The Association Between Loneliness and Inflammation: Findings From an Older Adult Sample

Loneliness has been linked to poor mental and physical health outcomes. Past research suggests that inflammation is a potential pathway linking loneliness and health, but little is known about how loneliness assessed in daily life links with inflammation, or about linkages between loneliness and inflammation among older adults specifically. As part of a larger investigation, we examined the cross-sectional associations between loneliness and a panel of both basal and LPS-stimulated inflammatory markers. Participants were 222 socioeconomically and racially diverse older adults (aged 70&ndash;90 years; 38% Black; 13% Hispanic) systematically recruited from the Bronx, NY. Loneliness was measured in two ways, with a retrospective trait measure (the UCLA Three Item Loneliness Scale) and an aggregated momentary measure assessed via ecological momentary assessment (EMA) across 14 days. Inflammatory markers included both basal levels of C-reactive protein (CRP) and cytokines (IL-1&beta;, IL-4, IL-6, IL-8, IL-10, TNF-&alpha;) and LPS-stimulated levels of the same cytokines. Multiple regression analyses controlled for age, body-mass index, race, and depressive symptoms. Moderation by gender and race were also explored. Both higher trait loneliness and aggregated momentary measures of loneliness were associated with higher levels of CRP (&beta; = 0.16, p = 0.02; &beta; = 0.15, p = 0.03, respectively). There were no significant associations between loneliness and basal or stimulated cytokines and neither gender nor race were significant moderators. Results extend prior research linking loneliness with systemic inflammation in several ways, including by examining this connection among a sample of older adults and using a measure of aggregated momentary loneliness. &nbsp;</p

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Gender differences in the link between depressive symptoms and ex vivo inflammatory responses are associated with markers of endotoxemia

Depressive symptoms are often linked with higher inflammation and inflammatory responses, although these associations are not always consistent. In a recent study (N = 160, 25–65 years, 67% women), our group reported gender differences relevant to this association: In men higher depressive symptoms were related to heightened ex vivo inflammatory responses to lipopolysaccharide (LPS), whereas in women higher depressive symptoms were related to attenuated inflammatory responses. In the present manuscript, we investigate markers of endotoxemia – i.e., markers of the presence of endotoxin in the blood, presumably due to bacterial translocation from the gut – as factors that elicit gender-dependent immune responses that may be associated with links between depressive symptoms and inflammation. We examined ex vivo inflammatory responses in whole blood via a composite index of LPS-stimulated cytokines. The ratio of LPS-binding protein to soluble CD14 receptor (LBP:sCD14) was quantified as an index of endotoxemia that captures the relative reliance on pro-inflammatory versus non-inflammatory pathways for bacterial clearance. Levels of endotoxemia markers in blood were found to moderate gender differences in the link between depressive symptoms and stimulated inflammation (Gender × Depressive Symptoms × Endotoxemia: B = −0.039, 95%CI [-0.068, 0.009], p = 0.010). At lower LBP:sCD14 levels, depressive symptoms and stimulated inflammation were unrelated in both men and women. However, with higher levels of LBP:sCD14, men showed an increasingly positive correlation and women showed a negative correlation between depressive symptoms and stimulated inflammation. Hence, men and women exhibited similar associations between depressive symptoms and inflammatory responses at lower endotoxin marker levels, but these associations became divergent at higher levels of endotoxin markers. This information provides a novel perspective on risk factors for depression-linked alterations in inflammation, which may help to determine susceptibility to the downstream physical consequences of depressive symptomatology

Depressive Symptoms and Momentary Mood Predict Momentary Pain Among Rheumatoid Arthritis Patients.

BackgroundAlthough a relationship between mood and pain has been established cross-sectionally, little research has examined this relationship using momentary within-person data.PurposeWe examined whether baseline depressive symptoms and within-person levels of negative and positive mood predicted momentary pain among 31 individuals with rheumatoid arthritis (RA).MethodsDepressive symptomatology was measured at baseline. Mood and RA symptoms were self-reported via ecological momentary assessment five times a day for seven consecutive days. Analyses controlled for gender, age, weekend day, time of day, and experiences of stress.ResultsGreater momentary positive mood was associated with less momentary pain and fewer arthritis-related restrictions; negative mood was associated with more restrictions. Greater depressive symptomatology also predicted more pain and restrictions, an effect which was not accounted for by mood.ConclusionsResults suggest that both depression and mood are uniquely associated with momentary pain; as such, multi-component interventions may provide optimal disease management

Depressive Symptoms and Momentary Mood Predict Momentary Pain Among Rheumatoid Arthritis Patients.

BackgroundAlthough a relationship between mood and pain has been established cross-sectionally, little research has examined this relationship using momentary within-person data.PurposeWe examined whether baseline depressive symptoms and within-person levels of negative and positive mood predicted momentary pain among 31 individuals with rheumatoid arthritis (RA).MethodsDepressive symptomatology was measured at baseline. Mood and RA symptoms were self-reported via ecological momentary assessment five times a day for seven consecutive days. Analyses controlled for gender, age, weekend day, time of day, and experiences of stress.ResultsGreater momentary positive mood was associated with less momentary pain and fewer arthritis-related restrictions; negative mood was associated with more restrictions. Greater depressive symptomatology also predicted more pain and restrictions, an effect which was not accounted for by mood.ConclusionsResults suggest that both depression and mood are uniquely associated with momentary pain; as such, multi-component interventions may provide optimal disease management

The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood

Acute pain speeds skin barrier recovery in healthy men and women

OBJECTIVE: Psychological stress is known to impair skin barrier recovery, but little is known about the impact of pain on skin healing processes. Our primary goals were to examine the degree to which acute pain affects recovery from skin barrier disruption, and the potential mediating impact of cortisol and catecholamines. METHODS: Healthy non-smokers aged 18-43 (N=53, 65% women) underwent a 3-minute cold pressor pain stimulus to their foot. Tape-stripping of forearm skin occurred at two separate locations: before (site 1) and after (site 2) the pain stimulus. Transepidural water loss (TEWL) was assessed at baseline (pre-stripping), immediately post-stripping, and at 75 minutes to determine skin barrier recovery. Cortisol and catecholamine responses were obtained from multiple saliva and plasma samples, respectively. RESULTS: Contrary to expectations, greater pain was associated with faster skin barrier recovery, even after controlling for demographics, mood, anxiety, and other factors. Those who reported higher pain showed faster recovery at site 2 compared to a) individuals who experienced lower pain; and b) their own recovery at site 1. Greater increase in norepinephrine (but not in cortisol) was also associated with faster recovery at site 2, and mediated the impact of pain on recovery. DISCUSSION: Results bolster evidence that acute pain can affect immune-related processes. It is possible that acute pain may speed recovery from dermal abrasions, although pain is likely to impair recovery from more severe wounds. As pain is an important potential target for clinical intervention, further investigation of pain, stress, and healing processes is warranted