Faculty Bibliography

Post-9/11 service members may return from military service with a complicated set of symptoms and conditions, such as posttraumatic stress disorder (PTSD), depression, substance misuse, and traumatic brain injury (TBI), that interfere with reintegration and impair functioning. Although evidence-based treatments that facilitate recovery exist, their successful delivery at a sufficient dose is limited. Barriers to accessing treatment combined with challenges compiling a comprehensive treatment team further delay delivery of effective evidence-based care for PTSD, TBI, and co-occurring mental health conditions. This paper describes the development of a comprehensive, multidisciplinary, 2-week intensive day program for post-9/11 veterans with complex mental health concerns. The treatment program combines skill building groups, family education, and integrative health approaches with evidence-based individual PTSD or TBI care. Initial results from the first 132 participants were notable for a 97% completion rate, as well as statistically significant and clinically meaningful reductions in PTSD, neurobehavioral, and depression symptom severity for the 107 veterans who completed the PTSD track and the 21 who completed the TBI track. These data suggest the intensive program approach is an effective, well-tolerated model of treatment for post-9/11 veterans with PTSD and/or TBI. Future controlled studies should examine the effectiveness of this intensive model compared to standard evidence-based therapy delivery, as well as longitudinal outcomes.

Knowledge about the effect of a US service member's death on surviving family members is limited. In order to identify their grief-related health care needs, a first step is to identify the characteristics of persistent and elevated grief in a military family sample. The present study identified military family members (n = 232) bereaved more than six months who endorsed an elevated level of grief. A confirmatory factor analysis and test of measurement invariance of factor structure were used to compare the factor structure of their Inventory of Complicated Grief (ICG) responses to that of a bereaved non-military-related clinical research sample with similar grief levels. Results confirmed an equivalent five-factor structure of the ICG in both the military family sample and the clinical research sample. The similarity in factor structure was present despite differences in demographic characteristics and bereavement experiences between samples. Thus, the ICG reliably measures persistent and elevated grief in military family samples and provides grief symptom profiles that facilitates better understanding of their grief-related needs.

OBJECTIVE: Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression. METHODS: Fifty-five patients with newly diagnosed stage IV NSCLC completed self-report and clinician-administered depression assessments prior to receiving results of tumor genotyping. We measured serum levels of circulating biological markers of inflammation: IL-1beta, IL-6, TGF-alpha, and TNF-alpha. We examined differences in depression severity, MDD, and inflammatory biomarkers in patients with and without EGFR mutations. RESULTS: Patients with EGFR mutations (n=10) had lower depression severity (t[43]=2.38, p=0.03) than those without EGFR mutations (n=38) and fewer patients with EGFR mutations had concurrent MDD (2.08%) relative to those without mutations (27.08%). Patients with MDD had higher levels of TNF-alpha than those without MDD (t[40]=2.95, p=0.005). Those with EGFR mutations exhibited higher levels of TNF-alpha relative to those without EGFR mutations (t[35]=2.17, p=0.04). CONCLUSIONS: Patients with stage IV NSCLC harboring an EGFR mutation exhibited elevated proinflammatory marker TNF-alpha, yet had lower depression severity than patients without EGFR mutations. More work is warranted to examine the interaction between tumor genotyping and inflammatory cytokines in the context of depression.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, Setting, and Participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Exposures: Two-day fear conditioning and extinction paradigm. Main Outcomes and Measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (etap2 = 0.001, P = .79), where etap2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (etap2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (etap2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (etap2 = 0.137, P = .009 for conditioning and etap2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (etap2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (etap2 range between 0.111 and 0.235 and P range between 0.02 and 0.002). Conclusions and Relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

Perceived cognitive impairment is a core clinical feature of posttraumatic stress disorder (PTSD) and may be an important determinant of quality of life (QOL) in those who suffer from this disorder. Using a clinical data repository, we evaluated this hypothesis in a cross-sectional sample of U.S. military service members and veterans who served after September 11, 2001, and were seeking mental health treatment at a tertiary outpatient clinic. A consecutive series of 117 patients with a clinical diagnosis of PTSD completed a battery of questionnaires at intake, including the PTSD Checklist (Weathers, Litz, Herman, Huska, & Keane, 1993), a 4-item Cognitive Symptom subscale of the Neurobehavioral Symptom Inventory (Cicerone & Kalmar, 1995), the Depression Anxiety Stress Scale-21 (Lovibond & Lovibond, 1995), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott, Nee, Harrison, & Blumenthal, 1993). Cognitive symptom reporting was very high, even in the subgroup without a history of traumatic brain injury. In a regression analysis, cognitive symptom severity was independently associated with QOL (beta = -.204). This relationship was not explained by comorbid traumatic brain injury, but was restricted to patients with comorbid depression (beta = -.278 in the subgroup with an elevated Depression Anxiety Stress Scale-21 Depression subscale; n = 91). In conclusion, perceived cognitive impairment was common in this PTSD sample and helped to explain impairments in QOL, especially in patients with comorbid depression.

OBJECTIVES: Maladaptive cognitions related to loss are thought to contribute to development of complicated grief and are crucial to address in treatment, but tools available to assess them are limited. This paper introduces the Typical Beliefs Questionnaire (TBQ), a 25-item self-report instrument to assess cognitions that interfere with adaptation to loss. DESIGN: Study participants completed an assessment battery during their initial evaluation and again after completing treatment at 20 weeks. Test-retest reliability was assessed on a subsample of the participants who did not show change in complicated grief severity after the first 4 weeks of treatment. To examine latent structure of the TBQ, an exploratory factor analysis (EFA) was performed. SETTING: Academic medical centers in Boston, New York, Pittsburgh, and San Diego from 2010-2014. PARTICIPANTS: 394 bereaved adults who met criteria for complicated grief. MEASUREMENTS: The TBQ along with assessments of complicated grief symptoms and related avoidance, depression symptoms, functional impairment, and perceived social support. RESULTS: The TBQ exhibited good internal consistency (alpha = 0.82) and test-retest reliability (N = 105; intraclass correlation coefficient = 0.74). EFA indicated a five-factor structure: "Protesting the Death," "Negative Thoughts About the World," "Needing the Person," "Less Grief is Wrong" and "Grieving Too Much." The total score and all factors showed sensitivity to change with treatment. CONCLUSIONS: This new tool allows a clinician to quickly and reliably ascertain presence of specific maladaptive cognitions related to complicated grief, and subsequently, to use the information to aid a diagnostic assessment, to structure the treatment, and to measure treatment outcomes.

The authors compared baseline demographic characteristics, clinical features, and grief-related thoughts, feelings, and behaviors of individuals bereaved by suicide, accident/homicide and natural causes participating in a complicated grief (CG) treatment clinical trial. Severity of CG and depression and current depression diagnosis did not vary by loss type. After adjusting for baseline demographic features, time since death and relationship to the deceased, those with CG after suicide had the highest rates of lifetime depression, preloss passive suicidal ideation, self-blaming thoughts, and impaired work and social adjustment. Even among this treatment-seeking sample of research participants with CG, suicide survivors may face unique challenges.