BACKGROUND: Chronic pain is one of the most common reasons adults seek medical care in the US, with prevalence estimates ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses, including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies. OBJECTIVE AND DESIGN: The objective of the present study was to use a blended analytical approach of machine learning and regression analyses to evaluate the potential relationship between depression and chronic pain in data from a randomized clinical trial of IMGV in diverse, income disadvantaged patients suffering from chronic pain and depression. METHODS: The analytical approach used machine learning to assess the predictive relationship between depression and pain and identify and select key mediators, which were then assessed with regression analyses. It was hypothesized that depression would predict the pain outcomes of average pain, pain severity, and pain interference. RESULTS: Our analyses identified and characterized a predictive relationship between depression and chronic pain interference. This prediction was mediated by high perceived stress, low pain self-efficacy, and poor sleep quality, potential targets for attenuating the adverse effects of depression on functional outcomes. CONCLUSIONS: In the context of the associated clinical trial and similar interventions, these insights may inform future treatment optimization, targeting, and application efforts in racialized, income disadvantaged populations, demographics often neglected in studies of chronic pain. TRIAL REGISTRATION: NCT from clinicaltrials.gov: 02262377. American Academy of Pain Medicine.

Background Chronic pain is one of the most common reasons adults seek medical care in the US, with estimates of prevalence ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies. Objective and Design The objective of the present study was to use a blended analytical approach of machine learning and regression analyses to evaluate the potential relationship between depression and chronic pain in data from a randomized clinical trial of IMGV in socially diverse, low income patients suffering from chronic pain and depression. Methods This approach used machine learning to assess the predictive relationship between depression and pain and identify and select key mediators, which were then assessed with regression analyses. It was hypothesized that depression would predict the pain outcomes of average pain, pain severity, and pain interference. Results Our analyses identified and characterized a predictive relationship between depression and chronic pain interference. This prediction was mediated by high perceived stress, low pain self-efficacy, and poor sleep quality, potential targets for attenuating the adverse effects of depression on functional outcomes. Conclusions In the context of the associated clinical trial and similar interventions, these insights may inform future treatment optimization, targeting, and application efforts in racially diverse, low income populations, demographics often neglected in studies of chronic pain.

Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied. The current study investigates the role of DNA methylation at FOXP3 Treg-cell-specific demethylated region (TSDR), as a marker of regulatory T (Treg) cells that are important negative regulators of inflammation, and the promoter of tumour necrosis factor-alpha (TNF-alpha) gene, an important pro-inflammatory cytokine, in relation to discrimination stress during pregnancy and depression and anxiety symptomatology. A sample of 148 Latina women residing in the US (mean age 27.6 years) were assessed prenatally at 24-32 weeks' gestation and 4-6 weeks postnatally for perceived discrimination exposure (Everyday Discrimination Scale, EDS), emotional distress (depression, anxiety, perinatal-specific depression), acculturation, and acculturative stress. DNA methylation levels at the FOXP3 and TNFalpha promoter regions from blood samples collected at the prenatal stage were assessed by bisulphite pyrosequencing. Regression analyses showed that prenatal EDS associated with postnatal emotional distress, depression and anxiety symptoms only in those individuals with higher than mean levels of FOXP3 TSDR and TNFalpha promoter methylation; no such significant associations were found in those with lower than mean levels of methylation for either. We further found that these relationships were mediated by TNFalpha only in those with high FOXP3 TSDR methylation, implying that immunosuppression via TNFalpha promoter methylation buffers the impact of discrimination stress on postpartum symptomatology. These results indicate that epigenetic markers of immunosuppression and inflammation play an important role in resilience or sensitivity, respectively, to prenatal stress.

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure. METHODS: Population-based data available through the Massachusetts Integrated Clinical Academic Research Database (MiCARD) were used to retrospectively (2005-2014) examine this relationship and calculate the relative risk of peripartum synthetic oxytocin for the development of postpartum depressive and anxiety disorders in exposed (n = 9,684) compared to unexposed (n = 37,048) deliveries. RESULTS: Among deliveries to women with a history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 36% (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.20-1.55). In deliveries to women with no history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 32% compared to those not exposed (RR: 1.32; 95% CI: 1.23-1.42). CONCLUSIONS: Contrary to our hypothesis, results indicate that women with peripartum exposure to synthetic oxytocin had a higher relative risk of receiving a documented depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic oxytocin exposure.

The use of a variety of neuroanatomical techniques has led to a greater understanding of the adverse effects of stress on psychiatric health. One recent advance that has been particularly valuable is the development of resting state functional connectivity (RSFC) in clinical studies. The current study investigates changes in RSFC in F1 adult female rats exposed to the early life chronic social stress (ECSS) of the daily introduction of a novel male intruder to the cage of their F0 mothers while the F1 pups are in the cage. This ECSS for the F1 animals consists of depressed maternal care from their F0 mothers and exposure to conflict between their F0 mothers and intruder males. Analyses of the functional connectivity data in ECSS exposed adult females versus control females reveal broad changes in the limbic and reward systems, the salience and introspective socioaffective networks, and several additional stress and social behavior associated nuclei. Substantial changes in connectivity were found in the prefrontal cortex, nucleus accumbens, hippocampus, and somatosensory cortex. The current rodent RSFC data support the hypothesis that the exposure to early life social stress has long term effects on neural connectivity in numerous social behavior, stress, and depression relevant brain nuclei. Future conscious rodent RSFC studies can build on the wealth of data generated from previous neuroanatomical studies of early life stress and enhance translational connectivity between animal and human fMRI studies in the development of novel preventative measures and treatments.

Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety.