Faculty Bibliography

Exercise is an efficacious intervention for mental and physical health, but few studies have identified the additive benefits of exercise prescriptions for those undergoing empirically supported psychosocial treatment. Behavioral activation (BA) involves completing activities to improve mood, an ideal format for exercise augmentation. The purpose of this study was to examine the credibility and exploratory effect size estimates of augmenting BA with exercise. Thirty-one sedentary, depressed patients were randomized to receive nine sessions of BA+exercise or BA+stretching over 12 weeks. Monthly assessments of depression, quality of life, distress intolerance (DI), perceived stress, and exercise were conducted. Results demonstrated strong credibility and completion rates of BA+exercise, comparable to other PA interventions. Randomization did not contribute to differential exercise between conditions; all participants engaged in more exercise over time. Similarly, all participants significantly improved on all outcomes over time. Condition differences emerged for DI and perceived stress; the exercise condition evidenced greater improvements over time. Participants who engaged in more exercise also evidenced greater and faster declines in depression. BA may be a useful strategy for improving depression and increasing exercise. Additional explicit exercise prescriptions may not be necessary to improve depression but may be helpful for DI and stress. Clinical Trials Registry (clinicaltrials.gov): NCT02176408, "Efficacy of Adjunctive Exercise for the Behavioral Treatment of Major Depression".

Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p < 0.001). Further, regular exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). When analyzing results across paradigms, sex significantly moderated the effect of exercise on BDNF levels, such that studies with more women showed less BDNF change resulting from exercise. Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans, but indicates that the magnitude of these effects may be lower in females relative to males.

BACKGROUND: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. METHODS: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. RESULTS: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. CONCLUSIONS: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation.

PURPOSE/OBJECTIVE:Breast cancer survivors may demonstrate elevated psychological distress, which can also hinder adherence to survivorship care plans. Our goal was to study heterogeneity of behavioral health and functioning in breast cancer survivors, and identify both risk and protective factors to improve targets for wellness interventions. METHODS:Breast cancer survivors (n = 187) consented to complete self-reported psychological measures and to access their medical records. Latent class analysis (LCA) was used to classify heterogeneous subpopulations based on levels of depression, post-traumatic stress, fear of cancer recurrence, cancer-related pain, and fatigue. Multinomial logistic regression and auxiliary analysis in a 3-step modeling conditional approach was used to identify characteristics of the group based on demographics, treatment history and characteristics, and current medication prescriptions. RESULTS:Three subpopulations of breast cancer survivors were identified from the LCA: a modal Resilient group (48.2%, n = 90), a Moderate Symptoms group (34%, n = 65), and an Elevated Symptoms group (n = 17%, n = 32) with clinically-relevant impairment. Results from the logistic regression indicated that individuals in the Elevated Symptoms group were less likely to have a family history of breast cancer; they were more likely to be closer to time of diagnosis and younger, have received chemotherapy and psychotropic prescriptions, and have higher BMI. Survivors in the Elevated Symptoms group were also less likely to be prescribed estrogen inhibitors than the Moderate Symptoms group. CONCLUSIONS:This study identified subgroups of breast cancer survivors based on behavioral, psychological, and treatment-related characteristics, with implications for targeted monitoring and survivorship care plans. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Results showed the majority of cancer survivors were resilient, with minimal psychological distress. Results also suggest the importance of paying special attention to younger patients getting chemotherapy, especially those without a family history of breast cancer.

Increasingly, individuals with anxiety disorders are seeking mind-body interventions (e.g., yoga), but their effectiveness is unclear. This report summarizes seven additional, secondary outcomes measuring anxiety and depression symptoms from a study of 226 adults with generalized anxiety disorder who were randomized to 12-week Kundalini Yoga, Cognitive-Behavior Therapy (CBT) or stress education (control). At post-treatment, participants receiving CBT displayed significantly lower symptom severity, compared to those in the control group, on 6 of the 7 measures. Participants who received Yoga (vs. those in the control group) displayed lower symptom severity on 3 of the 7 measures. No significant differences were detected between participants receiving CBT vs those receiving Yoga. At the 6-month follow-up, participants from the CBT continued to display lower symptoms than the control group.

Most U.S. adults, even more so those with psychiatric conditions like obsessive-compulsive disorder (OCD), do not engage in the recommended amount of physical activity (PA), despite the wide array of physical and mental health benefits associated with exercise. Therefore, it is essential to identify mechanistic factors that drive long-term exercise engagement so they can be targeted. Using the science of behavior change (SOBC) framework, this study examined potential predictors of long-term exercise engagement as a first step towards identifying modifiable mechanisms, in individuals with OCD, such as PA enjoyment, positive or negative affect, and behavioral activation. Fifty-six low-active patients (mean age = 38.8 ± 13.0, 64% female) with a primary diagnosis of OCD were randomized to either aerobic exercise (AE; n = 28) or health education (HE; n = 28), and completed measures of exercise engagement, PA enjoyment, behavioral activation, and positive and negative affect at baseline, postintervention, and 3-, 6-, and 12-month follow-up. Significant predictors of long-term exercise engagement up to 6-months postintervention were baseline PA (Estimate = 0.29, 95%CI [0.09, 0.49], p = .005) and higher baseline PA enjoyment (Estimate = 1.09, 95%CI [0.30, 1.89], p = .008). Change in PA enjoyment from baseline to postintervention was greater in AE vs. HE, t(44) = -2.06, p = .046, d = -0.61, but endpoint PA enjoyment did not predict follow-up exercise engagement above and beyond baseline PA enjoyment. Other hypothesized potential mechanisms (baseline affect or behavioral activation) did not significantly predict exercise engagement. Results suggest that PA enjoyment may be an important modifiable target mechanism for intervention, even prior to a formal exercise intervention. Next steps aligned with the SOBC framework are discussed, including examining intervention strategies to target PA enjoyment, particularly among individuals with OCD or other psychiatric conditions, who may benefit most from long-term exercise engagement's effects on physical and mental health.

