ABSTRACT
Background: The prevalence of posttraumatic stress disorder (PTSD) among people living with HIV (PLWH) is higher than in the general population and can impact health behaviors. The influence of HIV on PTSD psychophysiology requires further investigation due to implications for the treatment of PTSD in PLWH. Objective: Utilizing fear-potentiated startle (FPS), we aimed to interrogate the influence of PTSD and HIV on fear responses. Materials and Methods: Women (18-65 years of age) recruited from the Women's Interagency HIV Study in Atlanta, GA (n = 70, 26 without HIV and 44 with HIV), provided informed consent and completed a semistructured interview to assess trauma exposure and PTSD symptom severity. Participants also underwent an FPS paradigm to assess fear acquisition and extinction: Psychophysiological indices that measure how individuals learn new fear and then subsequently attempt to suppress this fear. Results: Women with PTSD, who did not have HIV, exhibited a greater startle response compared to women without PTSD or HIV during late acquisition to both the danger cue, reinforced conditioned stimulus (CS+, p = 0.013)), and the safety cue, non-reinforced conditioned stimulus (CS-, p = 0.046)), whereas women living with HIV (WLH) and PTSD demonstrated blunted fear responses compared to women with PTSD only. During extinction, WLH comorbid with PTSD exhibited an increased fear response during the extinction period in comparison to all other groups (p = 0.023). Women without PTSD demonstrated a reduction in the fear response during extinction regardless of HIV status. Conclusion: Our findings indicate that HIV further modifies fear psychophysiology in WLH with comorbid PTSD, highlighting the importance of considering HIV status in conjunction with PTSD treatment.
ABSTRACT
Importance: Current interventions for posttraumatic stress disorder (PTSD) are efficacious, yet effectiveness may be limited by adverse effects and high withdrawal rates. Acupuncture is an emerging intervention with positive preliminary data for PTSD. Objective: To compare verum acupuncture with sham acupuncture (minimal needling) on clinical and physiological outcomes. Design, Setting, and Participants: This was a 2-arm, parallel-group, prospective blinded randomized clinical trial hypothesizing superiority of verum to sham acupuncture. The study was conducted at a single outpatient-based site, the Tibor Rubin VA Medical Center in Long Beach, California, with recruitment from April 2018 to May 2022, followed by a 15-week treatment period. Following exclusion for characteristics that are known PTSD treatment confounds, might affect biological assessment, indicate past nonadherence or treatment resistance, or indicate risk of harm, 93 treatment-seeking combat veterans with PTSD aged 18 to 55 years were allocated to group by adaptive randomization and 71 participants completed the intervention protocols. Interventions: Verum and sham were provided as 1-hour sessions, twice weekly, and participants were given 15 weeks to complete up to 24 sessions. Main Outcomes and Measures: The primary outcome was pretreatment to posttreatment change in PTSD symptom severity on the Clinician-Administered PTSD Scale-5 (CAPS-5). The secondary outcome was pretreatment to posttreatment change in fear-conditioned extinction, assessed by fear-potentiated startle response. Outcomes were assessed at pretreatment, midtreatment, and posttreatment. General linear models comparing within- and between-group were analyzed in both intention-to-treat (ITT) and treatment-completed models. Results: A total of 85 male and 8 female veterans (mean [SD] age, 39.2 [8.5] years) were randomized. There was a large treatment effect of verum (Cohen d, 1.17), a moderate effect of sham (d, 0.67), and a moderate between-group effect favoring verum (mean [SD] Δ, 7.1 [11.8]; t90 = 2.87, d, 0.63; P = .005) in the intention-to-treat analysis. The effect pattern was similar in the treatment-completed analysis: verum d, 1.53; sham d, 0.86; between-group mean (SD) Δ, 7.4 (11.7); t69 = 2.64; d, 0.63; P = .01). There was a significant pretreatment to posttreatment reduction of fear-potentiated startle during extinction (ie, better fear extinction) in the verum but not the sham group and a significant correlation (r = 0.31) between symptom reduction and fear extinction. Withdrawal rates were low. Conclusions and Relevance: The acupuncture intervention used in this study was clinically efficacious and favorably affected the psychobiology of PTSD in combat veterans. These data build on extant literature and suggest that clinical implementation of acupuncture for PTSD, along with further research about comparative efficacy, durability, and mechanisms of effects, is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02869646.
