Faculty Bibliography

BACKGROUND:Telemedicine is a strategy for overcoming barriers to access evidence-based psychotherapy. Digital modalities that operate outside session-based treatment formats, such as ongoing two-way messaging, may further address these challenges. However, no study to date has established suitability criteria for this medium. METHODS:A large outpatient sample (n = 10,718) engaged in daily messaging with licensed clinicians from a telemedicine provider. Patients consisted of individuals from urban and rural settings in all 50 states of the US, who signed up to the telemedicine provider. Using a longitudinal design, symptoms changes were observed during a 12 week treatment course. Symptoms were assessed from baseline every three weeks using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder (GAD-7) for anxiety. Demographics and engagement metrics, such as word count for both patients and therapists, were also assessed. Growth mixture modeling was used to tease apart symptoms trajectories, and identify predictors of treatment response. RESULTS:Two subpopulations had GAD-7 and PHQ-9 remission outcomes (Recovery and Acute Recovery, 30.7% of patients), while two others showed amelioration of symptoms (Depression and Anxiety Improvement, 36.9% of patients). Two subpopulations experienced no changes in symptoms (Chronic and Elevated Chronic, 32.4% of patients). Higher use of written communication, patient characteristics, and engagement metrics reliably distinguished patients with the greatest level of remission (Recovery and Acute Recovery groups). CONCLUSIONS:Remission of depression and anxiety symptoms was observed during delivery of psychotherapy through messaging. Improvement rates were consistent with face-to-face therapy, suggesting the suitability of two-way messaging psychotherapy delivery. Characteristics of improving patients were identified and could be used for treatment recommendation. These findings suggest the opportunity for further research, to directly compare messaging delivery with a control group of treatment as usual. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT03699488, Retrospectively Registered October 8, 2018.

PTSD is associated with abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity. This includes enhanced HPA axis negative feedback, attenuated cortisol awakening response, and attenuated cortisol response to personal trauma script. Whether HPA axis function predicts treatment response or treatment related symptom reduction in PTSD remains unclear. In addition, the relative effects of different treatment modalities (i.e., medication and psychotherapy) on HPA axis is unclear. To address this gap in knowledge, the PROGrESS study examined cortisol awakening response across treatment in Veterans with chronic PTSD randomized to receive Prolonged Exposure + Placebo (PE + PLB), Sertraline + PE (SERT + PE) or Sertraline + Enhanced Medication Management (SERT + EMM). Salivary cortisol awakening response (CAR) was assessed at baseline, mid-treatment (week 6 and 12), post-treatment (week 24) and follow-up (week 36 and 52). Among males at baseline, combat veterans with PTSD showed lower CAR Area Under the Curve Increase (AUCi; M = 3.15, SD = 9.57) than Combat controls (M = 7.63, SD = 9.07; p = .02), demonstrating combat veterans with PTSD have a less responsive system than combat controls. Higher PTSD severity was also related to lower CAR AUCi (r = -0.52, p = .03). When controlling for PTSD severity, higher baseline CAR AUCi was related to attenuated reduction in PTSD and lower likelihood of high treatment response over treatment (z = -2.06, p = .04).

BACKGROUND:Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. METHOD/METHODS:We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053). RESULTS:Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. CONCLUSIONS:This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Studies show that attentional bias towards threat is a key maintenance factor for panic disorder (PD). Attentional bias may be an important mechanism of symptom reduction, and thus, a useful target for optimizing outcomes. The current study examined whether an attention bias modification (ABM) task enhanced CBT outcomes. Multiple methods for assessing PD were used, including physiological measurement and clinician-rated assessment. METHODS:Adults with panic disorder (N = 24) received seven sessions of CBT with either ABM or sham attention tasks. Psychophysiological reaction to a loud tones startle paradigm was assessed before and after treatment. RESULTS:Across both groups, panic symptom severity decreased with CBT. The ABM group showed greater reductions in PD symptoms compared to the placebo group. Notably, however, changes in attentional bias were not associated with symptom reductions across groups. No significant group differences on psychophysiological assessment were observed. LIMITATIONS/CONCLUSIONS:This study is limited by the small sample size, which rendered our power to investigate mediators and moderators insufficient. More research is needed to validate the effect of attention bias modification on attentional bias to threat. CONCLUSIONS:This pilot study suggests that future research should investigate attentional bias in conjunction with CBT. A larger sample would provide opportunity to further investigate the mechanisms through which ABM works, along with potential moderating factors and the use of psychophysiological measurements in panic disorder.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) commonly co-occur in combat veterans, and this comorbidity has been associated with higher levels of distress and more social and economic costs compared to one disorder alone. In a secondary analysis of a multisite randomized controlled trial of a sample of veterans with combat-related PTSD, we examined the associations among pre-, peri-, and postdeployment adversity, social support, and clinician-diagnosed comorbid MDD. Participants completed the Deployment Risk and Resilience Inventory and the Beck Depression Inventory-II as well as structured clinical interviews for diagnostic status. Among 223 U.S. veterans of the military operations in Iraq and Afghanistan (86.9% male) with primary combat-related PTSD, 69.5% had current comorbid MDD. After adjustment for sex, a linear regression model indicated that more concerns about family disruptions during deployment, f² = 0.065; more harassment during deployment, f² = 0.020; and lower ratings of postdeployment social support, f² = 0.154, were associated with more severe self-reported depression symptoms. Interventions that enhance social support as well as societal efforts to foster successful postdeployment reintegration are critical for reducing the mental health burden associated with this highly prevalent comorbidity in veterans with combat-related PTSD.

