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Efficacy evaluation of exercise as an augmentation strategy to brief behavioral activation treatment for depression: a randomized pilot trial

Szuhany, Kristin L; Otto, Michael W
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 ( NCT02176408, "Efficacy of Adjunctive Exercise for the Behavioral Treatment of Major Depression".
PMID: 31357916
ISSN: 1651-2316
CID: 4002272

A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor

Szuhany, Kristin L; Bugatti, Matteo; Otto, Michael W
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.
PMID: 25455510
ISSN: 1879-1379
CID: 4002202


Otto, Michael W; Pollack, Mark H; Dowd, Sheila M; Hofmann, Stefan G; Pearlson, Godfrey; Szuhany, Kristin L; Gueorguieva, Ralitza; Krystal, John H; Simon, Naomi M; Tolin, David F
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.
PMID: 27315514
ISSN: 1520-6394
CID: 2724742

Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder

Stein, Murray B; Jain, Sonia; Simon, Naomi M; West, James C; Marvar, Paul J; Bui, Eric; He, Feng; Benedek, David M; Cassano, Paolo; Griffith, James L; Howlett, Jonathan; Malgaroli, Matteo; Melaragno, Andrew; Seligowski, Antonia V; Shu, I-Wei; Song, Suzan; Szuhany, Kristin; Taylor, Charles T; Ressler, Kerry J
BACKGROUND:Evidence-based pharmacological treatments for posttraumatic stress disorder (PTSD) are few and of limited efficacy. Previous work suggests that angiotensin type 1 receptor inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the angiotensin type 1 receptor antagonist losartan, an antihypertensive drug, repurposed for the treatment of PTSD. METHODS:A randomized controlled trial was conducted for 10 weeks in 149 men and women meeting DSM-5 PTSD criteria. Losartan (vs. placebo) was flexibly titrated from 25 to 100 mg/day by week 6 and held at highest tolerated dose until week 10. Primary outcome was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) change score at 10 weeks from baseline. A key secondary outcome was change in CAPS-5 associated with a single nucleotide polymorphism of the ACE gene. Additional secondary outcomes included changes in the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9, and proportion of responders with a Clinical Global Impressions-Improvement scale of "much improved" or "very much improved." RESULTS:Both groups had robust improvement in PTSD symptoms, but there was no significant difference on the primary end point, CAPS-5 measured as week 10 change from baseline, between losartan and placebo (mean change difference, 0.9, 95% confidence interval, -3.2 to 5.0). There was no significant difference in the proportion of Clinical Global Impressions-Improvement scale responders for losartan (58.6%) versus placebo (57.9%), no significant differences in changes in PTSD Checklist for DSM-5 or Patient Health Questionnaire-9, and no association between ACE genotype and CAPS-5 improvement on losartan. CONCLUSIONS:At these doses and durations, there was no significant benefit of losartan compared with placebo for the treatment of PTSD. We discuss implications for failure to determine the benefit of a repurposed drug with strong a priori expectations of success based on preclinical and epidemiological data.
PMID: 34275593
ISSN: 1873-2402
CID: 4947782

Barriers and engagement in breast cancer survivorship wellness activities

Szuhany, Kristin L; Malgaroli, Matteo; Riley, Gabriella; Miron, Carly D; Suzuki, Rebecca; Park, Jae Hyung; Rosenthal, Jane; Chachoua, Abraham; Meyers, Marleen; Simon, Naomi M
PURPOSE/OBJECTIVE:Breast cancer survivors may be at risk for increased rates of emotional distress and poorer quality of life. Survivorship care plans (SCPs) promoting wellness activities may support well-being; however, survivors may not receive or engage in their SCPs. This study aimed to assess receipt and participation in SCP activities as well as barriers to engagement amongst breast cancer survivors. METHODS:Breast cancer survivors (n = 187; 99% female, Mean age = 57.7) consented and completed self-reported assessments of SCP recommendations, engagement and interest in wellness activities, and potential barriers to engagement. RESULTS:A minority of participants recalled receiving an SCP (21%). The most physician recommended (62%) and completed (53%) activity was exercise. Interest in adding other wellness activities to the SCP was high, with reported interest levels of approximately 50% for several activities (e.g., mind body, nutrition, psychotherapy interventions). Fully half reported that having a physician-designed plan would influence participation in activities. The most common reported barriers to SCP activity engagement were lack of time (82%), work/school (65%), and lack of information (65%). CONCLUSION/CONCLUSIONS:Few survivors recalled receiving a formal SCP, and lack of information about wellness activities was a commonly reported barrier to participation. Interest in wellness activities was generally high and may indicate the need for more formal prescription or motivation enhancement techniques to promote SCP engagement. There may be a clinical need to emphasize SCP recommendations to enhance recall and increase engagement in wellness activities that may reduce psychological distress and improve quality of life.
PMID: 34095986
ISSN: 1573-7217
CID: 4899592

