A tale of two marital stressors: Comparing proinflammatory responses to partner distress and marital conflict.

Marital quality shares ties to inflammatory conditions like cardiovascular disease and diabetes. For decades, research has focused on marital conflict as a primary mechanism given its potential to trigger inflammatory responses. However, longitudinal evidence suggests that marital conflict declines over time, and little attention has been paid to the inflammatory aftermath of other types of marital exchanges. A spouse's emotional distress is an important but overlooked marital context, as partners are exposed to each other's upsetting emotions throughout adulthood. To directly compare reactivity in proinflammatory gene expression to these two marital stressors and to examine differences by age and marital satisfaction, 203 community adults ages 25-90 (N = 102 couples) provided blood samples and rated their negative mood before and after they 1) watched their partner relive an upsetting personal memory and, in a separate visit 1-2 weeks later, 2) discussed a conflictual topic in their relationship. Controlling for age, sex, race/ethnicity, BMI, alcohol use, smoking, and comorbidities, increases in proinflammatory gene expression were significantly larger after the partner's upsetting disclosure than after marital conflict (B = 0.073, SE = 0.031, p = .018). This pattern paralleled emotional reactivity to the tasks, wherein negative mood rose more in response to the partner's disclosure than to marital conflict (B = 4.305, SE = 1.468, p = .004). In sum, proinflammatory and mood reactivity to spousal distress exceeded reactivity to marital conflict, a well-established marital stressor. Findings reveal spousal distress as a novel mechanism that may link marriage to inflammation-related diseases, and even pose risks for both happy and unhappy couples across adulthood.

Psychoneuroimmunology in multiple myeloma and autologous hematopoietic stem cell transplant: Opportunities for research among patients and caregivers.

Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients. An extensive psychoneuroimmunology (PNI) literature links distress with health via immune and neuroendocrine dysregulation as well as biological aging. However, data on PNI in the context of multiple myeloma - in patients or caregivers - are remarkably limited. Distress in MM patients has been associated with poorer outcomes including higher inflammation, greater one year post-HSCT hospital readmissions, and worse overall survival. Further, anxiety and depression are linked to biological aging and may contribute to the poor long-term health of both patients and caregivers. Because MM generally affects older adults, individual differences in biological aging may represent an important modifier of MM biology and HSCT treatment outcomes. There are a number of clinical scenarios in which biologically younger people could be prescribed more intensive therapies, with potential for greater benefit, by using a personalized cancer therapy approach based on the quantification of physiologic reserve. Further, despite considerable psychological demands, the effects of distress on health among MM caregivers is largely unexamined. Within this context, the current critical review highlights gaps in knowledge at the intersection of HSCT, inflammation, and biological aging in the context of MM. Research in this area hold promise for opportunities for novel and impactful psychoneuroimmunology (PNI) research to enhance health outcomes, quality of life, and longevity among both MM patients and their caregivers.

Geochemical factors impacting nitrifying communities in sandy sediments.

Sandy sediment beaches covering 70% of non-ice-covered coastlines are important ecosystems for nutrient cycling along the land-ocean continuum. Subterranean estuaries (STEs), where groundwater and seawater meet, are hotspots for biogeochemical cycling within sandy beaches. The STE microbial community facilitates biogeochemical reactions, determining the fate of nutrients, including nitrogen (N), supplied by groundwater. Nitrification influences the fate of N, oxidising reduced dissolved inorganic nitrogen (DIN), making it available for N removal. We used metabarcoding of 16S rRNA genes and quantitative PCR (qPCR) of ammonia monooxygenase (amoA) genes to characterise spatial and temporal variation in STE microbial community structure and nitrifying organisms. We examined nitrifier diversity, distribution and abundance to determine how geochemical measurements influenced their distribution in STEs. Sediment microbial communities varied with depth (p-value = 0.001) and followed geochemical gradients in dissolved oxygen (DO), salinity, pH, dissolved inorganic carbon and DIN. Genetic potential for nitrification in the STE was evidenced by qPCR quantification of amoA genes. Ammonia oxidiser abundance was best explained by DIN, DO and pH. Our results suggest that geochemical gradients are tightly linked to STE community composition and nitrifier abundance, which are important to determine the fate and transport of groundwater-derived nutrients to coastal waters.

Modeling the mechanisms of conifer mortality under seawater exposure.