As many individuals experience potentially traumatic or stressful life events, understanding factors that are likely to promote resilience is imperative. Given the demonstrated efficacy of exercise for depression treatment, we examined if exercise buffers against the risk of developing psychiatric symptoms following life stressors. 1405 participants (61% female) from a longitudinal panel cohort experienced disability onset (43%), bereavement (26%), heart attack (20%), divorce (11%), and job loss (3%). They reported time spent exercising and depressive symptoms (Center for Epidemiologic Studies Depression scale) across three time points collected in two-year intervals: T0 (pre-stressor), T1 (acutely post-stressor), and T2 (post-stressor). Participants were classified in previously identified heterogeneous depression trajectories pre-to post-life stressor: resilient (69%), emerging (11.5%), chronic (10%), and improving (9.5%). Multinomial logistic regression found that more T0 exercise predicted likelihood of classification in resilient versus other groups (all p <.02). Controlling for covariates, only the higher likelihood of classification in resilient versus improving remained (p =.03). Follow-up repeated measures general linear model (GLM) assessed whether trajectory was associated with exercise at each time, controlling for covariates. GLM indicated significant within-subjects effects for time (p =.016, partial η² = 0.003) and time*trajectory (p =.020, partial η² = 0.005) on exercise and significant between-subjects effects of trajectory (p <.001, partial η² = 0.016) and all covariates. The resilient group showed consistent high exercise levels. The improving group had consistent moderate exercise. The emerging and chronic groups were associated with lower exercise post-stressor. Pre-stressor exercise may buffer against depression and ongoing exercise may be associated with lower depression levels following a major life stressor.

As many individuals experience potentially traumatic or stressful life events, understanding factors that are likely to promote resilience is imperative. Given the demonstrated efficacy of exercise for depression treatment, we examined if exercise buffers against the risk of developing psychiatric symptoms following life stressors. 1405 participants (61% female) from a longitudinal panel cohort experienced disability onset (43%), bereavement (26%), heart attack (20%), divorce (11%), and job loss (3%). They reported time spent exercising and depressive symptoms (Center for Epidemiologic Studies Depression scale) across three time points collected in two-year intervals: T0 (pre-stressor), T1 (acutely post-stressor), and T2 (post-stressor). Participants were classified in previously identified heterogeneous depression trajectories pre- to post-life stressor: resilient (69%), emerging (11.5%), chronic (10%), and improving (9.5%). Multinomial logistic regression found that more T0 exercise predicted likelihood of classification in resilient versus other groups (all p<.02). Controlling for covariates, only the higher likelihood of classification in resilient versus improving remained (p=.03). Follow-up repeated measures general linear model (GLM) assessed whether trajectory was associated with exercise at each time, controlling for covariates. GLM indicated significant within-subjects effects for time (p=.016, partial η²=.003) and time*trajectory (p=.020, partial η²=.005) on exercise and significant between-subjects effects of trajectory (p<.001, partial η²=.016) and all covariates. The resilient group showed consistent high exercise levels. The improving group had consistent moderate exercise. The emerging and chronic groups were associated with lower exercise post-stressor. Pre-stressor exercise may buffer against depression and ongoing exercise may be associated with lower depression levels following a major life stressor.

Trauma-informed beliefs often decrease during posttraumatic stress disorder (PTSD) treatment. This may also extend to anxiety sensitivity (AS), defined as a fear of anxiety-related sensations and beliefs that anxiety is dangerous and/or intolerable. However, little is known about how AS changes during exposure-based and psychopharmacological PTSD treatments. Further, high AS may be a risk factor for diminished PTSD symptom improvement and increased treatment dropout. To better understand how AS impacts and is impacted by PTSD treatment, we conducted a secondary analysis of a randomized clinical trial with a sample of 223 veterans (87.0% male, 57.5% White) with PTSD from four U.S. sites. Veterans were randomized to receive prolonged exposure (PE) plus placebo (n = 74), sertraline plus enhanced medication management (n = 74), or PE plus sertraline (n = 75). Veterans answered questions about PTSD symptoms and AS at baseline and 6-, 12-, 24-, 36-, and 52-week follow-ups. High baseline AS was related to high levels of PTSD severity at 24 weeks across all conditions, β = .244, p = .013, but did not predict dropout from exposure-based, β = .077, p = .374, or psychopharmacological therapy, β = .009, p = .893. AS also significantly decreased across all three treatment arms, with no between-group differences; these reductions were maintained at the 52-week follow-up. These findings suggest that high AS is a risk factor for attenuated PTSD treatment response but also provide evidence that AS can be improved by both PE and an enhanced psychopharmacological intervention for PTSD.