BACKGROUND: Social isolation and loneliness (known as social disconnection, collectively) lead to serious downstream health effects, including shortening of lifespan and higher risk for cardiac disease. We must better understand how isolation and loneliness lead to these negative health outcomes. Previous literature has demonstrated that social motivation and social ability are contributors to the likelihood of social isolation and loneliness. We examined the effect of the above social factors on immune gene expression in socially-connected and -isolated individuals.
METHODS: Recruitment occurred via two online advertisements, one for socially isolated individuals and another for general research participants. Participants (n = 102) were separated into groups (isolated versus connected) based on which ad they responded to, and provided data on isolation, loneliness, social motivation, and social ability. The Conserved Transcriptional Response to Adversity (CTRA) stress gene regulation program was assessed with genome-wide transcriptional profiling.
RESULTS: CTRA gene expression patterns were reversed between connected and isolated groups across several variables. Social isolation was associated with higher CTRA levels in the connected group, but lower levels in the isolated group. Social approach was associated with lower CTRA levels in the connected group, but higher in the isolated group, and the converse was true for social avoidance. CTRA levels were minimally affected by social ability measures.
CONCLUSIONS: Prior work on social isolation and loneliness has focused on loneliness and has identified many negative downstream health effects. In this study we demonstrate that objective social isolation may not be associated with the same negative downstream health effects, and in fact, social interaction may be more stressful than social isolation for some socially-isolated individuals.

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these \"silent\" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.

Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions. Participants were young adults (N = 29, aged 18 - 25 years, 62 % female, 47 % with a history of ELA). Gene expression was assessed in peripheral blood mononuclear cells collected at 8 blood draws spanning two 5-hour sessions (stress vs. no-stress) separated by a week, 4 across each session (number of observations = 221). We applied two unsupervised gene clustering methods - latent profile analysis (LPA) and weighted gene co-expression analysis (WGCNA) - to cluster genes with similar expression patterns across participants. LPA identified 11 clusters, 7 of which were significantly associated with ELA-status. WGCNA identified 5 clusters, 3 of which were significantly associated with ELA-status. LPA- and WGCNA-identified clusters were correlated, and all clusters were highly preserved across sessions and time. There was no significant effect of acute stress on cluster gene expression, but there was a significant effect of time, and significant differences by ELA-status. ELA-associated clusters related to RNA splicing/processing, inflammation, leukocyte differentiation and division, and mitochondrial activity were differentially expressed across time: ELA-exposed individuals showed decreased expression of these clusters at 90-minutes while controls showed increased expression. Our findings replicate previous work in this area and highlight additional mechanisms by which ELA may contribute to disease risk.

Early life stress (ELS) is common in the United States and worldwide, and contributes to the development of psychopathology in individuals with these experiences and their offspring. A growing body of research suggests that early life stress may contribute to adverse health partly through modulation of immune (and particularly inflammatory) responses. Therefore, increased maternal prenatal inflammation has been proposed as a mechanistic pathway by which the observed cross-generational effects of parental early life stress on child neuropsychiatric outcomes may be exerted. We examined associations between early life stress and molecular markers of inflammation (specifically pro-inflammatory gene expression and receptor-mediated transcription factor activity) and a commonly studied circulating marker of inflammation (C-Reactive Protein) in a diverse group of women in or near their third trimester of pregnancy, covarying for age, race/ethnicity, BMI, concurrent infection, concurrent perceived stress, and per capita household income. Mothers who experienced higher levels of early life stress had significantly increased pro-inflammatory (NF-κB) and decreased anti-viral (IRF) transcription factor activity. Transcripts that were up or down regulated in mothers with high ELS were preferentially derived from both CD16+ and CD16- monocytes. Early life stress was not associated with elevated CRP. Taken together, these findings provide preliminary evidence for an association between ELS and a pro-inflammatory transcriptional phenotype during pregnancy that may serve as a mechanistic pathway for cross-generational transmission of the effects of early life stress on mental and physical health.

