RESUMO
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.
Assuntos
Ansiedade , Cuidadores , Depressão , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Psiconeuroimunologia , Transplante Autólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/psicologia , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/psicologia , Mieloma Múltiplo/terapia , Cuidadores/psicologia , Depressão/imunologia , Depressão/psicologia , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia , Envelhecimento/imunologia , Envelhecimento/psicologia , Qualidade de Vida/psicologiaRESUMO
Even healthy older adults experience gastrointestinal (GI) and neurological changes. In fact, the aging process of these two systems are interrelated due the extensive, multifaceted communication network connecting them, termed the gut-brain axis. Age-related modification of the GI environment can influence the bacterial species that survive and thrive there. Additionally, the lifestyle common to older adults in the West, including sedentariness, polypharmacy, and a poor diet, can compound the effect of aging on the GI tract, gut microbiota, and nervous system. Emerging animal and human findings suggest that GI organisms play a major role in gut-brain communication, ultimately shaping neurological aging trajectories by either helping to maintain nervous system function into late life or promoting pathology. Aging and age-related behaviors help to define the gut microbiota's composition and function, but, conversely, the gut microbiota may help to determine late-life functionality and may be harnessed to limit the prevalence of steep neurological decline and diseases. Focusing primarily on clinical research, this review first defines the gut-brain axis, then details age-related GI and nervous system changes, and discusses the impact of age-related lifestyle factors on the GI and nervous systems. The remainder of this review describes cutting-edge research that positions the gut microbiota as an arbiter of age-related neurological decline.
Assuntos
Envelhecimento/genética , Eixo Encéfalo-Intestino/genética , Microbioma Gastrointestinal/genética , Doenças do Sistema Nervoso/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Promoção da Saúde , Casamento , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Idoso , Adulto , Idoso de 80 Anos ou mais , Casamento/psicologia , Cônjuges/psicologia , Emoções , Frequência CardíacaRESUMO
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.
RESUMO
BACKGROUND: Inflammation can have social consequences, which may be relevant to inflammation's link with depression. The current study tests whether a typhoid vaccine increases feelings of social disconnection and avoidance behavior. METHOD: In two full-day visits at least three weeks apart, 172 postmenopausal breast cancer survivors (Stage I-IIIA) each received a typhoid capsular polysaccharide vaccination and a saline placebo injection in a random sequence. Blood was drawn prior to the injection, as well as every 90 min thereafter for 8 h to assess the inflammatory response (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1Ra). At both visits, women completed the Social Connection Scale at 0 and 8.5 h post-vaccination as well as implicit and explicit social avoidance tasks at 7 h post-vaccination. RESULTS: The typhoid vaccine triggered rises in both inflammatory markers (ps < 0.01), but it did not impact feelings of social connection (p = .32), or performance on the implicit (p = .34) or explicit tasks (p = .37). Inflammatory rises did not predict feelings of social connection (ps > 0.64) or performance on explicit (ps > 0.73) or implicit (ps > 0.88) social avoidance tasks. CONCLUSION: Milder inflammatory stimuli may not affect social processes. Higher levels of inflammation or, relatedly, more sickness symptoms may be necessary to recapitulate prior findings of social avoidance.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Vacinas Tíficas-Paratíficas , Feminino , Humanos , Pessoa de Meia-Idade , Comportamento SocialRESUMO
BACKGROUND: Breast cancer survivors often experience many somatic and cognitive side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers opportunities to either enhance or dampen physical health. PURPOSE: In a secondary analysis of a double-blind randomized controlled trial (RCT) using a typhoid vaccine to assess factors associated with breast cancer survivors' inflammatory responses, we assessed how two specific aspects of emotion regulation, mindfulness, and worry, corresponded to acute changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. METHODS: Breast cancer survivors (N = 149) completed two 8.5-hr visits at a clinical research center. Survivors were randomized to either the vaccine/saline placebo or a placebo/vaccine sequence. Worry and mindfulness questionnaires provided data on trait-level emotion regulation abilities. Fatigue, memory problems, and focus difficulties were assessed via Likert scales six times-once before the injections and then every 90 min for 7.5 hr thereafter. Women also completed a pain sensitivity task and several cognitive tasks at each visit. RESULTS: Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits and irrespective of injection type. Lower mindfulness also corresponded to higher subjective fatigue and hot pain sensitivity and objective ratings. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. CONCLUSION: Results from this study highlight the benefits of adaptive emotion regulation in helping mitigate symptoms associated with breast cancer survivorship.
Breast cancer survivors experience side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers the possibility to either better or worse physical health. This study assessed how two emotion regulation strategies, mindfulness and worry, corresponded to changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. A total of 149 survivors completed 2 day-long visits in the laboratory where they rated their fatigue and memory problems six times across the day, completed cognitive tests, and a pain sensitivity test. Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. Results from this study highlight the benefits of adaptive emotion regulation skills like mindfulness in helping improve the cognitive and physical symptoms commonly experienced by breast cancer survivorship.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Atenção Plena , Feminino , Humanos , Sobreviventes de Câncer/psicologia , Atenção Plena/métodos , Estudos Cross-Over , Sobreviventes/psicologia , Neoplasias da Mama/psicologia , Fadiga/psicologia , Dor/complicações , Qualidade de Vida/psicologiaRESUMO
BACKGROUND: Psychological disorders can substantially worsen physical symptoms associated with breast cancer diagnosis and treatment, reducing survivors' quality of life and increasing recurrence risk. Distress disorders may be particularly detrimental given their physical correlates. Across two studies, we examined the relationship between a distress disorder history and physical symptoms pre- and post-adjuvant treatment - two important periods of the cancer trajectory. METHODS: Breast cancer patients awaiting adjuvant treatment (n = 147; mean age = 52.54) in study 1 and survivors 1-10 years post-treatment (n = 183; mean age = 56.11) in study 2 completed a diagnostic interview assessing lifetime presence of psychological disorders. They also rated their pain, fatigue, physical functioning, and self-rated health. Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. RESULTS: Results from both studies indicated that a distress disorder history was associated with higher pain, fatigue, and sleep difficulties as well as lower self-rated health compared to those without such a history. CONCLUSIONS: These findings suggest that breast cancer survivors with a distress disorder may be particularly at risk for more physical symptoms, poorer sleep, and worse self-rated health both prior to and following adjuvant treatment.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Qualidade de Vida/psicologia , Ansiedade/psicologia , Sobreviventes/psicologia , Dor , Fadiga/epidemiologia , Fadiga/etiologiaRESUMO
The social-signal-transduction theory of depression asserts that people who experience ongoing interpersonal stressors and mount a greater inflammatory response to social stress are at higher risk for depression. The current study tested this theory in two adult samples. In Study 1, physically healthy adults (N = 76) who reported more frequent interpersonal tension had heightened depressive symptoms at Visit 2, but only if they had greater inflammatory reactivity to a marital conflict at Visit 1. Similarly, in Study 2, depressive symptoms increased among lonelier and less socially supported breast-cancer survivors (N = 79). This effect was most pronounced among participants with higher inflammatory reactivity to a social-evaluative stressor at Visit 1. In both studies, noninterpersonal stress did not interact with inflammatory reactivity to predict later depressive symptoms.
Assuntos
Depressão , Estresse Psicológico , Adulto , Humanos , Estudos Longitudinais , Exacerbação dos SintomasRESUMO
BACKGROUND: Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors' satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation. METHOD: Breast cancer survivors (n = 139, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n = 69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6). RESULTS: Within-person multilevel mediation analyses showed that when a survivor's relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p = .001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients. CONCLUSION: The gut environment is a new promising candidate for understanding a relationship's long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Feminino , Humanos , Inflamação , Estudos Longitudinais , Recidiva Local de Neoplasia , Permeabilidade , Satisfação Pessoal , Qualidade de Vida , SobreviventesRESUMO
Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.
Assuntos
Senescência Celular , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Estresse Fisiológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Citocinas , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Colorectal cancer poses a significant threat to both psychological and physical health. This study examined relationships between anxiety and depressive symptoms with pain, fatigue, and inflammation among colorectal patients. METHODS: Colorectal cancer patients (n = 88, stages 0-IV) completed a laboratory-based study visit before undergoing adjuvant cancer treatment. Patients completed questionnaires assessing depressive, anxiety, pain, and fatigue symptoms. A blood sample was also collected to measure c-reactive protein (CRP). Analyses controlled for age, sex, cancer stage, body mass index (BMI), and menopause status. RESULTS: Multiple linear regression analyses showed colorectal patients with higher depressive and anxiety symptoms had greater pain, fatigue, and CRP (ps < 0.03). Approximately one-third of patients with clinically significant depressive (CESD >16) and anxiety symptoms (BAI >16) also had clinically-elevated levels of CRP (>3 mg/L) (ps = 0.02). CONCLUSION: These results extend findings from other cancer subgroups showing heightened symptom burden among patients with depression and anxiety. They also highlight the detrimental role that elevated anxiety and depressive symptoms may play in the physical and biological side effects associated with colorectal cancer.
