Major depressive disorder (MDD) is a significant psychiatric condition, with many affected individuals not gaining remission from conventional treatments, leading to classification as treatment-resistant depression (TRD). This study aimed to investigate the potential of intravenous (IV) ketamine, particularly the S-enantiomer esketamine in nasal spray form, for treating patients with TRD and associated comorbidities. We report three cases of patients with diverse psychiatric and medical backgrounds whom all reported significant symptomatic relief from depressive episodes and suicidal ideation (SI) following esketamine administration. Additionally, esketamine seemed to proffer benefits beyond the primary depressive symptoms, positively impacting other comorbid conditions, such as agitation, self-injurious behavior (SIB), and chronic pain. The goal of this paper is to highlight that while esketamine's primary utility is in addressing TRD, its therapeutic potential may extend to a variety of associated conditions. However, it is crucial to underscore the heterogeneity of MDD, emphasizing the necessity for individualized therapeutic approaches and further research into esketamine's broader applications.

Background: Epigenetic aging, measured through various DNA methylation-based clocks, may have implications for predicting disease risk. However, the sensitivity of different epigenetic clocks that have emerged as biomarkers for biological aging and in predicting physical and mental health outcomes remains uncertain. This study examines the age and sex-adjusted associations between multiple epigenetic age acceleration measures and three key health indicators, including self-rated health, depressive symptoms, and body mass index (BMI), in a nationally representative sample of U.S. middle-aged and older adults. Methods: We analyzed data from 4,018 adults in the 2016 wave of the Health and Retirement Study (HRS), which included several epigenetic age acceleration measures: HORVATH, HANNUM, LEVINE, HORVATHSKIN, LIN, WEIDNER, VIDALBRALO, YANG, ZHANG, BOCKLANDT, GARAGNANI, and GRIMAGE. Linear regression models were used to assess the associations between epigenetic age acceleration and self-rated health (poor health), depressive symptoms, and BMI, adjusting for age and sex. Results: We found significant positive associations between epigenetic age acceleration and worse self-rated health, higher depressive symptoms, and increased BMI. However, these associations varied across different epigenetic clocks, with some measures potentially having more consistent utility for specific health outcomes than others. Conclusion: Epigenetic age acceleration is linked to poorer self-rated health, greater depressive symptoms, and higher BMI, but choosing which epigenetic clock(s) to use is also important. These findings underscore the need to consider multiple epigenetic aging markers when assessing health risks and highlight the potential for particular clocks to serve as more sensitive indicators of physical and mental health outcomes.

Background: Tobacco use remains disproportionately high among low-income and racial-ethnic minority populations. The CEASE program, with its self-help, hybrid/online, and in-person modalities, has demonstrated efficacy in promoting tobacco cessation. However, predictors of successful cessation among participants in these groups remain unclear. Objective: To identify baseline predictors of successful tobacco cessation among low-income and racial-ethnic minority participants in the CEASE program, with a focus on demographic, socioeconomic, behavioral, and psychosocial factors. Methods: Participants were allocated into three intervention arms: self-help, CEASE hybrid/online, and CEASE in-person. Baseline characteristics, including demographics (e.g., age, gender), socioeconomic status (e.g., education, employment), substance use profiles (e.g., cigarette packs per week, use of other tobacco products, menthol tobacco use), physical health (e.g., general health, number of cardiometabolic risk conditions), mental health (e.g., depressive symptoms, perceived stress), perceived social support, and nicotine dependence, were analyzed as potential predictors of cessation success. Multivariable logistic regression models were used to identify factors associated with successful quitting, controlling for the study arm. Results: In addition to the study arm, gender, baseline depression, cardiometabolic conditions, tobacco flavor, and the use of other tobacco products were significant predictors of quit success. Individuals receiving in-person interventions had significantly higher odds of quitting (AOR = 3.79, p < 0.05). Women were significantly less likely to quit compared to men (AOR = 0.24, p < 0.01). Participants with a greater number of cardiometabolic risk conditions were more likely to quit (AOR = 1.93, p < 0.05), while those with higher levels of depression had lower odds of quitting (AOR = 0.61, p < 0.05). Menthol tobacco users were also less likely to quit (AOR = 0.10, p < 0.05). Interestingly, individuals who used other forms of tobacco in addition to cigarettes had increased odds of quitting (AOR = 2.86, p < 0.05). No other factors, including demographic variables (e.g., age), socioeconomic status (e.g., education, marital status), substance use profiles (e.g., cigarette packs per week, NRT use), or nicotine dependence, were significant predictors of cessation success. Conclusion: Baseline self-reported anxiety/depression and depressive symptoms play a critical role in reducing the likelihood of successful tobacco cessation among low-income and racial-ethnic minority participants in the CEASE program. These findings underscore the importance of addressing mental health challenges as part of tobacco cessation interventions to enhance their efficacy. Future research should explore targeted strategies for integrating mental health support into cessation programs to improve outcomes for underserved populations.

Objective: Previous research has underscored the link between allostatic load—a comprehensive indicator of the cumulative physiological burden of chronic stress—and depression. However, there remains a significant gap in understanding how this relationship may differ across race and sex intersectional groups. This study aimed to investigate variations in the association between elevated allostatic load (AL>4) and depression among different race-sex intersectional groups within the general population. Methods: This cross-sectional secondary analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. The analysis included variables such as race, sex, age, socioeconomic status, depression (measured via the Patient Health Questionnaire - PHQ), and allostatic load. Linear regression analyses were conducted to examine the interactions between race and sex with allostatic load, focusing on the likelihood of high depression as the outcome. Results: Across the pooled sample, an allostatic load greater than 4 was significantly associated with increased depression. Notably, an interaction effect was observed between race and AL>4 on depression among women, indicating that non-Hispanic Black women with a high allostatic load exhibited more pronounced depressive symptoms (Beta: 1.09, CI: 0.02-2.61). Conversely, among men, allostatic load greater than 4 neither correlated with nor interacted with race to influence depression levels. Conclusion: The study highlights the critical need to consider allostatic load as a key target for interventions that aim to reduce depression among Black women. These findings underscore the necessity for customized intervention strategies that address the nuanced race-sex disparities in the impact of allostatic load on mental health across populations.