Relative sea level rise (SLR) increasingly impacts coastal ecosystems through the formation of ghost forests. To predict the future of coastal ecosystems under SLR and changing climate, it is important to understand the physiological mechanisms underlying coastal tree mortality and to integrate this knowledge into dynamic vegetation models. We incorporate the physiological effect of salinity and hypoxia in a dynamic vegetation model in the Earth system land model, and used the model to investigate the mechanisms of mortality of conifer forests on the west and east coast sites of USA, where trees experience different form of sea water exposure. Simulations suggest similar physiological mechanisms can result in different mortality patterns. At the east coast site that experienced severe increases in seawater exposure, trees loose photosynthetic capacity and roots rapidly, and both storage carbon and hydraulic conductance decrease significantly within a year. Over time, further consumption of storage carbon that leads to carbon starvation dominates mortality. At the west coast site that gradually exposed to seawater through SLR, hydraulic failure dominates mortality because root loss impacts on conductance are greater than the degree of storage carbon depletion. Measurements and modeling focused on understanding the physiological mechanisms of mortality is critical to reducing predictive uncertainty.

Older Adults' Social Profiles and Links to Functional and Biological Aging in the United States and Mexico.

OBJECTIVE: Social stress-loneliness, isolation, and low relationship quality-increase risks for aging-related diseases. However, the ways in which they intersect to undermine healthy aging remain poorly understood. We utilized latent class analysis to identify groups of older adults based on their social stress in both the United States and Mexico. Thereafter, we examined their cross-sectional associations with markers of functional and biological aging. METHOD: Participants in the Health and Retirement Study (HRS, N = 8,316) and Mexican Health and Aging Study (MHAS, N = 15,001) reported their loneliness, isolation (i.e., living alone), and relationship quality with spouse, children, and friends. Outcomes included C-reactive protein (CRP), functional limitations, self-rated health, comorbidities, gait speed, and grip strength. Models controlled for demographics, health behaviors, and body mass index (BMI). RESULTS: In both countries, five classes emerged, a Supported group and four with elevated social stress: (1) Strained, (2) Isolated, (3) Spousal Ambivalence, and (4) Unhappily Married. Compared to the others, Strained participants in both samples had greater functional limitations, poorer self-rated health, and more comorbidities, as well as slower gait in HRS and weaker grip in MHAS. Generally, Supported participants fared better than the other groups. In HRS, CRP levels differed between the Strained group and others, but these associations were explained by health behaviors and BMI. CONCLUSIONS: Older adults in both countries with strained relationships fared worst in their aging-related outcomes, revealing new insights about the links between toxic social stress and unhealthy aging.

Depression, Inflammation, and the Moderating Role of Metformin: Results from the Midlife in the United States (MIDUS) Study and Sacramento Area Latino Study on Aging (SALSA).

OBJECTIVE: Depression can promote inflammation and accelerate aging. Metformin, a widely prescribed antidiabetic, has shown promising preclinical evidence of aging-related health benefits, including decreased inflammation. The current study examined whether metformin usage buffers the association between depressive symptoms and inflammatory markers in two large samples of middle-aged and older, primarily white adults, and older Latino adults. METHODS: Data from the Midlife in the United States Study (MIDUS; N = 1255) and the Sacramento Area Latino Study on Aging (SALSA; N = 1786) included information on medication use, depressive symptoms, and inflammatory markers, namely IL-6, TNF-α, and CRP. These data were merged into a harmonized sample, and the sample group variable was included in a three-way interaction for analysis. RESULTS: Specifically, in the MIDUS sample, metformin buffered the association between depressive symptoms and CRP (b = -0.029, SE = 0.013, p = .007) and IL-6 (b = 0.21, SE = 0.010, p = .046), while no significant association was found with TNF-α. Metformin non-users displayed higher depressive symptoms associated with elevated CRP (b = 0.01, SE = 0.003, p < .001) and IL-6 (b = 0.011, SE = 0.003, p < .001), whereas this association was not present among metformin users (ps > .068). Conversely, in the SALSA sample, metformin use did not show a significant protective link. CONCLUSION: Results from mostly white, highly educated adults supported a mitigating role of metformin in ties between depression, a well-known behavioral risk factor, and inflammation, a key source of biological aging. However, the benefits did not extend to a large sample of older Mexican Americans. The findings reveal a hidden potential benefit of this therapeutic agent and raise important questions around its health equity.Trial Registration: The study was pre-registered on OSF (https://osf.io/c92vw/).

