Publications by authors named "Kyrie Sellnow"

7 Publications

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Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.

Psychoneuroendocrinology 2021 Jul 9;132:105355. Epub 2021 Jul 9.

University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, 1601 Trinity St, Bldg B, Austin, TX 78712, United States.

Introduction: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall.

Methods: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect.

Results: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005).

Conclusions: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105355DOI Listing
July 2021

Aerobic exercise and consolidation of fear extinction learning among women with posttraumatic stress disorder.

Behav Res Ther 2021 07 27;142:103867. Epub 2021 Apr 27.

University of Wisconsin, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI, 53719-1176, USA. Electronic address:

This study tested whether aerobic exercise delivered during the consolidation window following fear extinction learning reduces the return of fear among women with posttraumatic stress disorder (PTSD). Participants (n=35) completed an initial clinical assessment followed by a 3-day fear acquisition, extinction, and recall protocol. On day 1, participants completed a fear acquisition training task in which one geometric shape (conditioning stimulus; CS+) was paired (with 50% probability) with a mild electric shock (unconditioned stimulus; US), while a different shape (CS-) was never paired with the US. On day 2 (24 h later), participants completed a fear extinction training task in which the CS+ no longer predicted administration of the US. Shortly following extinction, participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity exercise control (CON) condition. On day 3 (24 h later), participants completed fear recall tests assessing the return of fear (spontaneous recovery, renewal, and reinstatement). Fear responding was assessed via threat expectancy ratings and skin conductance responses (SCR). In the threat expectancy ratings, there were no significant differences between groups in spontaneous recovery; however, EX significantly (p=.02) reduced threat expectancy ratings following reinstatement relative to CON. In SCR measures, there were no significant differences between groups in spontaneous recovery, renewal, or reinstatement. These results support a role for moderate-intensity aerobic exercise during the consolidation window in reducing threat expectations following reinstatement in women with PTSD. Research should continue to examine exercise as a potential method for improving the efficacy of exposure-based therapies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04113798.
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http://dx.doi.org/10.1016/j.brat.2021.103867DOI Listing
July 2021

L-DOPA and consolidation of fear extinction learning among women with posttraumatic stress disorder.

Transl Psychiatry 2020 08 15;10(1):287. Epub 2020 Aug 15.

University of Arkansas for Medical Sciences, Brain Imaging Research Center, Little Rock, AR, USA.

This study tested whether L-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg L-DOPA/carbidopa (n = 28), or 200/50 mg L-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of L-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that L-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.
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http://dx.doi.org/10.1038/s41398-020-00975-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429959PMC
August 2020

Sacrificing reward to avoid threat: Characterizing PTSD in the context of a trauma-related approach-avoidance conflict task.

J Abnorm Psychol 2020 Jul 21;129(5):457-468. Epub 2020 May 21.

Department of Psychiatry, University of Wisconsin-Madison.

Posttraumatic stress disorder (PTSD) is characterized by heightened avoidance, cognitive inflexibility, and impaired reward processing. Maladaptive behavior in PTSD may reflect an imbalance between approach and avoidance, but no research has investigated approach-avoidance conflict (AAC) in PTSD. The current study investigated approach-avoidance behavior in PTSD using a trauma-related AAC (trAAC) task in two independent samples. In Study 1, 43 women with a current diagnosis of PTSD and 18 healthy comparison subjects were recruited from the community. In Study 2, 53 women with trauma exposure and a range of PTSD symptoms were recruited from a correctional institution. Trials were separated into two phases: conflict (the option most likely to win points was most likely to show a trauma-related image) and congruent (the option most likely to win points was least likely to show a trauma-related image). In Study 1, reward obtainment varied with the task manipulation (i.e., fewer points earned during conflict compared to congruent Phase) in PTSD but not healthy subjects. These results indicate that when avoidance is advantageous (congruent phase), individuals with PTSD show increased task performance, whereas when avoidance is maladaptive (conflict phase), individuals with PTSD show increased sacrifice of reward. In Study 2, higher PTSD symptoms predicted decreased reward earning during the conflict phase, again indicating a sacrifice of reward when avoidance is maladaptive. Across both studies, PTSD associated with increased AAC and sacrifice of reward in the presence of trauma-related stimuli. These studies shed light on AAC in PTSD and could inform more targeted therapy approaches. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393639PMC
July 2020

Biotypes of functional brain engagement during emotion processing differentiate heterogeneity in internalizing symptoms and interpersonal violence histories among adolescent girls.

J Psychiatr Res 2020 02 6;121:197-206. Epub 2019 Dec 6.