Posttraumatic Distress Symptoms and Their Response to Treatment in Adults With Prolonged Grief Disorder

Na, Peter J; Adhikari, Samrachana; Szuhany, Kristin L; Chen, Alan Z; Suzuki, Rebecca R; Malgaroli, Matteo; Robinaugh, Donald J; Bui, Eric; Mauro, Christine; Skritskaya, Natalia A; Lebowitz, Barry D; Zisook, Sidney; Reynolds, Charles F; Shear, M Katherine; Simon, Naomi M
OBJECTIVE:Posttraumatic stress disorder and prolonged grief disorder (PGD) arise following major life stressors and may share some overlapping symptomatology. This study aimed to examine the presence and response to treatment of posttraumatic stress symptoms (PTSS) in bereaved adults with a primary diagnosis of PGD. METHODS:A randomized controlled trial of 395 adults with PGD (defined as an Inventory of Complicated Grief score ≥ 30 plus confirmation on structured clinical interview) randomly assigned participants to either complicated grief treatment (CGT) with citalopram, CGT plus placebo, citalopram, or placebo between March 2010 and September 2014. This secondary analysis examined the presence of PTSS (per the Davidson Trauma Scale) at baseline and change in PTSS with treatment using longitudinal mixed-effects regression and examined the role of violent compared to nonviolent deaths (loss type). RESULTS:High levels of PTSS were present at baseline, regardless of loss type, and were associated with increased functional impairment (P < .001). CGT with placebo demonstrated efficacy for PTSS compared to placebo in both threshold (OR = 2.71; 95% CI, 1.13-6.52; P = .026) and continuous (P < .001; effect size d = 0.47) analyses, and analyses were suggestive of a greater effect for CGT plus citalopram compared to citalopram alone (threshold analysis: OR = 2.84; 95% CI, 1.20-6.70; P = .017; continuous analysis: P = .053; d = 0.25). In contrast, citalopram did not differ from placebo, and CGT plus citalopram did not differ from CGT plus placebo. CONCLUSIONS:Bereavement-related PTSS are common in bereaved adults with PGD in the context of both violent and nonviolent death and are associated with poorer functioning. CGT shows efficacy for PTSS, while the antidepressant citalopram does not. TRIAL REGISTRATION:: identifier: NCT01179568.
PMID: 34000119
ISSN: 1555-2101
CID: 4876702

Park Proximity and Use for Physical Activity among Urban Residents: Associations with Mental Health

Orstad, Stephanie L; Szuhany, Kristin; Tamura, Kosuke; Thorpe, Lorna E; Jay, Melanie
Increasing global urbanization limits interaction between people and natural environments, which may negatively impact population health and wellbeing. Urban residents who live near parks report better mental health. Physical activity (PA) reduces depression and improves quality of life. Despite PA's protective effects on mental health, the added benefit of urban park use for PA is unclear. Thus, we examined whether park-based PA mediated associations between park proximity and mental distress among 3652 New York City residents (61.4% 45 + years, 58.9% female, 56.3% non-white) who completed the 2010-2011 Physical Activity and Transit (PAT) random-digit-dial survey. Measures included number of poor mental health days in the previous month (outcome), self-reported time to walk to the nearest park from home (exposure), and frequency of park use for sports, exercise or PA (mediator). We used multiple regression with bootstrap-generated 95% bias-corrected confidence intervals (BC CIs) to test for mediation by park-based PA and moderation by gender, dog ownership, PA with others, and perceived park crime. Park proximity was indirectly associated with fewer days of poor mental health via park-based PA, but only among those not concerned about park crime (index of moderated mediation = 0.04; SE = 0.02; 95% BC CI = 0.01, 0.10). Investment in park safety and park-based PA promotion in urban neighborhoods may help to maximize the mental health benefits of nearby parks.
PMID: 32645844
ISSN: 1660-4601
CID: 4518012

