The loss of a fellow service member: Complicated grief in post-9/11 service members and veterans with combat-related posttraumatic stress disorder.

Bereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 post-9/11, when service members and veterans with combat-related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; n = 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, n = 39) compared to those bereaved who did not (16.92%, n = 11; OR = 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, trauma-related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combat-related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.

Inflammatory cytokines in major depressive disorder: A case-control study.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

Validation of electronic health record phenotyping of bipolar disorder cases and controls.

OBJECTIVE: The study was designed to validate use of electronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects. METHOD: EHR data were obtained from a health care system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype diagnoses was calculated against diagnoses from direct semistructured interviews of 190 patients by trained clinicians blind to EHR diagnosis. RESULTS: The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR-classified control subject received a diagnosis of bipolar disorder on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based classifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses. CONCLUSIONS: Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.

Anxiety sensitivity in bereaved adults with and without complicated grief.

Complicated grief (CG) is a bereavement-specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (AS; i.e., the fear of anxiety-related sensations) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms.

Complicated grief symptoms in anxiety disorders: prevalence and associated impairment.

BACKGROUND: Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD. METHODS: Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively. RESULTS: Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (ß = -0.140, P = 0.023) and greater impairment (ß = 0.141, P = 0.035) among individuals with AD. CONCLUSIONS: Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.

Pharmacological approaches to the treatment of complicated grief: rationale and a brief review of the literature.

Complicated grief (CG) is a common and often under-acknowledged cause of profound impairment experienced after the loss of a loved one. Although both clinical and basic research suggests that pharmacological agents might be of use in the treatment of CG, research on pharmacological approaches to this condition is still scarce. Three open-label trials and one randomized trial on bereavement-related depression suggest that tricyclic antidepressants may be effective, although they may be more efficacious for depressive symptoms than for grief-specific symptoms. Four open-label trials (total number of participants, 50) of selective serotonin reuptake inhibitors (SSRIs) have yielded results, providing very preliminary support that they might be effective in the treatment of CG, both as a standalone treatment and in conjunction with psychotherapeutic interventions. These more recent studies have shown an effect on both depression and grief-specific scales. Furthermore, therapeutic interventions for CG may be more effective in conjunction with SSRI administration. Given the small number of pharmacological studies to date, there is a need for randomized trials to test the potential efficacy of pharmacological agents in the treatment of CG.

Diurnal rhythm of cone opsin expression in the teleost fish Haplochromis burtoni.

The biochemical and morphological specializations of rod and cone photoreceptors reflect their roles in sight. The apoprotein opsin, which converts photons into chemical signals, functions at one end of these highly polarized cells, in the outer segment. Previous work has shown that the mRNA of rod opsin, the opsin specific to rods, is renewed in the outer segment with a diurnal rhythm in the retina of the teleost fish Haplochromis burtoni. Here we show that in the same species, all three cone opsin mRNAs (blue, green, and red) also have a diurnal rhythm of expression. Quantitative real-time polymerase chain reaction (PCR) with primer pairs specific for the cone photoreceptor opsin subtypes was used to detect opsin mRNA abundance in animals sacrificed at 3-h intervals around the clock. All three cone opsins were expressed with diurnal rhythms similar to each other but out of phase with the rod opsin rhythm. Specifically, cone opsin expression occurs at a higher level near the onset of the dark period, when cones are not used for vision. Finally, we found that the rhythm of cone opsin expression in fish appears to be light dependent, as prolonged darkness changes normal diurnal expression patterns.