Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder.

Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure's antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: χ2(3, N=108) = 47.33, p < 0.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (F(1, 102.3) = 6.74, p = 0.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.

Objectively Measured Social Integration Is Associated With an Immune Risk Phenotype Following Marital Separation.

Background: Close relationships play an integral role in human development, and robust evidence links marital separation and divorce to poor health outcomes. Social integration may play a key role in this association. In many ways, the study of marital separation and divorce provides an ideal model system for a more complete understanding of the association between life stress and physical health. Purpose: The current study investigated associations among objectively measured social integration, psychological distress, and biomarkers of immune health in recently separated adults (N = 49). Methods: We collected four measures of immune functioning-interleukin-6, C-reactive protein, and antibody titers to latent cytomegalovirus and Epstein-Barr virus-that were combined to yield a viral-Immune Risk Profile. To assess how variability in social integration is associated with immunological correlates following the end of a marriage, we incorporated observational ecological momentary assessment data using a novel methodology (the Electronically Activated Recorder). Results: We found that objectively measured social behaviors are associated with concurrent viral-Immune Risk Profile scores over and above the effects of psychological distress and that psychological distress may be linked to biomarkers of immune health through social integration. Conclusions: This research expands current knowledge of biomarkers of immune health after divorce and separation and includes a new methodology for objective measures of social engagement.

Natural language indicators of differential gene regulation in the human immune system.

Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social-environmental variables more closely than they do self-reported internal affective states such as stress, depression, or anxiety. This study examined the possibility that variations in patterns of natural language use might provide more sensitive indicators of the automatic threat-detection and -response systems that proximally regulate autonomic induction of the CTRA. In 22,627 audio samples of natural speech sampled from the daily interactions of 143 healthy adults, both total language output and patterns of function-word use covaried with CTRA gene expression. These language features predicted CTRA gene expression substantially better than did conventional self-report measures of stress, depression, and anxiety and did so independently of demographic and behavioral factors (age, sex, race, smoking, body mass index) and leukocyte subset distributions. This predictive relationship held when language and gene expression were sampled more than a week apart, suggesting that associations reflect stable individual differences or chronic life circumstances. Given the observed relationship between personal expression and gene expression, patterns of natural language use may provide a useful behavioral indicator of nonconsciously evaluated well-being (implicit safety vs. threat) that is distinct from conscious affective experience and more closely tracks the neurobiological processes involved in peripheral gene regulation.

Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.

IMPORTANCE: Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention. OBJECTIVE: To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment. DESIGN, SETTING, AND PARTICIPANTS: A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater. INTERVENTIONS: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. MAIN OUTCOMES AND MEASURES: Between-group differences in postintervention Hamilton Depression Rating Scale scores. RESULTS: The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild. CONCLUSIONS AND RELEVANCE: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01625546.

Cancer conversations in context: naturalistic observation of couples coping with breast cancer.

This study explored the feasibility and potentials of a naturalistic observation approach to studying dyadic coping in everyday life. Specifically, it examined the natural context and content of the spontaneous cancer conversations of couples coping with cancer, and how they relate to patients' and spouses' psychological adjustment. Women with breast cancer (N = 56) and their spouses wore the electronically activated recorder (EAR), an unobtrusive observation method that periodically records snippets of ambient sounds, over one weekend to observe the couples' cancer conversations in their natural context. Both patients and spouses completed self-reported measures of psychological adjustment at baseline and at a 2-month follow-up. Cancer was a topic of approximately 5% of couples' conversations. Cancer conversations occurred more often within the couple than with friends and family, and they were more often informational than emotional or supportive. Consistent with research on the social cognitive processing model (Lepore & Revenson, 2007), spouses' engagement in emotional disclosure and informational conversation with patients predicted better patient adjustment. This first naturalistic observation study of dyadic coping revealed that the EAR method can be implemented with high compliance and relatively low obtrusiveness within the sensitive context of couples coping with cancer, and having a spouse who discussed cancer in an emotional or informational way predicted better patient adjustment. As a complement to in-lab and other momentary assessment methods, a naturalistic observation approach with a method such as the EAR can contribute to a more comprehensive understanding of the role that communication processes play in coping with cancer.

Asymmetric partner pronoun use and demand-withdraw interaction in couples coping with health problems.