"We've Got This": Middle-Aged and Older Couples' Satisfying Relationships and We-Talk Promote Better Physiological, Relational, and Emotional Responses to Conflict.

OBJECTIVE: Conflict poses multiple relational and health risks. Dyadic stress theories suggest satisfaction and communication alter cardiovascular and autonomic function, key pathways from troubled relationships to poor health. However, "we-talk," a positive communication pattern, can strengthen relationships and promote health. We examined how each spouse's satisfaction and we-talk were related to conflict's physiological, relational, and emotional toll. METHODS: Married couples ( n = 107 couples, 214 individuals, ages 40-87 years) who were mostly White, highly educated, and higher-income Americans in different-gender relationships engaged in 20-minute conflict discussions while wearing monitors to assess heart rate variability (HRV). Spouses rated their closeness immediately after conflict and their conflict rumination 2 hours later. Conflict transcriptions measured we-talk, or the proportion of first-person plural pronouns (we, us, our). RESULTS: Satisfied spouses or those in mutually satisfying relationships had higher HRV during conflict ( b = 0.0001, p = .049), felt closer immediately after conflict ( b = 0.07, p < .001), and ruminated less about the conflict 2 hours later ( b = -0.26, p = .026). Spouses' HRV was highest ( b = 0.0002, p = .002) and rumination was lowest ( b = -0.49, p = .019) when they or their partners were satisfied and used we-talk more often. Women's HRV ( b = 0.0001, p = .035) and rumination ( b = -0.01, p = .02) benefited when both spouses were satisfied, as did closeness when women were satisfied ( b = 0.10, p < .001). Men's closeness benefited when they ( b = 0.04, p = .003) or their wives ( b = 0.04, p = .002) were satisfied. CONCLUSIONS: The combination of mutually satisfying relationships and we-talk was associated with better relational and health outcomes after conflict. These findings are important for middle-aged and older couples whose relationships are central to their health.

Intimate Partner Violence and Inflammaging: Conflict Tactics Predict Inflammation Among Middle-Aged and Older Adults.

OBJECTIVE: In long-term relationships, conflict is inevitable, but physical and psychological aggression is not. Intimate partner violence (IPV) is a known risk factor for age-related disease onset, and inflammation likely links the two. This study explores relationships between frequency of constructive (i.e., negotiation) and destructive (i.e., aggression) conflict tactics with inflammation in both younger and older adulthood. Based on the theory of inflammaging, the study investigates whether these associations were stronger in mid-to-late adulthood. METHODS: At one visit, 214 participants in long-term romantic relationships had their blood drawn to assess six inflammatory markers (interleukin-6, IL-6; tumor necrosis factor-alpha, TNF-α; c-reactive protein, CRP; serum amyloid A, SAA; soluble intercellular adhesion molecule, sICAM; soluble vascular cell adhesion molecule, sVCAM) and reported frequency of destructive and constructive conflict tactics with their partner in the past year on the Revised Conflict Tactics Scale short form. RESULTS: Age interacted with number of destructive conflicts per year to predict serum IL-6 (F(1, 200) = 5.3, p = .022), TNF-α (F(1, 180) = 4.2, p = .043), sICAM (F(1, 193) = 7.0, p = .008), and marginally SAA (F(1, 199) = 3.7, p = .055), such that middle-aged and older adults who reported more destructive tactics had higher inflammation. Also, the relationship between constructive conflict frequency and TNF-α also depended on age (F(1, 177) = 4.9, p = .029), in that older adults who reported a greater number of constructive tactics had lower TNF-α. CONCLUSION: Couples' conflict tactics may influence levels of inflammation, and, therefore, aging rate, in mid-to-late life. Middle-aged and older adults may disproportionately benefit from a healthy partnership and suffer from an unhealthy partnership.

The Days Add Up: Daily Marital Discord and Depressive Reactivity Linked to Past-Month Depressed Mood and Marital Risk across 10 Years.

Marital discord fuels depression, according to decades of research. Most prior studies in this area have focused on macro-longitudinal change in depression over the course of years, and on global ratings of marital satisfaction. Less work has examined fluctuations in depressed mood and marital discord in daily life, and none has investigated associations of short-term patterns with longer-term depressed mood and marital outcomes. Using data from participants in the Midlife in the U.S. (MIDUS) project, the current study examined daily associations between marital discord and depressed mood, as well as their links to concurrent and prospective patterns of past-month depressed mood and marital risk. Results showed that, on average, depressed mood rose on days when individuals had an argument or tension with their spouse (i.e., marital discord). More frequent daily marital discord was also associated with greater past-month depressed mood and marital risk, above and beyond prior levels. Those with larger depressive mood responses to discord in daily life (i.e., greater reactivity) exhibited higher concurrent past-month depressed mood and greater 10-year increases in depressed mood. As the first study to link daily marital patterns to concurrent and prospective changes in depressed mood and marital outcomes, this investigation uncovered two novel processes-daily marital discord and depressive reactivity-as important for understanding long-term patterns of marital risk and depression.

The Implications of Being "In it Together": Relationship Satisfaction and Joint Health Behaviors Predict Better Health and Stronger Concordance Between Partners.

BACKGROUND: Extensive evidence shows that satisfying marriages boost physical health and longevity. A separate literature reveals strong concordance in couples' health, but the relationship processes that contribute to health concordance remain poorly understood. PURPOSE: The current study examined whether relationship satisfaction and joint health behaviors-the extent to which couples eat, sleep, and exercise together-are associated simultaneously with better health and greater health similarity between partners. METHODS: Heterogeneous variance multilevel models were applied to data from 234 married couples (Mage = 46, Range = 20-84) reporting on their relationship satisfaction, joint health behaviors, and four health indicators-health satisfaction, depressive symptoms, comorbidities, and medication use. RESULTS: More satisfied couples engaged in more joint health behaviors than less satisfied counterparts. When joint health behaviors and relationship satisfaction were examined as separate fixed effects, both predicted greater health satisfaction and fewer depressive symptoms. More joint health behaviors were also associated with less medication use. When both were modeled together, only relationship satisfaction predicted depressive symptoms. By contrast, in random effects, joint health behaviors predicted greater similarity in health satisfaction, depressive symptoms, and comorbidities. Relationship satisfaction only predicted more similar depressive symptoms. CONCLUSIONS: Although more satisfied couples engaged in more joint health behaviors. relationship satisfaction and joint health behaviors uniquely predicted couples' health quality and concordance, suggesting that distinct mechanisms may drive better health and stronger health resemblance.

Interpersonal behavior in couple therapy: Concurrent and prospective associations with depressive symptoms and relationship distress.

Objective: This study investigated associations between couples' interpersonal behavior, depressive symptoms, and relationship distress over the course of couple psychotherapy. Method: After every other session of Integrative Systemic Therapy (M = 13 sessions), N = 100 individuals within 50 couples rated their in-session affiliation and autonomy behavior using the circumplex-based Structural Analysis of Social Behavior Intrex. Concurrent and prospective associations of interpersonal behavior with depressive symptoms and relationship distress were evaluated via multivariate multilevel modeling using the Actor-Partner Interdependence Model. Results: An individual's hostility, as well as the partner's hostility, positively predicted an individual's concurrent depressive symptoms and relationship distress, as well as his or her relationship distress at the following session. Partner hostility during one session predicted an individual's subsequent depressive symptoms. During sessions in which individuals controlled the partner, and separated themselves from the partner, they reported more concurrent depressive symptoms and relationship distress, and more subsequent relationship distress. When partners separated themselves, individuals reported more concurrent depressive symptoms and relationship distress, and more subsequent relationship distress. Conclusions: Results underscore the importance of couples' in-session affiliation and autonomy behavior in the treatment of depressive symptoms and relationship distress within couple therapy.

Marriage and Gut (Microbiome) Feelings: Tracing Novel Dyadic Pathways to Accelerated Aging.

Within a couple, partners influence each other's mental and physical health. This review focuses on how couples' relationships, the partners' individual and joint vulnerabilities, and their health behaviors influence health through changes in the gut microbiota, metabolism, and immune function. Couples' shared stressors and emotions and their intertwined lifestyles and routines serve to promote common disease risks in part through parallel changes in their gut microbiotas. Marital discord, stress, and depression have strong bidirectional links, fueling one another. Chronic marital stress and depression can elevate the risk for obesity, metabolic syndrome, and cardiovascular disease by altering resting energy expenditure, insulin production, and triglyceride responses after unhealthy meals. During stressful times, health behaviors typically suffer-and sleep disturbances, poor diets, and sedentary behavior all influence these metabolic pathways while also promoting gut dysbiosis. Dysbiosis increases intestinal permeability (gut leakiness), providing a mechanistic pathway from marital distress and depression to heightened inflammation and accelerated aging. Age-related changes in the gut microbiota's composition and gut leakiness foster immunosenescence, as well as the progression of inflamm-aging; these age-related risks may be altered by stress and depression, diet, sleep, exercise habits, and developmental shifts in emotion regulation strategies. Consideration of the strong mutual influences that partners have on each other's mood and health behaviors, as well as the biological pathways that underlie these influences, provides a new way to view marriage's health implications.

A proinflammatory diet is associated with inflammatory gene expression among healthy, non-obese adults: Can social ties protect against the risks?

The Western diet, characterized by high intake of saturated fat, sugar, and salt, is associated with elevated inflammation and chronic disease risk. Few studies have investigated molecular mechanisms linking diet and inflammation; however, a small number of randomized controlled trials suggest that consuming an anti-inflammatory diet (i.e., a primarily plant-based diet rich in monounsaturated fat and lean protein) decreases proinflammatory gene expression. The current study investigated the association between everyday diet and proinflammatory gene expression, as well as the extent to which central adiposity and social involvement modulate risk. Participants were healthy middle-aged and older adults (N = 105) who completed a food frequency questionnaire and reported how many close social roles they have. Anthropometric measurements and blood samples also were collected; gene expression data were analyzed from LPS-stimulated peripheral blood mononuclear cells for interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. The inflammatory potential of each participant's diet was calculated using the Dietary Inflammatory Index (DII®). Participants with higher DII® scores, indicating a more proinflammatory diet, had greater IL-6 (b = -0.02, SE = 0.008, p = .01), IL-1ß (b = -0.01, SE = 0.006, p = .03), and TNF-α (b = -0.01, SE = 0.005, p = .04) gene expression if they had a smaller sagittal abdominal diameter (SAD); effects were not seen among those with higher SADs. Social involvement served a protective role, such that participants with smaller SADs had greater IL-6 (b = 0.01, SE = 0.004, p = .049) and IL-1ß (b = 0.01, SE = 0.003, p = .045) gene expression only if they had less social involvement; there was no effect of diet on gene expression among those who reported greater social participation. Results are the first to demonstrate a link between self-reported diet and proinflammatory gene expression. Importantly, the effect of diet on gene expression depended upon both body fat composition and social participation, both of which have previously been linked directly with proinflammatory gene expression and inflammation.

Loneliness and Telomere Length: Immune and Parasympathetic Function in Associations With Accelerated Aging.

BACKGROUND: Lonely people's heightened risks for chronic health conditions and early mortality may emerge in part through cellular aging. Lonelier people have more severe sympathetic responses to acute stress, increasing their risk for herpesvirus reactivation, a possible path to shorter telomeres. Parasympathetic function may modulate this risk. PURPOSE: The current study aimed to examine the associations among loneliness, herpesvirus reactivation, and telomere length, with parasympathetic activity as a moderator, in healthy middle-aged and older adults. METHODS: A sample of 113 healthy men and women of ages 40-85 provided blood samples that were assayed for telomere length, as well as the latent herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV). They also provided heart rate variability (HRV), a measure of parasympathetic activity, and reported on their feelings of loneliness. RESULTS: Lonelier people with lower HRV (i.e., lower parasympathetic activity) had greater CMV reactivation and shorter telomeres compared with their less lonely counterparts, above and beyond demographics, health behaviors, resting heart rate, and social network size. However, loneliness was not associated with viral reactivation or telomere length among those with higher HRV. In turn, greater CMV and EBV reactivation was associated with shorter telomeres. CONCLUSIONS: Taken together, these data implicate parasympathetic function in novel links between loneliness and accelerated cellular aging.

Physical Activity After Breast Cancer Surgery: Does Depression Make Exercise Feel More Effortful than It Actually Is?

BACKGROUND: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients' depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. METHODS: Participants were 106 breast cancer patients, stages I-IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. RESULTS: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p = .010) but had similar heart rates (p = .224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps > .224) and heart rate (ps > .200) during exercise. CONCLUSIONS: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients' likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.

Daily Spousal Responsiveness Predicts Longer-Term Trajectories of Patients' Physical Function.