Subject(s)
Combat Disorders , Stress Disorders, Post-Traumatic , Veterans , Humans , Adult , Male , Stress Disorders, Post-Traumatic/therapy , Female , Middle Aged , Combat Disorders/therapy , Combat Disorders/psychology , Veterans/psychology , Young Adult , Treatment Outcome , Acupuncture Therapy/methods , Reflex, Startle/physiology , Prospective Studies , Acupuncture, Ear/methodsABSTRACT
OBJECTIVES: The primary objective was to estimate the prevalence of hyperacusis diagnosis in treatment-seeking Veterans, paying attention to when it is diagnosed in conjuncture with common comorbid conditions. DESIGN: This retrospective observational study used Veteran electronic health records from January 2015 to July 2021. Hyperacusis and comorbid conditions were identified using International Classification of Disease diagnostic codes. RESULTS: The prevalence of hyperacusis diagnosis was 0.06%. Veterans diagnosed with tinnitus, posttraumatic stress disorder, headache, or traumatic brain injury were between two and seven times more likely to have an International Classification of Disease code for hyperacusis. CONCLUSIONS: The estimated prevalence of hyperacusis diagnosis using electronic health records is grossly below what is reported in the literature. This is likely due to lack of standardized methods to diagnosis hyperacusis and when present with comorbid conditions, uncertainty when it should be coded as a secondary diagnosis. Future clinical and research efforts prioritizing hyperacusis are desperately needed.
Subject(s)
Tinnitus , Veterans , Humans , Hyperacusis/diagnosis , Hyperacusis/epidemiology , Hyperacusis/complications , Prevalence , Tinnitus/epidemiology , Tinnitus/complications , Delivery of Health CareABSTRACT
The focus of this chapter is an overview of integrating virtual reality (VR) technology within the context of exposure therapy for anxiety disorders, a gold standard treatment, with a focus on how VR can help facilitate extinction learning processes integral to these interventions. The chapter will include an overview of advantages of incorporating VR within exposure therapy, and benefits specifically within an inhibitory learning approach for extinction training. A review of the empirical literature on the effectiveness of VR exposure therapy for specific phobia and PTSD will be provided, as well as practical overview of how to effectively incorporate VR within exposure therapy.
Subject(s)
Implosive Therapy , Phobic Disorders , Virtual Reality Exposure Therapy , Virtual Reality , Humans , Phobic Disorders/therapy , Anxiety DisordersABSTRACT
BACKGROUND: Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (µ) opioid receptors. Whereas naltrexone blocks all µ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. METHODS: Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. RESULTS: Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). CONCLUSIONS: This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.
ABSTRACT
Few studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS-), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS-, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders.
ABSTRACT
The COVID-19 pandemic is a rare stressor that has precipitated an accompanying mental health crisis. Prospective studies traversing the pandemic's onset can elucidate how pre-existing disease vulnerabilities augured risk for later stress-related morbidity. We examined how pre-pandemic sleep reactivity predicted maladaptive stress reactions and depressive symptoms in response to, and during, the pandemic. This study is a secondary analysis of a randomised controlled trial from 2016 to 2017 comparing digital cognitive behavioural therapy for insomnia (dCBT-I) against sleep education (N = 208). Thus, we also assessed whether dCBT-I moderated the association between pre-pandemic sleep reactivity and pandemic-related distress. Pre-pandemic sleep reactivity was measured at baseline using the Ford Insomnia Response to Stress Test. In April 2020, participants were recontacted to report pandemic-related distress (stress reactions and depression). Controlling for the treatment condition and the degree of COVID-19 impact, higher pre-pandemic sleep reactivity predicted more stress reactions (ß = 0.13, ± 0.07 SE, p = 0.045) and depression (ß = 0.22, ± 0.07 SE, p = 0.001) during the pandemic. Further, the odds of reporting clinically significant stress reactions and depression during the pandemic were over twice as high in those with high pre-pandemic sleep reactivity. Notably, receiving dCBT-I in 2016-2017 mitigated the relationship between pre-pandemic sleep reactivity and later stress reactions (but not depression). Pre-pandemic sleep reactivity predicted psychological distress 3-4 years later during the COVID-19 pandemic, and dCBT-I attenuated its association with stress reactions, specifically. Sleep reactivity may inform prevention and treatment efforts by identifying individuals at risk of impairment following stressful events.
Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/therapy , Pandemics , Prospective Studies , Sleep/physiologyABSTRACT
Background: The transition to adulthood is a period of increased risk for emergent psychopathology; emerging adults with a childhood maltreatment history are at risk for poor outcomes. Method: Using a multi-measure, transdisciplinary, cross-sectional design, this study tested whether participant-reported positive parenting, a potential resilience-promoting factor, moderated the association between clinician-rated PTSD symptom severity and a transdiagnostic maladjustment biomarker, fear-potentiated startle (FPS), in a sample of 66 emerging adults (Myears = 18.83, SD = 0.89) with a maltreatment history. We hypothesized that characteristics of effective parenting would moderate the relation between PTSD symptoms and FPS. Results: Results indicated that elevated PTSD, as measured by the CAPS, was associated with a more severe startle reaction. The magnitude of the increase in startle reactivity was moderated by parenting such that those with more positive parenting (Accepting [relative to rejecting]: b = -0.42, p < .001; Psychologically-controlling [relative to autonomy-promoting]: b = 2.96, p = .004) had significantly less reactivity across the task at higher levels of PTSD symptoms. Conclusions: Emerging adults with childhood maltreatment histories, high levels of PTSD symptoms, and who perceive present-day high-quality caregiver support may cope better with novel stressors relative to youth lacking that support, potentially translating to better psychological outcomes.
Subject(s)
Child Abuse , Stress Disorders, Post-Traumatic , Child , Adolescent , Humans , Adult , Parenting/psychology , Cross-Sectional Studies , Stress Disorders, Post-Traumatic/psychology , Fear/psychology , Child Abuse/psychologyABSTRACT
Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17-5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = -8.87 [95% CI -11.33 to -6.40], p < 0.001, ES = -0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = -8.43 [95% CI -10.98 to -5.88], p < 0.001, ES = -0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = -0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.
Subject(s)
Implosive Therapy , Nootropic Agents , Stress Disorders, Post-Traumatic , Virtual Reality , Brain-Derived Neurotrophic Factor/genetics , Cycloserine/therapeutic use , Humans , Nootropic Agents/therapeutic use , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/therapy , Treatment OutcomeABSTRACT
STUDY OBJECTIVES: Vulnerability to stress-related sleep disturbances (sleep reactivity) is an established heritable risk factor for insomnia disorder with unclear biological underpinnings. Preliminary research points to a blunted cortisol response to stress as a biological predisposition to familial risk for insomnia, but the role of cortisol response in sleep reactivity is unknown. Therefore, the current studies examined whether sleep reactivity is associated with a blunted cortisol response to two laboratory stressors among participants without insomnia. METHODS: Two community samples of adults with no lifetime history of insomnia completed the Trier Social Stress Test (N = 35) or the Cold Pressor Task (N = 34). Participants were grouped by insomnia-risk using sleep reactivity scores from the Ford Insomnia Response to Stress Test (FIRST). Physiological responses were measured via markers of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol) and autonomic nervous system (ANS; heart rate, mean arterial pressure, and salivary alpha amylase). RESULTS: Participants with high insomnia-risk (FIRST score > 18) exhibited blunted cortisol responses to both stressors. There were no group differences in ANS responses across stressors. CONCLUSIONS: Insomnia-risk as indicated by sleep reactivity is associated with blunted cortisol responses to psychosocial and physical laboratory stressors among premorbid adults without insomnia disorder. This study replicates previous research and supports a blunted cortisol response to stress as a biomarker for insomnia vulnerability that may be detected using the FIRST. Prospective research is needed to elucidate whether a blunted cortisol response to stress is one mechanism by which sleep reactive individuals may be at risk of developing insomnia.
