Associations of early life stress with leptin and ghrelin in healthy young adults.

BACKGROUND: Childhood adversity is a major risk factor for cardiometabolic health problems. Stress-related changes in diet suggest a role for endocrine factors that influence dietary intake, such as leptin and ghrelin. These hormones influence metabolism and may contribute to the relationship of early adversity, mental, and cardiometabolic health. This study examined levels of leptin and ghrelin in a sample of young adults with and without early life stress (ELS). METHODS: Young adults ages 18-40 (N = 200; 68.5% female) were recruited from the community. Participants with ELS (N = 118) had childhood maltreatment, and a subset, n = 92 (78.0%) also had parental loss, and n = 65 (55.1%) also had a current psychiatric disorder. Control participants (N = 82) had no maltreatment, parental loss, or psychiatric disorders. Standardized interviews and self-reports assessed demographics, adversity, medical/psychiatric history, and health behaviors. Exclusion criteria included medical conditions and current medications other than hormonal contraceptives. Body Mass Index (BMI) and other anthropometrics were measured, and fasting plasma was assayed for total ghrelin and leptin with the Bio-Plex Pro Human Diabetes Panel. RESULTS: While ELS was significantly associated with greater leptin (r = .16, p = .025), a finding which held when adjusted for age and sex (F(3196)= 28.32, p = .011), this relationship was abolished when accounting for BMI (p = .44). Participants with ELS also had significantly lower total ghrelin (r = .21, p = .004), which held adjusting for age and sex (p = .002) and was attenuated (p = .045) when the model included BMI (F=46.82, p < .001). Current psychiatric disorder was also a significant predictor of greater leptin (r = .28, p < .001) and lower ghrelin (r = .29, p = .003). In the model with ELS and covariates, psychiatric disorder remained significant (F=7.26, p = .008) and ELS was no longer significant (p = .87). Associations with severity and recent perceived stress were also examined. CONCLUSION: The relationship of ELS and leptin was no longer significant when accounting for BMI, suggesting potential avenues for intervention. Ghrelin findings persisted after correction for BMI, which may be secondary to physiological differences in the regulation of these hormones (leptin is produced by adipocytes, whereas ghrelin is produced primarily in the GI tract). Lastly, these findings suggest that psychiatric functioning may be a key component contributing to the relationship of lower total ghrelin and childhood adversity.

Effects of transcranial magnetic stimulation on anhedonia in treatment resistant major depressive disorder.

BACKGROUND: Anhedonia is one of the defining features of depression but it remains difficult to target and treat. Transcranial magnetic stimulation (TMS) is a proven treatment for depression, but its effects on anhedonia and whether anhedonia can be used as a predictive biomarker of response is not well known. METHODS: Snaith-Hamilton Pleasure Scale was administered to patients with depression before and after a standard course of TMS in a naturalistic outpatient setting. RESULTS: 144 patients were analyzed. There was an overall significant improvement in anhedonia from pre- to post-treatment (7.69 ± 3.88 vs. 2.96 ± 3.45; p < .001). Significant correlations between improvements in anhedonia and other depressive symptoms were present (r = 0.55, p < .001). Logistic regression revealed that baseline anhedonia severity was not a significant predictor of clinical outcome. CONCLUSION: This is the first large, naturalistic study examining the effects of standard, non-research TMS on anhedonia. Among depressed patients, TMS resulted in significant improvements in anhedonia. Patients with severe baseline anhedonia had an equal chance of achieving clinical response/remission. Patients with anhedonia should not be excluded from treatment if they are safe for outpatient care and otherwise appropriate candidates for treatment.

Do measures of healthy eating differ in survivors of early adversity?

Early life adversity has been linked to poor health, including obesity. Understanding the role of unhealthy food intake, may elucidate the importance of self-soothing behaviors in explaining the association between early life adversity and poor health in adulthood. The purpose of this study was to assess the association between early life adversity and dietary quality in a sample of adults from the Lifestyle Influences of Family Environment study. Early life adversity, demographic, and dietary data were obtained for 145 participants using formal interviews and two days of interviewer-administered 24-h recalls. Dietary quality was measured using the 2015 Healthy Eating Index (HEI) scoring algorithm to compute total and component scores. The association between early life adversity and dietary quality was assessed through linear regression and in models adjusted for age and sex. The mean ± SD HEI score for all participants was 54.6 ± 12.8. Individuals with early life adversity had a 4.51 lower overall HEI score when compared to those without early life adversity, 95% CI (0.35, 8.68). After adjusting for age and sex, early life adversity was associated with a 4.6 lower HEI score, 95% CI (0.45, 8.73). HEI component scores indicated that individuals with early life adversity were significantly more likely to have lower whole grain (0.7 versus 2.4) and total dairy (4.3 versus 6.1) scores compared to those without early life adversity. ELA was associated with lower measures of dietary quality. Results warrant future research on dietary and behavioral factors that underly the association between early life adversity and poor health outcomes.

Stress exposure and psychopathology alter methylation of the serotonin receptor 2A (HTR2A) gene in preschoolers.

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. The HTR2A genotype and methylation of HTR2A were measured at two CpG sites (-1420 and -1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site -1420. Contextual stress was positively associated with -1420 methylation among A homozygotes, but negatively associated with -1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at -1420, but positively associated with methylation at -1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.