression. We addressed this issue by integrating human imaging and ELS measures within a controlled trial of antidepressant outcomes. We demonstrate that the interaction between ELS and amygdala engagement predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. In depressed people exposed to high ELS, a greater likelihood of remission was predicted by amygdala hyperreactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, amygdala hyporeactivity to both rewarding and threat-related stimuli predicted remission.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.BIOPSYCH.2010.06.025
Abstract: Depression will be the second largest burden of disease by 2020. Developing new tools for identifying risk and ultimately prevention of depression relies on elucidating the integrative relationships between susceptibility markers from gene-stress interactions and how they impact emotional brain and arousal systems. They have largely been studied in isolation. We examined how genetic (brain-derived neurotrophic factor [BDNF] valine 66 to methionine [Val66Met] and serotonin receptor gene 3A [HTR3A]) and early life stress susceptibility factors interact in predicting electroencephalogram (EEG) asymmetry, emotion-elicited heart rate, and self-reported negativity bias, each correlates of risk for depression. Caucasian volunteers (n = 363) were derived from the Brain Resource International Database, via the Brain Research And Integrative Neuroscience Network. In iduals with both BDNF methionine and HTR3A CC risk genotypes and early life stressors demonstrated a profile of elevated emotion-elicited heart rate and right frontal hyper-activation with right parietotemporal hypoactivation in EEG asymmetry. Elevations in heart rate were a moderator of negativity bias. The findings provide new evidence that these gene-stress susceptibility factors contribute to a brain-arousal profile indicative of risk for depression. They are a step toward identifying biological markers for detecting risk before overt symptoms. It would be valuable for future studies to examine comorbidity and specificity issues for instance, whether these gene-stress factors contribute in different ways to the partially distinct EEG asymmetry profiles found with anxiety.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2009
DOI: 10.1038/MP.2008.143
Abstract: In idual risk markers for depression and anxiety disorders have been identified but the explicit pathways that link genes and environment to these markers remain unknown. Here we examined the explicit interactions between the brain-derived neurotrophic factor (BDNF) Val66Met gene and early life stress (ELS) exposure in brain (amygdala-hippoc al-prefrontal gray matter volume), body (heart rate), temperament and cognition in 374 healthy European volunteers assessed for depression and anxiety symptoms. Brain imaging data were based on a subset of 89 participants. Multiple regression analysis revealed main effects of ELS for body arousal (resting heart rate, P=0.005) and symptoms (depression and anxiety, P<0.001) in the absence of main effects for BDNF. In addition, significant BDNF-ELS interactions indicated that BDNF Met carriers exposed to greater ELS have smaller hippoc al and amygdala volumes (P=0.013), heart rate elevations (P=0.0002) and a decline in working memory (P=0.022). Structural equation path modeling was used to determine if this interaction predicts anxiety and depression by mediating effects on the brain, body and cognitive measures. The combination of Met carrier status and exposure to ELS predicted reduced gray matter in hippoc us (P<0.001), and associated lateral prefrontal cortex (P<0.001) and, in turn, higher depression (P=0.005). Higher depression was associated with poorer working memory (P=0.005), and slowed response speed. The BDNF Met-ELS interaction also predicted elevated neuroticism and higher depression and anxiety by elevations in body arousal (P<0.001). In contrast, the combination of BDNF V/V genotype and ELS predicted increases in gray matter of the amygdala (P=0.003) and associated medial prefrontal cortex (P<0.001), which in turn predicted startle-elicited heart rate variability (P=0.026) and higher anxiety (P=0.026). Higher anxiety was linked to verbal memory, and to impulsivity. These effects were specific to the BDNF gene and were not evident for the related 5HTT-LPR polymorphism. Overall, these findings are consistent with the correlation of depression and anxiety, yet suggest that partially differentiated gene-brain cognition pathways to these syndromes can be identified, even in a nonclinical s le. Such findings may aid establishing an evidence base for more tailored intervention strategies.
Publisher: Society for Neuroscience
Date: 1990
DOI: 10.1523/JNEUROSCI.10-01-00176.1990
Abstract: The present series of experiments tested the hypothesis that the behavioral activating and anxiogenic effects produced by intraventricular administration of corticotropin-releasing factor (CRF) may be mediated by noradrenergic neurons in the brain-stem locus coeruleus (LC). Results showed that infusion of CRF into the LC (100 ng) significantly increased nonambulatory spontaneous motor activity measured in photocell cages ambulatory (i.e., locomotor) activity was not altered. In the modified Porsolt swim test, which examines arousal and agitation in a stressful situation, significant behavioral activation (i.e., decreased floating) was seen following infusion of CRF (10 ng) into the LC a 500 ng dose of CRF was necessary to produce similar effects following infusion into the lateral ventricle. The results of these 2 tests suggest that the behavioral activating effects of CRF in the LC may be related to arousing or stress-related effects, rather than to increased locomotor activity per se. Anxiogenic activity was assessed in animals placed in an open field containing a small, darkened compartment. Infusion or CRF into the LC (1–100 ng) significantly increased the time spent in the compartment and decreased the amount of time spent exploring the outside of the compartment or venturing into the inner squares of the open field, all indices of anxiogenic behavior. Biochemical studies showed that bilateral infusion of CRF into the LC produced significant increases in the concentration of the norepinephrine metabolite 3,4-dihydroxyphenylglycol in such forebrain projection areas of the LC as the amygdala and posterior hypothalamus. These data, taken together, suggest that CRF produces its behavioral activating and anxiogenic effects, at least in part, by increasing the activity of LC noradrenergic neurons.
Publisher: Wiley
Date: 26-01-2005
Publisher: Hindawi Limited
Date: 08-2010
DOI: 10.1002/DA.20726
Abstract: The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptor's localization to brain regions central to emotion processing. Fronto-limbic grey matter (GM) loss was measured using magnetic resonance imaging and assessed using voxel-based morphometry analysis in 397 nonclinical in iduals from the Brain Resource International Database. Negative mood symptoms were also assessed. The HTR3A CC genotype group, compared to the T carriers, demonstrated comparative loss to GM in hippoc al structures, which extended to the frontal cortices for those CC genotype in iduals also exposed to ELS. Elevations in depressed mood were also evident. These findings suggest that the HTR3A CC genotype may be associated with alterations in brain structures central to emotion processing, particularly when exposed to stress, and further highlight the potential role of the serotonin system in the pathophysiology of affective disorders. In contrast, those in iduals with the T allele, in particular the TT genotype, may be more protected from such alterations combined with minimal exposure to ELS events.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1038/NN.3275
Location: United States of America
Location: United States of America
Location: No location found
Location: No location found
Location: United States of America
Location: United States of America
No related grants have been discovered for Charles Nemeroff.