Subject(s)
Hydrocortisone , Sleep Initiation and Maintenance Disorders , Adult , Biomarkers , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Prospective Studies , Saliva , Stress, PsychologicalABSTRACT
BACKGROUND: Survivors of childhood abuse are prone to adult insomnia, but the mechanisms for this development are poorly understood. Abuse that occurs during sensitive developmental periods might affect risk for insomnia by impacting emerging stress regulatory processes. Sleep reactivity refers to the sensitivity of the sleep system to stress and is a robust risk factor for insomnia. Recent evidence shows stress exposure itself worsens sleep reactivity, thereby increasing insomnia vulnerability. In this preliminary study, we hypothesized the association between childhood abuse experiences and adult insomnia would be mediated through greater sleep reactivity. METHODS: Community adults were recruited from the United States during the COVID-19 pandemic between June 2020 and June 2021 (N = 241, 88% female, Mage = 39, SD = 13.40). Participants completed a cross-sectional survey that included the Childhood Trauma Questionnaire, Ford Insomnia Response to Stress Test, Insomnia Severity Index, and a measure of general COVID-19 stress. RESULTS: Reporting more frequent childhood emotional, physical, or sexual abuse was associated with more severe insomnia during the COVID-19 pandemic. Only childhood emotional and physical (but not sexual) abuse histories were associated with greater sleep reactivity, which exerted an indirect effect on the relationships between these two abuse types and insomnia symptoms. These findings were robust to the effects of gender, age, and stress about the COVID-19 pandemic. CONCLUSIONS: This preliminary study suggests recurrent emotional and physical abuse in childhood might promote later insomnia through heightened sleep reactivity. Stress management interventions could be important to prevent insomnia for abuse survivors by bolstering resilience of the sleep system.
Subject(s)
COVID-19 , Child Abuse , Sleep Initiation and Maintenance Disorders , Adult , Child , Cross-Sectional Studies , Female , Humans , Male , Pandemics , Sleep/physiology , Sleep Initiation and Maintenance Disorders/epidemiologyABSTRACT
BACKGROUND: Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention. AIMS: This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans. METHODS: The study involved a randomized placebo-controlled, two-group, parallel design trial in a sample of healthy adults, age 21-55 recruited from a major metropolitan area. The experimental paradigm included a fear acquisition session followed by an extinction training session 24 hours later, and 2 hours after study drug administration. Fear extinction retention was measured 48 hours after extinction training. Participants (N = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events. RESULTS: Results indicated a significant main effect of session between extinction training and retention with no significant group differences. Significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ2 = 7.29, p = 0.007). CONCLUSION: Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) https://clinicaltrials.gov/ct2/show/NCT03181763?term = MDMA&draw = 2&rank = 9.
Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine , Stress Disorders, Post-Traumatic , Animals , Extinction, Psychological , Fear , Female , Humans , Male , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Reflex, Startle , Stress Disorders, Post-Traumatic/drug therapyABSTRACT
INTRODUCTION: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a globally significant crisis with a rapid spread worldwide, high rates of illness and mortality, a high degree of uncertainty, and a disruption of daily life across the sociodemographic spectrum. The clinically relevant psychological consequences of this catastrophe will be long-lasting and far-reaching. There is an emerging body of empirical literature related to the mental health aspects of this pandemic and this body will likely expand exponentially. The COVID-19 pandemic is an example of a historic catastrophe from which we can learn much and from which the field will need to archive, interpret, and synthesize a multitude of clinical and research observations. METHODS: In this commentary, we discuss situations and contexts in which a diagnosis of posttraumatic stress disorder (PTSD) may or may not apply within the context of diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. RESULTS: Our consensus is that a COVID-related event cannot be considered traumatic unless key aspects of DSM-5's PTSD Criterion A have been established for a specific type of COVID-19 event (e.g., acute, life-threatening, and catastrophic). CONCLUSION: The application of a more liberal interpretation of Criterion A will dilute the PTSD diagnosis, increase heterogeneity, confound case-control research, and create an overall sample pool with varying degrees of risk and vulnerability factors.
Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Diagnostic and Statistical Manual of Mental Disorders , Humans , Pandemics , SARS-CoV-2 , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/epidemiologyABSTRACT
Obstructive sleep apnea (OSA) is a respiratory condition characterized by interrupted sleep due to repeated, temporary collapse of the soft tissue of the upper airway that can lead to a cascade of physiological and psychological adverse health outcomes. The most common therapeutic interventions for OSA patients include the application of continuous positive airway pressure (CPAP) which acts to keep the airway open and, as such, provides less interrupted and more restorative sleep. Improved sleep has been linked to more efficacious treatments for psychiatric conditions most notably those that include cognitive-behavioral elements, new learning, and memory consolidation. In the current study, we investigated the acquisition, inhibition, and extinction of conditioned fear in OSA patients, before and after CPAP therapy, using an established fear-potentiated startle paradigm. Patients with OSA displayed an intact ability to acquire, inhibit, and extinguish fear prior to CPAP treatment and this ability was significantly enhanced following CPAP usage. In addition, those patients with more severe OSA, as measured by apnea-hypopnea index (AHI), were more likely to show improved fear inhibition and extinction. Lastly, we observed impairments in discrimination between reinforced and nonreinforced conditioned stimuli, in the inhibition of fear, and in fear extinction in a subset of patients with OSA and co-morbid posttraumatic stress disorder (PTSD). These data suggest that evolving treatment algorithms for PTSD should address disrupted sleep problems prior to initiation of inhibition/extinction-based exposure therapies.
Subject(s)
Extinction, Psychological , Fear/psychology , Sleep Apnea, Obstructive/psychology , Stress Disorders, Post-Traumatic/psychology , Adult , Comorbidity , Continuous Positive Airway Pressure , Female , Humans , Male , Middle Aged , Patient Acuity , Sleep Apnea, Obstructive/therapy , Stress Disorders, Post-Traumatic/etiology , Veterans/psychology , Veterans/statistics & numerical data , Young AdultABSTRACT
Posttraumatic stress disorder (PTSD) is associated with dysregulation of the neuroendocrine system, including cortisol, allopregnanolone, and pregnanolone. Preliminary evidence from animal models suggests that baseline levels of these biomarkers may predict response to PTSD treatment. We report the change in biomarkers over the course of PTSD treatment. Biomarkers were sampled from individuals participating in (1) a randomized controlled trial comparing a web-version of Prolonged Exposure (Web-PE) therapy to in-person Present-Centered Therapy (PCT) and (2) from individuals participating in a nonrandomized effectiveness study testing PE delivered in-person as part of an intensive outpatient PTSD program. We found that higher cortisol reactivity during script-driven imagery was associated with higher baseline PTSD severity and that baseline allopregnanolone, pregnanolone, and cortisol reactivity were associated with PTSD treatment responder status over the course of intensive outpatient treatment. These findings demonstrate that peripherally assessed biomarkers are associated with PTSD severity and likelihood of successful treatment outcome of PE delivered daily over two weeks. These assessments could be used to determine which patients are likely to respond to treatment and which patients require augmentation to increase the likelihood of optimal response to PTSD treatment.