Assuntos
Neoplasias Colorretais , Depressão , Ansiedade/epidemiologia , Ansiedade/psicologia , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/psicologia , Depressão/psicologia , Fadiga/epidemiologia , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Inflamação , DorRESUMO
BACKGROUND: The Center for Disease Control (CDC) recently named childhood abuse histories as a public health risk. Clear links between abuse histories and inflammation exist. However, it remains unknown how abuse histories impact inflammatory trajectories throughout adulthood. Accordingly, this study assessed inflammatory trajectories across three visits among healthy adults with and without abuse histories. METHOD: In this secondary analysis of data from a longitudinal observational study of cancer survivors and noncancer controls, 157 noncancer controls (Mage = 55.8, range = 32-83) completed the Childhood Experiences Questionnaire (CTQ), providing data on physical, emotional, and sexual abuse prior to age 18. Cytokines interleukin-6 (IL-6), interleukin 1-beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were collected at the baseline visit and two follow-up visits approximately one (M months = 11.52, SD = 4.10) and two years (M months = 23.79, SD = 4.40) later. To represent inflammatory changes, cytokine data at each visit were combined into a composite z-score. Covariates in all analyses included age, biological sex, race, income, body mass index, menopause status, psychological diagnosis history, and medical comorbidities. RESULTS: Compared to their nonabused peers, those who had experienced any type of abuse in childhood demonstrated steeper rises in inflammation across time. Inflammation rose more steeply for individuals with physical and emotional abuse histories compared to those without such histories. CONCLUSION: Overall, these data suggest that childhood abuse histories may quicken age-related increases in inflammation, contributing to accelerated aging, morbidity, and early mortality. These findings provide mechanistic insight into why child abuse is a public health risk.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Maus-Tratos Infantis , Inflamação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Criança , Feminino , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. METHODS: Breast cancer survivors (n = 209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. RESULTS: Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-month posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. CONCLUSIONS: Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Feminino , Humanos , Casamento , Satisfação Pessoal , Qualidade de Vida , Pessoa Solteira , SobreviventesRESUMO
A number of studies have shown that self-rated health reliably predicts mortality. This study assessed the impact of perseveration on self-rated health, physical functioning, and physical symptoms (pain, fatigue, breast cancer symptoms) among breast cancer patients. We hypothesized that cancer-related distress would serve as an intervening variable between both worry and rumination and self-rated health, physical functioning, and physical symptoms. Women (N = 124) who were approximately 7 weeks post-surgery but pre adjuvant treatment completed the Impact of Events Scale, the Penn State Worry Questionnaire, and the Rumination Scale. They also rated their pain, fatigue, physical functioning, and self-rated health using the RAND-36 and breast cancer symptoms with the Breast Cancer Prevention Trial Symptom Checklist (BCPT). Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. Worry was associated with higher cancer-related distress, which in turn predicted greater pain and breast cancer symptoms, poorer physical functioning, and lower self-rated health. Rumination also predicted greater cancer-related distress, which ultimately contributed to greater pain along with poorer physical functioning and self-rated health. Models with fatigue as an outcome were not significant. These findings suggest that perseveration can heighten cancer-related distress and subsequent perceptions of physical symptoms and health among breast cancer patients prior to adjuvant treatment. Perseveration early in the cancer trajectory can adversely increase the impact of a cancer diagnosis and treatment on functioning and quality of life.
Assuntos
Neoplasias da Mama , Ansiedade , Neoplasias da Mama/complicações , Fadiga/etiologia , Feminino , Humanos , Dor , Qualidade de Vida , Inquéritos e QuestionáriosAssuntos
COVID-19 , Heurística , Cognição , Tomada de Decisões , Humanos , Medição de Risco , SARS-CoV-2RESUMO
Stress levels are surging, alongside the incidence of stress-related psychiatric disorders. Perhaps a related phenomenon, especially in urban areas, the human gut contains fewer bacterial species than ever before. Although the functional implications of this absence are unclear, one consequence may be reduced stress resilience. Preclinical and clinical evidence has shown how stress exposure can alter the gut microbiota and their metabolites, affecting host physiology. Also, stress-related shifts in the gut microbiota jeopardize tight junctions of the gut barrier. In this context, bacteria and bacterial products can translocate from the gut to the bloodstream, lymph nodes, and other organs, thereby modifying systemic inflammatory responses. Heightened circulating inflammation can be an etiological factor in stress-related psychiatric disorders, including some cases of depression. In this review, we detail preclinical and clinical evidence that traces these brain-to-gut-to-brain pathways that underlie stress-related psychiatric disorders and potentially affect their responsivity to conventional psychiatric medications. We also review evidence for interventions that modulate the gut microbiota (e.g., antibiotics, probiotics, prebiotics) to reduce stress responses and psychiatric symptoms. Lastly, we discuss challenges to translation and opportunities for innovations that could impact future psychiatric clinical practice.
