Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12–88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.
Although the intergenerational transmission of risk for depression is well documented, the mechanisms and moderators involved in this transmission of risk from depressed parents to their offspring are not clear. In this review, we discuss the progress that has been made over the past two decades in studying offspring of depressed parents and describe the maladaptive characteristics of these offspring in a diverse range of domains, including clinical, cognitive, and biological functioning. Despite recent advances in this area, there are unresolved questions that warrant further investigation involving the nature of risk transmission from parent to offspring, the specificity of findings to depression, and the role of factors that often accompany depression. We discuss these issues and offer directions for future research that we believe will move the field forward in gaining a better understanding of the relation between parental depression and altered psychobiological functioning in their offspring.
The ability to regulate one's mood state effectively is critical to emotional and physical health. Recent investigations have sought to delineate the neural mechanisms by which individuals regulate mood states and emotions, positing a critical role of a dorsal system that includes the dorsolateral prefrontal cortex and anterior cingulate. This study extended these efforts by examining the neural correlates of retrieving positive autobiographical memories while experiencing a negative mood state in a sample of healthy female adults. We demonstrated that mood-incongruent recall is associated with activation in ventrolateral and ventromedial prefrontal cortices (including orbitofrontal cortex and subgenual cingulate). These findings suggest that mood-incongruent recall differs from other affect regulation strategies by influencing mood through a ventral regulatory network.
Rumination, or negative repetitive thinking, is a significant risk factor for depression and a common and pervasive habit of thought. Using original data from two online surveys of British adults conducted in March 2021 and February 2022, we examine associations between measures of political engagement and the two types of depressive rumination computed from Nolen-Hoeksema's Response Styles Theory: brooding (the maladaptive component that assesses negative aspects of self-reflection) and reflective pondering (the adaptive component focused on problem-solving). We show that (1) higher brooding is associated with lower internal political efficacy and voting; (2) higher reflective pondering is associated with higher external political efficacy; and (3) reflective pondering increases voting propensity for nonpartisans but not for partisans. Thus, while maladaptive rumination is detrimental to political engagement, adaptive rumination appears to be beneficial. Our findings advance our understanding of the role of reflection in democratic citizenship.
Abstract Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. Methods: In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. We targeted two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements. Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition. Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