Subject(s)
Biomarkers/metabolism , Implosive Therapy , Military Personnel , Neurosecretory Systems/metabolism , Stress Disorders, Post-Traumatic/therapy , Adult , Afghan Campaign 2001- , Biomarkers/analysis , Female , History, 20th Century , History, 21st Century , Humans , Hydrocortisone/analysis , Hydrocortisone/metabolism , Implosive Therapy/methods , Iraq War, 2003-2011 , Male , Middle Aged , Military Personnel/psychology , Saliva/chemistry , Saliva/metabolism , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/metabolism , Time Factors , Treatment Outcome , United StatesABSTRACT
Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences. We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (nâ¯=â¯73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, nâ¯=â¯21) to a group of carefully screened healthy controls (nâ¯=â¯35). Bayesian statistics showed no convincing evidence for a difference in physiological and subjective responses between the groups during fear acquisition, extinction learning or recall. Only the PTSD subgroup had altered startle reactions during extinction learning. Our data do not provide evidence for general differences in associative fear or extinction learning in fear-related pathologies and thereby question the diagnostic validity of the associative fear learning model of these disorders.
Subject(s)
Conditioning, Classical/physiology , Fear , Panic Disorder/physiopathology , Phobic Disorders/physiopathology , Stress Disorders, Post-Traumatic/physiopathology , Adult , Bayes Theorem , Case-Control Studies , Electromyography , Extinction, Psychological , Female , Galvanic Skin Response/physiology , Humans , Learning/physiology , Male , Middle Aged , Pupil , Reflex, Startle/physiologyABSTRACT
BACKGROUND: Attentional bias is linked to a range of mood disorders, including posttraumatic stress disorder (PTSD). The present study examined attention bias patterns in African American children exposed to trauma, in order to better understand potential risk factors for PTSD. METHODS: 31 children (ages 8-14) completed an eye-tracking task to assess gaze bias patterns while viewing pairs of emotional and neutral faces. Trauma exposure and PTSD symptoms were assessed in a subsample of children (n = 24). RESULTS: Repeated measures analysis of variance (ANOVA) results examining attention bias indices and gender showed greater attention bias toward angry faces than happy faces (p < 0.01) and toward emotional faces in males than females (p < 0.05). Correlational analyses showed attention bias toward angry faces was associated with greater levels of child trauma exposure (p < 0.05). Based on linear regression analysis, child trauma exposure accounted for 17 % of variance in attention bias toward angry versus neutral faces independent of gender or posttraumatic stress symptoms (p < 0.05). CONCLUSIONS: Trauma exposure in children is related to altered attention bias, via enhanced attention towards threatening cues. Results contribute to evidence that males and females may exhibit different attentional patterns. This study highlights the importance of additional research on attention bias patterns and prospective mental health outcomes across gender and through development.
Subject(s)
Adverse Childhood Experiences/psychology , Attentional Bias/physiology , Black or African American , Facial Recognition/physiology , Stress Disorders, Post-Traumatic/physiopathology , Adolescent , Child , Eye Movement Measurements , Facial Expression , Female , Humans , Male , Psychological Trauma/physiopathology , Psychological Trauma/psychology , Stress Disorders, Post-Traumatic/psychologyABSTRACT
Biased processing of threatening stimuli, including attention toward and away from threat, has been implicated in the development and maintenance of PTSD symptoms. Research examining theoretically-derived mechanisms through which dysregulated processing of threat may be associated with PTSD is scarce. Negative affect, a transdiagnostic risk factor for many types of psychopathology, is one potential mechanism that has yet to be examined. Thus, the present study (nâ¯=â¯92) tested the indirect effect of attention bias on PTSD via negative affect using rigorous eye-tracking methodology in a sample of urban-dwelling, trauma-exposed African-American women. We found support for the hypothesis that attention bias toward threat was indirectly associated with PTSD symptoms through increased negative affect. These results suggest that negative affect may be an important etiological process through which attention bias patterns could impact PTSD symptom severity. Implications for psychological and pharmacological therapeutic interventions targeting threat-related attention biases and negative affect are discussed.
Subject(s)
Affect , Attentional Bias , Eye Movements , Stress Disorders, Post-Traumatic/psychology , Adolescent , Adult , Black or African American/psychology , Case-Control Studies , Female , Humans , Middle Aged , Negativism , Photic Stimulation , Risk Factors , Stress Disorders, Post-Traumatic/physiopathology , Young AdultABSTRACT
After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.