Assessing BDNF as a mediator of the effects of exercise on depression

Szuhany, Kristin L; Otto, Michael W
Brain-derived neurotrophic factor (BDNF) is associated with neuronal growth and reduced BDNF has been implicated in depression. A recent meta-analysis documented reliable effects of exercise on BDNF levels (Szuhany et al., 2015); although, few studies included participants with mental health conditions. In this study, we examine whether increased exercise was associated with enhanced BDNF response in depressed patients, and whether this change mediated clinical benefits. A total of 29 depressed, sedentary participants were randomized to receive either behavioral activation (BA) plus an exercise or stretching prescription. Blood was collected prior to (resting BDNF levels) and following an exercise test (pre-to post-exercise BDNF change) at four points throughout the study. Participants also completed depression and exercise assessments. BDNF increased significantly across all assessment points (p < 0.001, d = 0.83). Changes in BDNF from pre-to post-exercise were at a moderate effect for the interaction of exercise and time which did not reach significance (p = 0.13, d = 0.53), with a similar moderate, non-significant effect for resting BDNF levels (p = 0.20, d = 0.49). Contrary to hypotheses, change in resting BDNF or endpoint change in BDNF was not associated with changes in depression. In an intervention that included active treatment (BA), we could not verify an independent predictive effect for changes in BDNF across the trial. Overall, this study adds to the literature showing reliable effects of acute exercise on increasing BDNF and extends this research to the infrequently studied depressed population, but does not clarify the mechanism behind exercise benefits for depression. CLINICAL TRIALS REGISTRY (CLINICALTRIALS.GOV): NCT02176408, "Efficacy of Adjunctive Exercise for the Behavioral Treatment of Major Depression".
PMID: 32065946
ISSN: 1879-1379
CID: 4312042

Catching As and Zs: poor sleep quality predicts failures to increase studying time

Patten, Elijah A; Kredlow, M Alexandra; Szuhany, Kristin L; Keshishian, Ani C; Otto, Michael W
OBJECTIVE:We examined the association between sleep quality and academic performance by attending to university students' self-defined goals to increase studying behaviors over a four-week period. METHODS:We evaluated this association in 100 undergraduates, who self-elected to change their studying behaviors and were randomly assigned to one of three interventions (action planning, dissonance-based, or reflection). RESULTS:We found a negative association between the Pittsburgh Sleep Quality Index (PSQI) at baseline and subsequent studying time over the next four weeks, reflecting a small to medium effect size (partial r = .21). Depressive symptoms did not mediate the predictive influence of sleep quality on studying behavior. Intervention type did not influence the association between sleep quality and studying time. CONCLUSIONS:The predictive significance of sleep quality, in the context of the failure of effects for the randomized interventions, underscores the potential for intervening with sleep as part of efforts to improve academic behaviors.
PMID: 31676201
ISSN: 2352-7226
CID: 4184352

Impact of sleep on complicated grief severity and outcomes

Szuhany, Kristin L; Young, Allison; Mauro, Christine; Garcia de la Garza, Angel; Spandorfer, Julia; Lubin, Rebecca; Skritskaya, Natalia A; Hoeppner, Susanne S; Li, Meng; Pace-Schott, Ed; Zisook, Sidney; Reynolds, Charles F; Shear, M Katherine; Simon, Naomi M
BACKGROUND:Complicated grief (CG) is characterized by persistent, impairing grief after losing a loved one. Little is known about sleep disturbance in CG. Baseline prevalence of subjective sleep disturbance, impact of treatment on sleep, and impact of mid-treatment sleep on CG and quality of life outcomes were examined in adults with CG in secondary analyses of a clinical trial. METHODS:Patients with CG (n = 395, mean age =53.0; 78% female) were randomized to CGT+placebo, CGT+citalopram (CIT), CIT, or placebo. Subjective sleep disturbance was assessed by a grief-anchored sleep item (Pittsburgh Sleep Quality Index: PSQI-1) and a four-item sleep subscale of the Quick Inventory of Depressive Symptomatology (QIDS-4). Sleep disturbance was quantified as at least one QIDS-4 item with severity ≥2 or grief-related sleep disturbance ≥3 days a week for PSQI-1. Outcomes included the Inventory of Complicated Grief (ICG), Work and Social Adjustment Scale (WSAS), and Clinical Global Impressions Scale. RESULTS:Baseline sleep disturbance prevalence was 91% on the QIDS-4 and 46% for the grief-anchored PSQI-1. Baseline CG severity was significantly associated with sleep disturbance (QIDS-4: p = .015; PSQI-1: p = .001) after controlling for comorbid depression and PTSD. Sleep improved with treatment; those receiving CGT+CIT versus CIT evidenced better endpoint sleep (p = .027). Mid-treatment QIDS-4 significantly predicted improvement on outcome measures (all p < .01), though only WSAS remained significant after adjustment for mid-treatment ICG (p = .02). CONCLUSIONS:Greater CG severity is associated with poorer sleep beyond PTSD and depression comorbidity. Additional research including objective sleep measurement is needed to optimally elucidate and address sleep impairment associated with CG.
PMID: 31916662
ISSN: 1520-6394
CID: 4257522