Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress.

OBJECTIVES: We aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1. METHODS: Healthy young adults ages 18-40 (N=200; 68% female) were recruited from the community. Participants with ELS (N=118) experienced childhood maltreatment, and the majority (n=92) also experienced childhood parental loss. Control participants (N=82) had no history of childhood maltreatment or parental loss. Participants had no current cardiometabolic or thrombotic conditions. Fasting plasma samples were assessed for markers of metabolic risk and total PAI-1 using the Bio-Plex Pro Human Diabetes Panel (Bio-Rad Laboratories). A composite metabolic risk z-score (MetS risk) was computed from the mean standardized z-scores of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL and HLD cholesterol, fasting plasma glucose, and hemoglobin A1c. RESULTS: We found that a history of ELS was linked to both higher PAI-1 levels and a higher MetS risk score. ELS was associated with a higher MetS Z-score in adulthood via increased circulating PAI-1 levels (Average Causal Mediation Effect [ACME]= 0.07, p = 0.036). ELS was also linked to increased PAI-1 levels via greater MetS z-scores (ACME = 0.02, p < 0.001). There was a significant interaction effect of ELS and exercise on PAI-1 levels (p = 0.03), such that engaging in higher levels of daily exercise was linked to lower PAI-1 levels in individuals with ELS. CONCLUSION: Healthy young adults with ELS have elevated PAI-1 levels and metabolic risk scores. Among individuals with ELS, exercise is linked to lower PAI-1 levels, suggesting a potential direction for early intervention.

Changes in Interoception in Mind-body Therapies for Chronic Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Emerging literature has demonstrated deficits in interoception (i.e., the perception of physical sensations from inside the body) in individuals with chronic pain conditions. Mind-body therapies (MBTs) are purported to improve chronic pain in part through improving or restoring interoceptive abilities. The present systematic review and meta-analysis aimed to examine changes in interoception in MBTs for chronic pain conditions. METHODS: A systematic search of PubMed, PsycINFO, Scopus, CINAHL, and ProQuest Dissertation and Theses was conducted from database inception to February 2023. English language intervention studies evaluating the effect of MBTs on interoception in adults with chronic pain conditions were examined. Changes in pain (severity and interference) following treatment were examined as secondary outcomes. RESULTS: A total of 11 studies (10 unique samples) were identified. Meta-analytic results reveal significant improvements in total interoceptive awareness (Becker's d = 1.168, p < .01) as well as improvements in seven of eight subdomains of interoceptive awareness (ds = 0.28 to 0.81). MBTs were also associated with reductions in both pain intensity (d = -1.46, p = .01) and pain interference (d = -1.07, p < .001). CONCLUSIONS: Preliminary research suggests that MBTs demonstrate improvements in interoceptive awareness and reduce pain in adults with chronic pain. Literature on changes in other domains of interoception, such as interoceptive accuracy, following MBTs is severely lacking. Although more rigorous studies are needed to corroborate results, the present findings lay an important foundation for future research to examine interoception as a possible underlying mechanism of MBTs to improve pain outcomes.

Depression and anxiety as mediators of the relationship between sleep disturbance and somatic symptoms among adolescents on a psychiatric inpatient unit.

Background: This study investigated the relationship between sleep disturbance and somatic symptoms among adolescents residing on a psychiatric inpatient unit. Given the evidence that sleep disturbance may precede the onset of depression and anxiety and the clear associations between mood and somatic symptoms, depression and anxiety were considered as potential mediators of this relationship. Gender was tested as a potential moderator of the relationship between sleep disturbance and depression and anxiety, respectively. Method: A convenience sample of 83 adolescents completed a packet of self-report measures after admission to the unit. Measures assessed depression, sleep disturbance, anxiety, and somatic symptoms. Mediation and moderation analyses were conducted using SPSS PROCESS macro. Results: With anxiety included as a covariate, the overall indirect effect of sleep disturbance on somatic symptoms through depression was significant. No significant moderation effects were found, although females reported significantly higher levels of sleep disturbance, depression, anxiety, and somatic symptoms than males. Conclusions: Results indicated that depression mediated the relationship between sleep disturbance and somatic symptoms above and beyond the effects of anxiety. These findings suggest that interventions aimed at reducing the negative effects of sleep disturbance should also target mood in this population. Individual differences including gender should be considered when developing interventions.

Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.

OBJECTIVES: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke. METHODS: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression. RESULTS: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant. CONCLUSIONS: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

Increased Cardiometabolic Risk in Healthy Young Adults With Early Life Stress.

OBJECTIVE: This study aimed to evaluate the relationship between early life stress (ELS) and metabolic risk in healthy young adults and assess the role of health behaviors. METHODS: Young adults aged 18 to 40 years ( N = 190) with no medical conditions or medication usage were recruited from the community. Participants with ELS ( N = 113) had a history of childhood maltreatment, and most also experienced parental loss ( n = 88). Controls ( N = 77) had no history of maltreatment or parental loss. Standardized interviews and self-reports assessed demographics, adversity, medical/psychiatric history, and health behaviors. Blood pressure and anthropometrics were measured, and fasting plasma assayed for lipid profiles, glucose, insulin level, and hemoglobin A 1c . We calculated both a clinical cut-point and continuous composite metabolic risk score based on clinical risk factors and the mean of z scores of each measure, respectively. RESULTS: ELS was significantly associated with increased clinical cut-point ( ß = 0.68, 95% confidence interval [CI] = 0.20-1.17, p = .006) and continuous ( ß = 0.23, 95% CI = 0.08-0.038, p = .003) composite metabolic risk scores. On sensitivity analysis, the association of ELS with the continuous composite metabolic risk score was reduced to a trend after adjusting for a range of psychosocial and health predictors ( ß = 0.18, 95% CI = 0.00-0.36, p = .053), with both diet and college graduate status significant in the model. CONCLUSIONS: Healthy young adults with a history of ELS have increased metabolic risk scores as compared with controls. This relationship may be partially due to health behaviors and socioeconomic factors. These findings underline that ELS is an early contributor to metabolic risk.

Personality predictors of 6-month readmission in adult psychiatric inpatients.

Readmission of psychiatric inpatients is highly prevalent and places a significant financial burden on the healthcare system. Rehospitalisation is often used as a metric of quality of care in psychiatric settings, but little is known about how specific personality traits impact readmission in adult psychiatric inpatients. A convenience sample of 94 adults (mean age = 36.8 years; female = 54.3%; European American = 76.6%) at an inpatient psychiatric hospital completed the Personality Inventory for DSM-5-Brief Form (PID-5-BF; American Psychiatric Association, 2013); demographic and medical information and readmission data were extracted via chart review. Poisson regression was used to predict number of readmissions at 6 months after discharge from PID-5-BF domain scores of Negative Affectivity, Detachment, Antagonism, Disinhibition and Psychoticism. Twenty-three patients (24.5%) were readmitted at least once by 6-month follow-up. Higher PID-5-BF Negative Affectivity domain scores predicted greater number of readmissions at 6 months (incidence rate ratio (IRR) = 1.14, robust standard error (RSE) = 0.05, p < .01, 95% confidence interval [1.04, 1.25]). The other PID-5-BF domain scores were not significantly related to number of readmissions. Thus, greater negative affect, indicative of higher trait neuroticism, heightened experience of negative emotions and poor self-concept, was a significant personality predictor of readmission in the study. These results suggest that assessing this trait domain might help to identify psychiatric inpatients at greater risk for readmission and determine those most in need of enhanced services to reduce rehospitalisation.

The effects of early life stress on reward processing.

Early life stress (ELS), in the form of childhood maltreatment, abuse, or neglect, increases the risk for psychiatric sequelae later in life. The neurobiology of response to early stress and of reward processing overlap substantially, leading to the prediction that reward processing may be a primary mediator of the effects of early life stress. We describe a growing body of literature investigating the effects of early life stressors on reward processing in animals and humans. Despite variation in the reviewed studies, an emerging pattern of results indicates that ELS results in deficits of ventral striatum-related functions of reward responsiveness and approach motivation, especially when the stressor is experienced in early in development. For stressors experienced later in the juvenile period and adolescence, the animal literature suggests an opposite effect, in which ELS results in increased hedonic drive. Future research in this area will help elucidate the transdiagnostic impact of early life stress, and therefore potentially identify and intervene with at-risk youth, prior to the emergence of clinical psychopathology.

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment.

Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus-pituitary-adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3-5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.