Recent research links first-person plural pronoun use (we-talk) by individual romantic partners to adaptive relationship functioning and individual health outcomes. To examine a possible boundary condition of adaptive we-talk in couples coping with health problems, we correlated asymmetric couple-level we/I-ratios (more we-talk relative to I-talk by the spouse than the patient) with a concurrent pattern of directional demand-withdraw (D-W) interaction in which the spouse demands change while the patient withdraws. Couples in which a partner who abused alcohol (n = 65), smoked cigarettes despite having heart or lung disease (n = 24), or had congestive heart failure (n = 58) discussed a health-related disagreement during a video-recorded interaction task. Transcripts of these conversations provided measures of pronoun use for each partner, and trained observers coded D-W patterns from the recordings. As expected, partner asymmetry in we/I-ratio scores predicted directional demand-withdraw, such that spouses who used more we-talk (relative to I-talk) than patients tended to assume the demand role in concurrent D-W interaction. Asymmetric I-talk rather than we-talk accounted for this association, and asymmetric you-talk contributed independently as well. In contrast to previous studies of we-talk by individual partners, the present results identify dyad-level pronoun patterns that clearly do not mark beneficent processes: asymmetric partner we/I-ratios and you-talk reflect problematic demand-withdraw interaction.

Linguistic indicators of patient, couple, and family adjustment following breast cancer.

BACKGROUND: This study examined how language reflective of emotional and social processes during a cancer-related discussion relates to patient, couple, and family adjustment after breast cancer. It investigated whether emotional expression or relational focus, manifested in language use, indicates healthy family coping following breast cancer. METHODS: Family members each completed measures of adjustment (Family Environment Scale, Dyadic Adjustment Scale, and patient Profile of Mood States) and engaged in a 15-min family discussion about how they have coped with breast cancer. Transcripts from the discussion were submitted to a text-analysis software program to obtain frequency of positive and negative emotion words, and personal pronouns spoken by each family member. The relationship between self-reports of adjustment and frequency of language use during the family discussion was analyzed with regression models. RESULTS: Partners' positive emotion words were indicative of better family adjustment, patients' negative emotion words indicated greater family conflict, and sons' and daughters' anger words indicated poorer adjustment, whereas their anxiety words indicated better family adjustment. Partner we-talk was related to better dyadic adjustment, and couples' 'you' was somewhat related to worse adjustment at all levels. CONCLUSIONS: Important information about how a family copes with breast cancer can be obtained by attending to families' emotional and relational language. This study suggests that clinicians and members of families' support networks can gauge how well a family has adapted after the breast cancer experience by attending to the type of words that each family member uses to describe how they coped with breast cancer.

We-talk, communal coping, and cessation success in a couple-focused intervention for health-compromised smokers.

We investigated first-person plural pronoun use (we-talk) by health-compromised smokers and their spouses as a possible implicit marker of adaptive, problem-resolving communal processes. Twenty couples in which one or both partners used tobacco despite one of them having a heart or lung problem participated in up to 10 sessions of a smoking cessation intervention designed to promote communal coping, where partners define smoking as "our" problem, rather than "your" problem or "my" problem, and take collaborative action to solve it. We used the Linguistic Inquiry Word Count automatic text analysis program to tabulate first-person pronoun use by both partners from transcripts of a pretreatment marital interaction task and later intervention sessions. Results indicated that pretreatment we-talk by the patient's spouse predicted whether the patient remained abstinent 12 months after quitting, and residualized change in we-talk by both partners during the course of intervention (controlling for baseline levels) predicted cessation outcomes as well. These findings add to evidence regarding the prognostic significance of partner we-talk for patient health and provide preliminary documentation of communal coping as a possible mechanism of change in couple-focused intervention.

Naturalistically observed swearing, emotional support, and depressive symptoms in women coping with illness.

OBJECTIVE: The goal of this study was to explore the intra- and interpersonal consequences of swearing. Specifically, it investigated what implications swearing has for coping with and adjustment to illness. METHODS: The present project combined data from two pilot studies of 13 women with rheumatoid arthritis and 21 women with breast cancer. Participants wore the Electronically Activated Recorder, an unobtrusive observation sampling method that periodically records snippets of ambient sounds, on weekends to track spontaneous swearing in their daily interactions, and completed self-reported measures of depressive symptoms and emotional support. RESULTS: Naturalistically observed swearing in the presence of others, but not alone, was related to decreases in reported emotional support and increases in depressive symptoms over the study period. Further, decreases in emotional support mediated the effect of swearing on disease-severity adjusted changes in depressive symptoms. CONCLUSION: These exploratory results are consistent with the notion that swearing can sometimes repel emotional support at the expense of psychological adjustment. This is one of the first studies to examine the role of swearing, a ubiquitous but understudied psychological phenomenon, in a medical context.