Assuntos
Microbioma Gastrointestinal , Probióticos , Humanos , Microbioma Gastrointestinal/fisiologia , Função da Barreira Intestinal , Inflamação/etiologia , Encéfalo , Avaliação de Resultados em Cuidados de SaúdeRESUMO
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 (Nâ =â 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 (pâ =â .03). Lower Shannon diversity (pâ =â .05) and richness (pâ =â .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.
Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , RNA Ribossômico 16S/genética , Senescência de Células T , RNA MensageiroRESUMO
BACKGROUND: Dyadic stress theories and research suggest that couples' negative communication patterns threaten immune and emotional health, leaving partners vulnerable to illness. Spouses' relationship perceptions can also color how they see and react to marital discussions. To identify pathways linking distressed marriages to poor health, this study examined how self-reported typical communication patterns augmented discussion-based behavioral effects on spouses' blister wound healing, emotions, and discussion evaluations. METHODS: Married couples completed two 24-hour in-person visits where they had their blood drawn to measure baseline interleukin-6 (IL-6), received suction blister wounds, reported their typical communication patterns (demand/withdraw strategies, mutual discussion avoidance, mutual constructive communication), and engaged in marital discussions. Discussions were recorded and coded for positive and negative behaviors using the Rapid Marital Interaction Coding System (RMICS). Immediately after the discussions, spouses rated their emotions and evaluated the discussion tone and outcome. Wound healing was measured for 12 days. RESULTS: Couples who reported typically using more demand/withdraw or mutual avoidance patterns had higher baseline IL-6, slower wound healing, greater negative emotion, lower positive emotion, and poorer discussion evaluations. In contrast, couples reporting more mutual constructive patterns reported more favorable discussion evaluations. Additionally, couples' more negative and less positive patterns exacerbated behavioral effects: Spouses had wounds that healed more slowly, reported lower positive emotion, and evaluated the discussions less positively if their typical patterns and discussion-based behaviors were more negative and less positive. CONCLUSIONS: Couples' typical communication patterns-including how often they use demand/withdraw, mutual avoidance, and mutual constructive patterns-may color spouses' reactions to marital discussions, amplifying the biological, emotional, and relational impact. These findings help explain how distressed marriages take a toll on spouses' health.
Assuntos
Interleucina-6 , Casamento , Humanos , Casamento/psicologia , Vesícula , Cônjuges/psicologia , Emoções , ComunicaçãoRESUMO
OBJECTIVE: There is mixed evidence about whether omega-3 fatty acids reduce depressive symptoms. We previously reported that 4 months of omega-3 supplementation reduced inflammatory responsivity to a lab-based social stressor. In another study, we showed that those with exaggerated inflammatory responsivity to a social stressor had the greatest depressive symptom increases over time, especially if they experienced frequent social stress. Here we tested whether omega-3 supplementation reduced subthreshold depressive symptoms among those who experienced frequent social stress. METHOD: Healthy, sedentary, generally overweight middle-aged and older adults (N = 138) were randomly assigned to 4 months of pill placebo (n = 46), 1.25 grams per day (g/d) omega-3 (n = 46), or 2.5 g/d omega-3 (n = 46). At a baseline visit and monthly follow-up visits, they reported depressive symptoms and had their blood drawn to assess plasma levels of omega-3 fatty acids. Participants completed the Trier Inventory of Chronic Stress at Visit 2 and the Test of Negative Social Exchange at Visit 3. RESULTS: Among those who were overweight or obese, both doses of omega-3 reduced depressive symptoms only in the context of frequent hostile interactions and social tension, and 2.5 g/d of omega-3 lowered depressive symptoms among those with less social recognition or more performance pressure (ps < .05). Findings were largely corroborated with plasma omega-3 fatty acids. No other social stress or work stress measure moderated omega-3 fatty acids' relationship with depressive symptoms (ps > .05). CONCLUSIONS: Omega-3 fatty acids' antidepressant effect may be most evident among those who experience frequent social stress, perhaps because omega-3 fatty acids reduce inflammatory reactivity to social stressors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Assuntos
Depressão , Ácidos Graxos Ômega-3 , Pessoa de Meia-Idade , Humanos , Idoso , Depressão/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , AntidepressivosRESUMO
Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers' health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16INK4a, and epigenetic age could help to reconcile mixed literature on caregiving's sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes -together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.