Chronic stress threatens an individual\'s capacity to maintain psychological and physiological homeostasis, but the molecular processes underlying the biological embedding of these experiences are not well understood. This is particularly true for marginalized groups, presenting a fundamental challenge to decreasing racial, economic, and gender-based health disparities. Physical and social environments influence genome function, including the transcriptional activity of core stress responsive genes. We studied the relationship between social experiences that are associated with systemic inequality (e.g., racial segregation, poverty, and neighborhood violence) and blood cell (leukocytes) gene expression, focusing on the activation of transcription factors (TF) critical to stress response pathways. The study used data from 68 women collected from a convenience sample in 2013 from the Southside of Chicago. Comparing single, low-income Black mothers living in neighborhoods with high levels of violence (self-reported and assessed using administrative police records) to those with low levels of violence we found no significant differences in expression of 51 genes associated with the Conserved Transcriptional Response to Adversity (CTRA). Using TELiS analysis of promoter TF-binding motif prevalence we found that mothers who self-reported higher levels of neighborhood stress showed greater expression of genes regulated by the glucocorticoid receptor (GR). These findings may reflect increased cortisol output from the hypothalamic-pituitary-adrenal (HPA) axis, or increased GR transcriptional sensitivity. Transcript origin analyses identified monocytes and dendritic cells as the primary cellular sources of gene transcripts up-regulated in association with neighborhood stress. The prominence of GR-related transcripts and the absence of sympathetic nervous system-related CTRA transcripts suggest that a subjective perception of elevated chronic neighborhood stress may be associated with an HPA-related defeat-withdrawal phenotype rather than a fight-or-flight phenotype. The defeat-withdrawal phenotype has been previously observed in animal models of severe, overwhelming threat. These results demonstrate the importance of studying biological embedding in diverse environments and communities, specifically marginalized populations such as low-income Black women.

Aaron Beck\'s insight-that beliefs about one\'s self, future, and environment shape behavior-had major implications for health psychology research and practice. Yet, beliefs about one\'s environment have remained relatively understudied. A recent comprehensive empirically-driven effort has led to the identification of 26 primal world beliefs, or primals, (e.g., the world is: harmless vs. threatening, stable vs. fragile, just vs. unjust, meaningful vs. meaningless, improvable vs. too hard to improve, beautiful vs. ugly). Primals have been theorized to influence many outcomes of interest to different psychological subdisciplines, and a psychometrically rigorous effort has developed a Primals Inventory to measure them. In this brief report, we aim to introduce primals\' potential implications for health psychology research and practice. After summarizing primals\' theorized general function, we illustrate their connection to health processes and outcomes via five illustrative hypotheses. These hypotheses concern how primals might influence (a) the cardiotoxic stress axis; (b) conserved transcriptional response to adversity gene expression patterns; (c) health behaviors; (d) treatment effectiveness; and (e) risk of developing chronic diseases. Further research on primals in relation to health processes and outcomes might lead to new avenues of scientific inquiry and innovative methods of improving the trajectory of our society\'s health and well-being.

There is considerable evidence for the effectiveness of mind-body interventions (MBIs) in improving mental and physical health, but the molecular mechanisms of these benefits remain poorly understood. One hypothesis is that MBIs reverse expression of genes involved in inflammatory reactions that are induced by stress. This systematic review was conducted to examine changes in gene expression that occur after MBIs and to explore how these molecular changes are related to health. We searched PubMed throughout September 2016 to look for studies that have used gene expression analysis in MBIs (i.e., mindfulness, yoga, Tai Chi, Qigong, relaxation response, and breath regulation). Due to the limited quantity of studies, we included both clinical and non-clinical samples with any type of research design. Eighteen relevant studies were retrieved and analyzed. Overall, the studies indicate that these practices are associated with a downregulation of nuclear factor kappa B pathway; this is the opposite of the effects of chronic stress on gene expression and suggests that MBI practices may lead to a reduced risk of inflammation-related diseases. However, it is unclear how the effects of MBIs compare to other healthy interventions such as exercise or nutrition due to the small number of available studies. More research is required to be able to understand the effects of MBIs at the molecular level.

Cognitive behavioral stress management (CBSM) is an empirically-validated group-based psychosocial intervention. CBSM is related to decreased self-reported indicators of psychological adversity during breast cancer treatment and greater disease-free survival (DFS) vs. a control condition. This study examined relationships between CBSM, DFS, and a potential biobehavioral pathway linking these variables in breast cancer patients through a gene expression composite representing the leukocyte conserved transcriptional response to adversity (CTRA).
Women with stage 0-IIIb breast cancer completed questionnaires and provided blood samples post-surgery. Participants were randomized to 10-week group-based CBSM or a psychoeducation control group and followed at 6 months, 12 months, and median 11 years. In total, 51 participants provided blood data for longitudinal analyses (CBSM n=28; Control n=23). Mixed model analyses examined CBSM effects on 6-12 month changes in CTRA expression (53 indicator genes representing pro-inflammatory, anti-viral and antibody production signaling). Cox regression models assessed the relationship between 6 and 12 month changes in CTRA expression and 11-year DFS.
Patients randomized to CBSM showed attenuated 6-12 month change in CTRA gene expression, whereas patients randomized to control showed increased CTRA expression (p=0.014). Average DFS was 5.92 years (SD=3.90). Greater 6-12 month CTRA increases predicted shorter 11-year DFS controlling for covariates (p=0.007).
CBSM attenuated CTRA gene expression during the initial year of breast cancer treatment. In turn, greater increases in CTRA gene expression predicted shorter long-term DFS. These findings identify a biobehavioral oncology pathway to examine in future work.