Faculty Bibliography

OBJECTIVE:Suffering associated with complicated grief (CG) is profound. Because suicide loss survivors are susceptible to developing CG, identifying effective treatments for suicide loss survivors with CG is a high priority. This report provides data on the acceptability and effectiveness of antidepressant medication and complicated grief therapy (CGT), a CG-targeted psychotherapy, for suicide loss survivors with CG identified by an Inventory of Complicated Grief score ≥ 30. METHODS:This is a secondary analysis of data collected from March 2010 to September 2014 for a 4-site, double-blind, placebo-controlled randomized trial comparing the effectiveness of antidepressant medication alone or in combination with CGT for participants with CG (score ≥ 30 on the Inventory of Complicated Grief) who were bereaved by suicide (SB; n = 58), accident/homicide (A/H; n = 74), or natural causes (NC; n = 263). Using mode of death as a grouping factor, we evaluated acceptability of treatments by comparing 12-week medication and 16-session CGT completion; we evaluated effectiveness by comparing response at week 20, defined by a score of 1 or 2 on the Complicated Grief Clinical Global Impressions-Improvement scale (CG-CGI-I), and additional secondary response measures. RESULTS:Among participants receiving medication alone, SB medication completion rates (36%) were lower than rates for A/H (54%) and NC (68%; χ² = 11.76, P < .01). SB medication completion rates were much higher for SB individuals receiving CGT (82%; χ² = 12.45, P < .001) than for SB individuals receiving medication alone. CGT completion rates were similar in the 3 groups (SB = 74%, A/H = 64%, NC = 77%; χ² = 2.48, P = .29). For SB participants receiving CGT, CG-CGI-I response rates were substantial (64%), but lower compared to the other groups (A/H = 93%, NC = 84%; χ² = 8.00, P < .05). However, on all other outcomes, changes from baseline for SB participants were comparable to those for A/H and NC participants, including number and severity of grief symptoms, suicidal ideation, and grief-related impairment, avoidance, and maladaptive beliefs. CONCLUSIONS:These results raise concern about the acceptability of medication alone as a treatment for complicated grief in treatment-seeking suicide-bereaved adults. In contrast, CGT is an acceptable and promising treatment for suicide-bereaved individuals with complicated grief. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT01179568.

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.

Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.

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.