Dataset Information

Divergent gene expression responses to complicated grief and non-complicated grief.

ABSTRACT: The "widowhood effect" (i.e., morbidity/mortality in recently bereaved spouses) may be related to changes in immune function, but little is known about the impact of bereavement on gene transcription in immune cells. This study examined how Complicated Grief and Non-complicated Grief responses to bereavement differentially affect leukocyte gene expression. Genome-wide transcriptional profiling and bioinformatic analyses were completed on 63 older adults. Thirty-six of them had lost their spouse/partner on average 2years ago, and 27 were nonbereaved, married controls. Twelve of the bereaved participants met criteria for Complicated Grief. Compared to nonbereaved controls, bereavement (both Complicated Grief and Non-complicated Grief) was associated with upregulated expression of genes involved in general immunologic activation and a selective downregulation of genes involved in B lymphocyte responses. However, Complicated Grief and Non-complicated Grief differed markedly in their expression of Type I interferon-related transcripts, with Non-complicated Grief subjects showing substantial upregulation relative to nonbereaved controls and Complicated Grief subjects showing substantial downregulation. Bereavement significantly modulates immune function gene expression. The magnitude of bereavement-related distress (i.e., Complicated Grief vs. Non-complicated Grief) is linked to differential patterns of transcription factor activation and gene expression involved in innate antiviral responses. These findings provide a molecular framework for understanding the health effects of bereavement, as well as new insights into the particular gene modules that are most sensitive to the individual's psychological response to loss.

SUBMITTER: O'Connor MF

PROVIDER: S-EPMC4015725 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Divergent gene expression responses to complicated grief and non-complicated grief.

O'Connor Mary-Frances MF Schultze-Florey Christian R CR Irwin Michael R MR Arevalo Jesusa M G JMG Cole Steven W SW

Brain, behavior, and immunity 20131229

The "widowhood effect" (i.e., morbidity/mortality in recently bereaved spouses) may be related to changes in immune function, but little is known about the impact of bereavement on gene transcription in immune cells. This study examined how Complicated Grief and Non-complicated Grief responses to bereavement differentially affect leukocyte gene expression. Genome-wide transcriptional profiling and bioinformatic analyses were completed on 63 older adults. Thirty-six of them had lost their spouse/ ...[more]

PMID: 24380850

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Project description:ImportanceTo our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief.ObjectiveTo confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT.Design, setting, and participantsIncluded in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting.InterventionsAll participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions.Main outcomes and measuresComplicated grief-anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved."ResultsOf the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, -2.06 [1.00]; 95% CI, -4.02 to -0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not.Conclusions and relevanceComplicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms.Trial registrationclinicaltrials.gov Identifier: NCT01179568.

Project description:ImportanceComplicated grief (CG) is a debilitating condition, most prevalent in elderly persons. However, to our knowledge, no full-scale randomized clinical trial has studied CG in this population.ObjectiveTo determine whether complicated grief treatment (CGT) produces greater improvement in CG and depressive symptoms than grief-focused interpersonal psychotherapy (IPT).Design, setting, and participantsRandomized clinical trial enrolling 151 individuals 50 years or older (mean [SD] age, 66.1 [8.9] years) scoring at least 30 on the Inventory of Complicated Grief (ICG). Participants were recruited from the New York metropolitan area from August 20, 2008, through January 7, 2013, and randomized to receive CGT or IPT. The main outcome was assessed at 20 weeks after baseline, with interim measures collected at 8, 12, and 16 weeks after baseline.InterventionsSixteen sessions of CGT (n = 74) or IPT (n = 77) delivered approximately weekly.Main outcomes and measuresRate of treatment response, defined as a rating from an independent evaluator of much or very much improved on the Improvement subscale of the Clinical Global Impression Scale.ResultsBoth treatments produced improvement in CG symptoms. Response rate for CGT (52 individuals [70.5%]) was more than twice that for IPT (24 [32.0%]) (relative risk, 2.20 [95% CI, 1.51-3.22]; P < .001), with the number needed to treat at 2.56. Secondary analyses of CG severity and CG symptom and impairment questionnaire measures confirmed that CGT conferred a significantly greater change in illness severity (22 individuals [35.2%] in the CGT group vs 41 [64.1%] in the IPT group were still at least moderately ill [P = .001]), rate of CG symptom reduction (1.05 ICG points per week for CGT vs 0.75 points per week for IPT [t633 = 3.85; P < .001]), and the rate of improvement in CG impairment (0.63 work and Social Adjustment Scale points per week with CGT and 0.39 points per week with IPT [t503 = 2.87; P = .004]). Results were not moderated by participant age.Conclusions and relevanceComplicated grief treatment produced clinically and statistically significantly greater response rates for CG symptoms than a proven efficacious treatment for depression (IPT). Results strongly support the need for physicians and other health care providers to distinguish CG from depression. Given the growing elderly population, the high prevalence of bereavement in aging individuals, and the marked physical and psychological impact of CG, clinicians need to know how to treat CG in older adults.Trial registrationclinicaltrials.gov Identifier: NCT01244295.

Dataset Information

Divergent gene expression responses to complicated grief and non-complicated grief.

Publications

Divergent gene expression responses to complicated grief and non-complicated grief.

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