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Filter Results:

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Article

CYTOKINE TARGETS IN THE BRAIN: IMPACT ON NEUROTRANSMITTERS AND NEUROCIRCUITS

by Andrew H Miller; Ebrahim Haroon; Charles L. Raison; Jennifer Felger

2013

Subjects
  • Psychology, Clinical
  • Psychology, Cognitive
  • Psychology, Physiological
  • View Abstract

Abstract:Close

Increasing attention has been paid to the role of inflammation in a host of illnesses including neuropsychiatric disorders such as depression and anxiety. Activation of the inflammatory response leads to release of inflammatory cytokines and mobilization of immune cells both of which have been shown to access the brain and alter behavior. The mechanisms of the effects of inflammation on the brain have become an area of intensive study. Data indicate that cytokines and their signaling pathways including p38 mitogen-activated protein kinase have significant effects on the metabolism of multiple neurotransmitters such as serotonin, dopamine, and glutamate through impact on their synthesis, release, and reuptake. Cytokines also activate the kynurenine pathway, which not only depletes tryptophan, the primary amino acid precursor of serotonin, but also generates neuroactive metabolites that can significantly influence the regulation of dopamine and glutamate. Through their effects on neurotransmitter systems, cytokines impact neurocircuits in the brain including the basal ganglia and anterior cingulate cortex, leading to significant changes in motor activity and motivation as well as anxiety, arousal, and alarm. In the context of environmental challenge from the microbial world, these effects of inflammatory cytokines on the brain represent an orchestrated suite of behavioral and immune responses that subserve evolutionary priorities to shunt metabolic resources away from environmental exploration to fighting infection and wound healing, while also maintaining vigilance against attack, injury, and further pathogen exposure. Chronic activation of this innate behavioral and immune response may lead to depression and anxiety disorders in vulnerable individuals. © 2013 Wiley Periodicals, Inc.

Article

Prospective Associations between Emotion Dysregulation and Fear-Potentiated Startle: The Moderating Effect of Respiratory Sinus Arrhythmia

by Antonia V. Seligowski; Daniel J. Lee; Lynsey R. Miron; Holly K. Orcutt; Tanja Jovanovic; Seth Norrholm

2016

Subjects
  • Psychology, Behavioral
  • Psychology, Physiological
  • File Download
  • View Abstract

Abstract:Close

Background: Emotion dysregulation has been implicated in the negative outcomes following trauma exposure. A proposed biomarker of emotion dysregulation, respiratory sinus arrhythmia (RSA), has demonstrated associations with trauma-related phenomena, such as the fear-potentiated startle (FPS) response. The current study aimed to examine the prospective association between emotion dysregulation and RSA and FPS several years following trauma exposure. Methods: Participants were 131 women exposed to a campus mass shooting on February 14, 2008. Pre-shooting emotion dysregulation was assessed in 2006-2008. Startle response, measured by orbicularis oculi electromyography (EMG), and RSA were gathered during an FPS paradigm conducted from 2012 to 2015. Results: No significant associations among emotion dysregulation, RSA, and FPS emerged among the full sample. However, emotion dysregulation predicted FPS during both acquisition (r = 0.40, p < 0.05) and extinction (r = 0.57, p < 0.01) among individuals with high resting RSA. Conclusions: Findings suggest that pre-shooting emotion dysregulation is a potent predictor of FPS several years following potential trauma exposure, and this association varies by RSA level. Results emphasize the importance of examining autonomic regulation in the association between emotion dysregulation and recovery from trauma exposure.

Article

Fear conditioned responses and PTSD symptoms in children: Sex differences in fear-related symptoms

by Kaitlyn Gamwell; Maria Nylocks; Dorthie Cross; Bekh Bradley-Davino; Seth Norrholm; Tanja Jovanovic

2015

Subjects
  • Psychology, Clinical
  • Psychology, Physiological
  • Health Sciences, Mental Health
  • File Download
  • View Abstract

Abstract:Close

Fear conditioning studies in adults have found that posttraumatic stress disorder (PTSD) is associated with heightened fear responses and impaired discrimination. The objective of the current study was to examine the association between PTSD symptoms and fear conditioned responses in children from a highly traumatized urban population. Children between 8 and 13 years old participated in a fear conditioning study in addition to providing information about their trauma history and PTSD symptoms. Results showed that females showed less discrimination between danger and safety signals during conditioning compared to age-matched males. In boys, intrusive symptoms were predictive of fear responses, even after controlling for trauma exposure. However, in girls, conditioned fear to the danger cue was predictive of self-blame and fear of repeated trauma. This study suggests there are early sex differences in the patterns of fear conditioning and that these sex differences may translate to differential risk for trauma-related psychopathology.

Article

Tools for translational neuroscience: PTSD is associated with heightened fear responses using acoustic startle but not skin conductance measures

by Ebony M. Glover; Justine E. Phifer; Daniel F. Crain; Seth Norrholm; Michael Davis; Bekh Bradley-Davino; Kerry Ressler; Tanja Jovanovic

2011

Subjects
  • Biology, Neuroscience
  • Psychology, Clinical
  • Psychology, Physiological
  • File Download
  • View Abstract

Abstract:Close

Background: Posttraumatic stress disorder (PTSD) patients show heightened fear responses to trauma reminders and an inability to inhibit fear in the presence of safety reminders. Brain imaging studies suggest that this is in part due to amygdala over-reactivity as well as deficient top-down cortical inhibition of the amygdala. Consistent with these findings, previous studies, using fear-potentiated startle (FPS), have shown exaggerated startle and deficits in fear inhibition in PTSD participants. However, many PTSD studies using the skin conductance response (SCR) report no group differences in fear acquisition. Method: The study included 41 participants with PTSD and 70 without PTSD. The fear conditioning session included a reinforced conditioned stimulus (CS+, danger cue) paired with an aversive airblast, and a nonreinforced conditioned stimulus (CS-, safety cue). Acoustic startle responses and SCR were acquired during the presentation of each CS. Results: The results showed that fear conditioned responses were captured in both the FPS and SCR measures. Furthermore, PTSD participants had higher FPS to the danger cue and safety cue compared to trauma controls. However, SCR did not differ between groups. Finally, we found that FPS to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD symptom variance. Conclusions: Replicating earlier studies, we showed increased FPS in PTSD participants. However, although SCR was a good measure of differential conditioning, it did not differentiate between PTSD groups. These data suggest that FPS may be a useful tool for translational research.

Article

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

by Seth Norrholm; Tanja Jovanovic; Maryrose Gerardi; Kathryn G. Breazeale; Matthew Price; Michael Davis; Erica Duncan; Kerry Ressler; Bekh Bradley-Davino; Albert Rizzo; Peter W. Tuerk; Barbara Rothbaum

2016

Subjects
  • Psychology, Physiological
  • Psychology, Behavioral
  • Psychology, Clinical
  • File Download
  • View Abstract

Abstract:Close

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS).
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