We report on a novel 2-week intensive outpatient treatment program (IOP) for 24 widows bereaved by the suicide death of their veteran spouse. We targeted symptoms of posttraumatic stress disorder (PTSD) and complicated grief (CG) concurrently in three separate cohorts. All patients either witnessed the death or discovered the body of their deceased partner, who was a veteran of the United States military. PTSD, CG, and depression symptom severity decreased significantly from pre- to post-treatment, with effect sizes of 0.85, 1.21, and 1.35, respectively. These outcomes provide preliminary support for an IOP to treat co-occurring PTSD and CG among widowed survivors of veteran suicide.

Although mindfulness-based interventions (MBIs) have garnered empirical support for a wide range of psychological conditions, the psychological processes that mediate the relationship between MBIs and subsequent symptomatic improvement are less well-understood. In the present study we sought to examine, for the first time, the relationship between mindfulness, negative interpretation bias as measured by the homophone task, and anxiety among adults with Generalized Anxiety Disorder (GAD). Forty-two individuals with GAD completed measures of mindfulness, interpretation bias, and anxiety before and after treatment with Mindfulness-based Stress Reduction (MBSR). Contrary to prior research, we did not find evidence of an indirect relationship between baseline levels of mindfulness and anxiety via negative interpretation bias. MBSR did result in significant reductions in negative interpretation bias from baseline to post-treatment; however, we did not find evidence of an indirect relationship between changes in mindfulness and changes in anxiety via changes in interpretation bias. Taken together, these results provide minimal support for the hypothesized relationship between mindfulness, negative interpretation bias, and anxiety among adults with GAD. Limitations and specific suggestions for further inquiry are discussed.

Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy and psychotherapy are first-line treatment strategies for anxiety disorders, many patients are reluctant to take psychiatric medication, and many prefer to avoid any kind of mental health treatment due to stigma or distrust of traditional medical care. We present the trial protocol for the first study comparing first-line medication treatment with Mindfulness-Based Stress Reduction (MBSR), a popular mindfulness meditation training program, for the treatment of anxiety disorders. We will use a non-inferiority, comparative effectiveness trial design, in which individuals with diagnosed anxiety disorders will be randomized to either pharmacotherapy with escitalopram or MBSR for 8 weeks of treatment. Treatment outcome will be based on gold standard symptom severity measures assessed by trained independent evaluators blind to treatment allocation. Secondary outcomes will include key symptom and function measures, as well as tolerability and satisfaction with treatment. Findings will provide crucial information to inform decision making about the relative benefits of MBSR versus a first line medication for anxiety disorders by patients, medical care providers, healthcare insurers and other stakeholders.

Importance/UNASSIGNED:The Research Domain Criteria project of the National Institute of Mental Health aims to guide neuropsychiatry toward precision medicine. Its inception was partly in response to the overlap of clinical manifestations between different DSM-IV diagnoses within a category. For example, anxiety disorders comprise a DSM-IV category that includes diagnoses that differ from each other but are all characterized by dysregulated fear levels. Whether DSM-IV-based and Research Domain Criteria-based analytic approaches provide distinct or similar information with regard to the fear circuitry of individuals with anxiety disorders has not been directly tested. Objective/UNASSIGNED:To use a threat conditioning and extinction protocol to conduct categorical (DSM-IV-based) and dimensional (Research Domain Criteria-based) assessments of psychophysiological, neural, and psychometric responses in individuals with and without anxiety disorders. Design, Setting, and Participants/UNASSIGNED:This cross-sectional study was conducted at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston between March 2013 and May 2015. Functional magnetic resonance imaging was used to assess psychophysiological, neural, and psychometric responses among adults aged 18 to 65 years with specific phobia, generalized anxiety disorder, social anxiety disorder, and panic disorder as well as a control group of adults without anxiety disorders. Data were analyzed between May 2018 and April 2019. Exposures/UNASSIGNED:A 2-day threat conditioning and extinction protocol. Main Outcomes and Measures/UNASSIGNED:Skin conductance responses and blood oxygenated level-dependent responses were measured during the threat and extinction protocol. The categorical analysis was performed by grouping participants based on their primary DSM-IV diagnosis. The dimensional analysis was performed by regrouping participants, irrespective of their diagnoses, based on their skin conductance responses to shock delivery during threat conditioning. Results/UNASSIGNED:This cross-sectional study of 114 adults aged 18 to 65 years included 93 participants (34 men and 59 women; mean [SD] age, 29.7 [11.1] years) with at least 1 anxiety disorder (specific phobia, generalized anxiety disorder, social anxiety disorder, or panic disorder) and 21 participants (11 men and 10 women) without an anxiety disorder. The categorical DSM-IV-based approach indicated that all anxiety disorder groups exhibited hypoactivation in the ventromedial prefrontal cortex during extinction recall (ηp2 = 0.15; P = .004). The Research Domain Criteria-based approach revealed that higher arousal to the unconditioned stimulus was associated with higher threat responses during extinction recall (for skin conductance responses, ηp2 = 0.21; P = .01 and in functional magnetic resonance imaging results, ηp2 = 0.12; P = .02). The direct comparison of DSM-IV-based vs Research Domain Criteria-based results did not yield significant findings (ηp2 values ranged from 0.02 to 0.078; P values ranged from .09 to .98), suggesting no overlap between the approaches. Conclusions and Relevance/UNASSIGNED:The data obtained from both approaches indicated complementary yet distinct findings. The findings highlight the validity and importance of using both categorical and dimensional approaches to optimize understanding of the etiology and treatment of anxiety symptoms.