Everyday interpersonal experiences may underlie the well-established link between close relationships and physical health, but multiple-timescale designs necessary for strong conclusions about temporal sequence are rarely used. The current study of 145 patients with knee osteoarthritis and their spouses focused on a novel pattern in everyday interactions, daily spousal responsiveness-the degree to which spouses' responses are calibrated to changes in patients' everyday verbal expression of pain. Using couple-level slopes, multilevel latent-variable growth models tested associations between three types of daily spousal responsiveness (empathic, solicitous, and punishing responsiveness), as measured during a 3-week experience-sampling study, and change in patients' physical function across 18 months. As predicted, patients whose spouses were more empathically responsive to their pain expression showed better physical function over time compared with those whose spouses were less empathically responsive. This study points to daily responsiveness, a theoretically rooted operationalization of spousal sensitivity, as important for long-term changes in patients' objective physical function.

Lovesick: How Couples' Relationships Influence Health.

This review highlights recent advances in research addressing intimate partner relationships and health. Consideration of the strong mutual influences that the members of a couple have on each other's mental and physical health trajectories provides a new way to view the health implications of couples' convergence or interdependence; marital closeness can have a clear downside when one partner has mental or physical health problems. Couples' interconnectedness can also be leveraged to promote better treatment outcomes. Major themes include the pivotal role of depression and the importance of gender differences in the pathways from the marital relationship to physiological functioning and health. The health risks and benefits of support are weighed. Additionally, two prominent emerging paths from marital distress to poor health are emphasized: sleep problems and metabolic alterations that promote obesity and its comorbidities.

Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging.

A meta-analysis published in this issue of Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed: DNA methylation and cellular senescence based on p16. These innovative approaches could be used to confirm and extend our understanding of psychiatric patients' increased health and mortality risks.

Gut Microbiota Richness and Diversity Track With T Cell Aging in Healthy Adults.

BACKGROUND: This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan. METHODS: Peripheral blood was obtained from 96 study participants (N = 96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation. T cell aging mRNA markers were combined into an aging index, and the Horvath epigenetic clock algorithm was used to calculate epigenetic age based on DNA methylation status of over 500 loci. Participants also collected a stool sample from which the V4 region of the 16S rRNA gene was sequenced to derive the Shannon and Simpson diversity indices, and the total count of observed operational taxonomic units (richness). Models controlled for BMI, comorbidities, sex, dietary quality, smoking status, physical activity, and sleep quality. RESULTS: Lower microbiota richness was associated with higher T cell age based on mRNA markers, but when probing the region of significance, this relationship was only significant among adults 45 years and older (p = .03). Lower Shannon diversity (p = .05) and richness (p = .07) marginally correlated with higher epigenetic age (ie, greater T cell DNA methylation). CONCLUSIONS: Gut microbiota complexity may correspond with the rate of T cell aging, especially in mid-to-late life. These results suggest an interplay between the gut microbiome and immunological aging that warrants further experimental work.

Slower processing speed after treatment for pediatric brain tumor and acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) and brain tumor (BT) survivors are at risk for post-treatment IQ declines. The extent to which lower scores represent global cognitive decline versus domain-specific impairment remains unclear. This study examined discrepancies between processing speed and estimated IQ (EIQ) scores and identified clinical characteristics associated with score discrepancies in a sample of pediatric cancer survivors. PROCEDURE: Survivors (50 ALL, 50 BT) ages 12-17 years completed cognitive testing. The Wechsler Abbreviated Scale of Intelligence provided an untimed measure of general reasoning ability (EIQ). The age-appropriate Wechsler Intelligence Scale provided a Processing Speed Index (PSI) score. Scores were examined and compared. RESULTS: Survivors' PSI scores were lower than their EIQ scores (BT t(45) =6.3, p<0.001; ALL t(49) =6.9, p<0.001). For BT survivors, lower PSI scores were associated with history of craniospinal irradiation, t(44) =3.3, p<0.01. For ALL survivors, lower PSI scores were associated with male gender, grade retention, and time since diagnosis, F(3, 46) =10.1, p<0.001. Clinically significant EIQ-PSI score discrepancies were identified in 41.3% of BT and 14.0% of ALL survivors. CONCLUSIONS: Many pediatric BT and ALL survivors exhibit slower processing speed than expected for age, whereas general reasoning ability remains largely intact. Risk factors associated with larger EIQ-PSI discrepancies include the following: BT diagnosis, craniospinal irradiation (BT only), male gender, and younger age at diagnosis (ALL only). Grade retention was frequent and associated with lower EIQ scores (both groups) and PSI scores (ALL only). Describing post-treatment cognitive declines using global measures of intellectual ability may underestimate dysfunction or fail to isolate specific underlying deficits contributing to impairment.