Faculty Bibliography

IMPORTANCE:Anxiety disorders have a lifetime prevalence of approximately 34% in the US, are often chronic, and significantly impair quality of life and functioning. OBSERVATIONS:Anxiety disorders are characterized by symptoms that include worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Generalized anxiety disorder (6.2% lifetime prevalence), social anxiety disorder (13% lifetime prevalence), and panic disorder (5.2% lifetime prevalence) with or without agoraphobia are common anxiety disorders seen in primary care. Anxiety disorders are associated with physical symptoms, such as palpitations, shortness of breath, and dizziness. Brief screening measures applied in primary care, such as the Generalized Anxiety Disorder-7, can aid in diagnosis of anxiety disorders (sensitivity, 57.6% to 93.9%; specificity, 61% to 97%). Providing information about symptoms, diagnosis, and evidence-based treatments is a first step in helping patients with anxiety. First-line treatments include pharmacotherapy and psychotherapy. Selective serotonin reuptake inhibitors (SSRIs, eg, sertraline) and serotonin-norepinephrine reuptake inhibitors (SNRIs, eg, venlafaxine extended release) remain first-line pharmacotherapy for generalized anxiety disorder, social anxiety disorder, and panic disorder. Meta-analyses suggest that SSRIs and SNRIs are associated with small to medium effect sizes compared with placebo (eg, generalized anxiety disorder: standardized mean difference [SMD], -0.55 [95% CI, -0.64 to -0.46]; social anxiety disorder: SMD, -0.67 [95% CI, -0.76 to -0.58]; panic disorder: SMD, -0.30 [95% CI, -0.37 to -0.23]). Cognitive behavioral therapy is the psychotherapy with the most evidence of efficacy for anxiety disorders compared with psychological or pill placebo (eg, generalized anxiety disorder: Hedges g = 1.01 [large effect size] [95% CI, 0.44 to 1.57]; social anxiety disorder: Hedges g = 0.41 [small to medium effect] [95% CI, 0.25 to 0.57]; panic disorder: Hedges g = 0.39 [small to medium effect[ [95% CI, 0.12 to 0.65]), including in primary care. When selecting treatment, clinicians should consider patient preference, current and prior treatments, medical and psychiatric comorbid illnesses, age, sex, and reproductive planning, as well as cost and access to care. CONCLUSIONS AND RELEVANCE:Anxiety disorders affect approximately 34% of adults during their lifetime in the US and are associated with significant distress and impairment. First-line treatments for anxiety disorders include cognitive behavioral therapy, SSRIs such as sertraline, and SNRIs such as venlafaxine extended release.

There is some, but inconsistent, evidence to suggest that matching patient treatment preference enhances treatment engagement and outcome. The current study examined differential preferences and factors associated with treatment preference for 12-week group cognitive behavioral therapy (CBT), yoga, or stress education in 226 adults with generalized anxiety disorder (GAD; 70% female, Mean age = 33 ± 13.5). In a subsample of 165 patients who reported an intervention preference and were randomized to yoga or CBT, we further examined whether match to preferred intervention improved the primary treatment outcome (responder status on Clinical Global Impressions Scale) and engagement (dropout, homework compliance). Preferences for CBT (44%) and yoga (40%) were similar among patients. Women tended to prefer yoga (OR = 2.75, p = .01) and CBT preference was associated with higher baseline perceived stress (OR = 0.92, p = .04) and self-consciousness meta-cognitions (OR = 0.90, p = .02). Among those not matched to their preference, treatment response was higher for those receiving CBT than yoga (OR = 11.73, p = .013); there were no group differences for those matched to their treatment preference. In yoga, those who received their preference were more likely to drop than those who did not (OR = 3.02, 95% CI = [1.20, 7.58], p = .037). This was not the case for CBT (OR = 0.37, 95% CI = [0.13, 1.03], p = .076). Preference match did not predict homework compliance. Overall, results suggest that treatment preference may be important to consider to optimize outcome and engagement; however, it may vary by treatment modality. Future research incorporating preference, especially with yoga for anxiety, is aligned with personalized medicine. TRIAL REGISTRATION: clinicaltrials.gov: NCT01912287; https://clinicaltrials.gov/ct2/show/NCT01912287.

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.

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.

Losing a loved one is one of life's greatest stressors. Although most bereaved individuals navigate through a period of intense acute grief that lessens with time, approximately 10% will develop a prolonged grief condition. This review provides an overview of the course of grief and describes risk factors for developing prolonged grief disorder. The evolution of the prolonged grief disorder diagnosis, including the latest criteria sets for ICD-11 and DSM-5, as well as common comorbid conditions and differential diagnosis are discussed. Clinically useful self-report and clinician-rated measures for assessing symptom constructs and overall prolonged grief disorder severity, evidence-based psychotherapies (such as complicated grief treatment), as well as evidence about pharmacologic approaches are presented. Finally, the authors discuss important future directions, including a potential increase in prolonged grief disorder cases due to the COVID-19 pandemic.

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:: ClinicalTrials.gov identifier: NCT01179568.

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.

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".

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.