University of Wisconsin Madison, Department of Psychiatry, USA. Electronic address:

Youth exposed to early life interpersonal violence (IPV) demonstrate heterogeneous clinical symptoms. Studies based on univariate methods suggest that neurocircuitry related to emotion processing explains heterogeneity in internalizing symptoms. Here, we use a multivariate, data-driven method of identifying distinct functional brain activation profiles (i.e., "biotypes") and test whether these biotypes differentiate internalizing symptoms among IPV-exposed youth. 114 adolescent girls (n = 38 with no IPV exposure or psychopathology; n = 76 with IPV exposure and heterogeneous internalizing symptoms), aged 11-17, completed an emotion processing task during fMRI. To identify distinct biotypes of brain engagement profiles, data-driven clustering analysis was applied to patterns of voxel activation, constrained within a mask of distributed regions implicated in emotion processing. Resulting biotypes (BT1-3) were compared on measures of IPV exposure and internalizing symptoms, as well as symptom reduction during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) among a subset of participants (n = 21). Cluster analyses identified three biotypes, differentiated by engagement of medial prefrontal, anterior insula, hippocampus, parietal, and ventral visual cortex during emotion processing. BT1 exhibited low levels of IPV exposure and internalizing symptoms. BT2 exhibited elevated levels of IPV, except sexual assault, and demonstrated moderate severity across internalizing symptom domains. BT3 exhibited elevated severity across all IPV and internalizing symptom domains. Greater symptom reduction during TF-CBT was associated with increased pre-to post-treatment changes in similarity with BT1. These results demonstrate distinct profiles of emotion processing neurocircuitry that differentiate heterogeneity in internalizing symptoms in IPV-exposed adolescent girls.
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http://dx.doi.org/10.1016/j.jpsychires.2019.12.002DOI Listing
February 2020

Social Trust and Reciprocity Among Adolescent Girls Exposed to Interpersonal Violence.

J Interpers Violence 2019 Oct 14:886260519881522. Epub 2019 Oct 14.

University of Wisconsin-Madison, USA.

Trauma research has traditionally focused on altered emotion regulation and its role in psychopathology, whereas mechanisms of social behavior remain comparatively unexplored, particularly among adolescents. It has been previously reported that adolescents with histories of interpersonal violence (IV) demonstrate disrupted social learning, and the degree to which they are impaired during social interactions requiring trustful behaviors may be associated with their levels of anxiety. In the present study, 52 adolescent females ( = 26 control; = 26 IV-exposed) between ages of 11 and 17 completed a multi-round adaptation of the Trust Game in which they interacted with a confederate peer run by a computer program, alternating between the roles of investor and investee. The task was designed to operationalize the social behaviors of trust and trust reciprocity, where the magnitude of the participants' monetary investment in the confederate during the investor role represented trust while the proportion of investment returned to the confederate in the investee role represented trust reciprocity. IV-exposed and control participants did not differ in trust (i.e., as investors); however, IV-exposed participants without anxiety diagnoses demonstrated lower trust than those with anxiety diagnoses. For trust reciprocity (i.e., as investees), there were again no differences between IV-exposed participants and controls; however, IV-exposed participants with anxiety diagnoses had increased trust reciprocity compared with both other groups. Similarly, caregiver-reported anxiety symptoms were associated with trust reciprocity behaviors among the IV-exposed adolescents. Findings suggest that IV exposure and associated anxiety impacts adolescents' trust behaviors, demonstrating potential mechanisms for maladaptive social behavior among trauma-exposed youth.
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http://dx.doi.org/10.1177/0886260519881522DOI Listing
October 2019

Differential Roles of the Salience Network During Prediction Error Encoding and Facial Emotion Processing Among Female Adolescent Assault Victims.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 04 11;4(4):371-380. Epub 2018 Sep 11.

Brain Imaging Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Background: Early-life assaultive violence exposure is a potent risk factor for posttraumatic stress disorder (PTSD) and other mood and anxiety disorders. Neurocircuitry models posit that increased risk is mediated by heightened emotion processing in a salience network including the dorsal anterior cingulate cortex, anterior insula, and amygdala. However, the processes of reinforcement learning (RL) also engage the salience network and are implicated in responses to early-life trauma and PTSD. To define their relative roles in response to early-life trauma and PTSD symptoms, the current study compared engagement of the salience network during emotion processing and RL as a function of early-life assault exposure.

Methods: Adolescent girls (n = 30 girls who had previously been physically or sexually assaulted; n = 30 healthy girls for comparison) 11 to 17 years of age completed two types of tasks during functional magnetic resonance imaging: a facial emotion processing task and an RL task using either social or nonsocial stimuli. Independent component analysis was used to identify a salience network and characterize its engagement in response to emotion processing and prediction error encoding during the RL tasks.

Results: Assault was related to greater reactivity of the salience network during emotion processing. By contrast, we found lesser encoding of negative prediction errors in the salience network, particularly during the social RL task, in girls who had been assaulted. The dysfunction of salience network activity during emotion processing and prediction error encoding was not associated with PTSD symptoms.

Conclusions: These results suggest that hyper- versus hypoactivity of the salience network among trauma-exposed youths depends on the cognitive-affective domain.
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http://dx.doi.org/10.1016/j.bpsc.2018.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638574PMC
April 2019
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