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Evidence from post-mortem, genetic, neuroimaging, and non-human animal research suggests that Major Depressive Disorder (MDD) is associated with abnormalities in brain myelin content. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc), lateral prefrontal cortex (LPFC), insula, subgenual anterior cingulate cortex (sgACC), and medial prefrontal cortex (mPFC). We examined whether MDD is characterized by reduced myelin at the whole-brain level and in NAcc, LPFC, insula, sgACC, and mPFC. Quantitative magnetic resonance imaging (qMRI) permits the assessment of myelin content, in vivo , in the human brain through the measure of R1. In this study we used qMRI to measure R1 in 40 MDD and 40 healthy control (CTL) participants. We found that the MDD participants had lower levels of myelin than did the CTL participants at the whole-brain level and in the NAcc, and that myelin in the LPFC was reduced in MDD participants who had experienced a greater number of depressive episodes. Although further research is needed to elucidate the role of myelin in affecting emotional, cognitive, behavioral, and clinical aspects of MDD, the current study provides important new evidence that a fundamental property of brain composition, myelin, is altered in this disorder.

Pregnant women may be especially susceptible to negative events (i.e. adversity) related to the coronavirus disease 2019 (COVID-19) pandemic and negative affective responses to these events (i.e. stress). We examined the latent structure of stress and adversity related to the COVID-19 pandemic among pregnant women, potential antecedents of COVID-19-related stress and adversity in this population, and associations with prenatal depressive symptoms. We surveyed 725 pregnant women residing in the San Francisco Bay Area in March-May 2020, 343 of whom provided addresses that were geocoded and matched by census tract to measures of community-level risk. We compared their self-reported depressive symptoms to women matched on demographic factors and history of mental health difficulties who were pregnant prior to the pandemic. Women who were pregnant during the pandemic were nearly twice as likely to have possible depression than were matched women who were pregnant prior to the pandemic. Individual- and community-level factors tied to socioeconomic inequality were associated with latent factors of COVID-19-related stress and adversity. Beyond objective adversity, subjective stress responses were strongly associated with depressive symptoms during the pandemic. Highlighting the role of subjective responses in vulnerability to prenatal depression and factors that influence susceptibility to COVID-19-related stress, these findings inform the allocation of resources to support recovery from this pandemic and future disease outbreaks. In addition to policies that mitigate disruptions to the environment due to the pandemic, treatments that focus on cognitions about the self and the environment may help to alleviate depressive symptoms in pregnant women.

Many psychological disorders are characterized by difficulties in emotion regulation. It is unclear, however, whether different disorders are associated with the use of specific emotion regulation strategies, and whether these difficulties are stable characteristics that are evident even after recovery. It is also unclear whether the use of specific strategies is problematic across all disorders or whether disorders differ in how strongly strategy use is associated with symptom severity. This study investigated (1) the specificity of use of emotion regulation strategies in individuals diagnosed with current major depressive disorder (MDD), with social anxiety disorder (SAD), and in never-disordered controls (CTL); and (2) the stability of strategy use in formerly depressed participants (i.e., remitted; RMD). Path analysis was conducted to examine the relation between strategy use and symptom severity across diagnostic groups. Compared to the CTL group, participants in both clinical groups endorsed more frequent use of rumination and expressive suppression, and less frequent use of reappraisal. Specific to SAD were even higher levels of expressive suppression relative to MDD, as well as a stronger relation between rumination and anxiety levels. In contrast, specific to MDD were even higher levels of rumination and lower levels of reappraisal. Interestingly, elevated rumination, but not decreased reappraisal, was found to be a stable feature characterizing remitted depressed individuals. These results may provide insight into ways in which emotion regulation strategy use maintains psychological disorders.

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

An increasing prevalence of early childhood adversity has reached epidemic proportions, creating a public health crisis. Rather than focusing only on adverse childhood experiences (ACEs) as the main lens for understanding early childhood experiences, detailed assessments of a child’s social ecology are required to assess “early life adversity.” These should also include the role of positive experiences, social relationships, and resilience-promoting factors. Comprehensive assessments of a child’s physical and social ecology not only require parent/caregiver surveys and clinical observations, but also include measurements of the child’s physiology using biomarkers. We identify cortisol as a stress biomarker and posit that hair cortisol concentrations represent a summative and chronological record of children’s exposure to adverse experiences and other contextual stressors. Future research should use a social–ecological approach to investigate the robust interactions among adverse conditions, protective factors, genetic and epigenetic influences, environmental exposures, and social policy, within the context of a child’s developmental stages. These contribute to their physical health, psychiatric conditions, cognitive/executive, social, and psychological functions, lifestyle choices, and socioeconomic outcomes. Such studies must inform preventive measures, therapeutic interventions, advocacy efforts, social policy changes, and public awareness campaigns to address early life adversities and their enduring effects on human potential. Impact Current research does not support the practice of using ACEs as the main lens for understanding early childhood experiences. The social ecology of early childhood provides a contextual framework for evaluating the long-term health consequences of early life adversity. Comprehensive assessments reinforced with physiological measures and/or selected biomarkers, such as hair cortisol concentrations to assess early life stress, may provide critical insights into the relationships between early adversity, stress axis regulation, and subsequent health outcomes.

Suicidal ideation (SI) and non-suicidal self-injury (NSSI) are two distinct yet often co-occurring risk factors for suicide deaths in adolescents. Elucidating the neurobiological patterns that specifically characterize SI and NSSI in adolescents is needed to inform the use of these markers in intervention studies and to develop brain-based treatment targets. Here, we clinically assessed 70 adolescents—49 adolescents with depression and 21 healthy controls—to determine SI and NSSI history. Twenty-eight of the depressed adolescents had a history of SI and 29 had a history of NSSI (20 overlapping). All participants underwent a resting-state fMRI scan. We compared groups in network coherence of subdivisions of the central executive network (CEN), default mode network (DMN), and salience network (SN). We also examined group differences in between-network connectivity and explored brain-behavior correlations. Depressed adolescents with SI and with NSSI had lower coherence in the ventral DMN compared to those without SI or NSSI, respectively, and healthy controls (all ps < 0.043, uncorrected). Depressed adolescents with NSSI had lower coherence in the anterior DMN and in insula-SN (all ps < 0.030, uncorrected), and higher CEN–DMN connectivity compared to those without NSSI and healthy controls (all ps < 0.030, uncorrected). Lower network coherence in all DMN subnetworks and insula-SN were associated with higher past-month SI and NSSI (all ps < 0.001, uncorrected). Thus, in our sample, both SI and NSSI are related to brain networks associated with difficulties in self-referential processing and future planning, while NSSI specifically is related to brain networks associated with disruptions in interoceptive awareness.

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on \"hot\" and \"cool\" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals’ ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (www.psymri.com). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

In the 1960s, Mischel and colleagues developed a simple ‘marshmallow test’ to measure preschoolers’ ability to delay gratification. In numerous follow-up studies over 40 years, this ‘test’ proved to have surprisingly significant predictive validity for consequential social, cognitive and mental health outcomes over the life course. In this article, we review key findings from the longitudinal work and from earlier delay-of-gratification experiments examining the cognitive appraisal and attention control strategies that underlie this ability. Further, we outline a set of hypotheses that emerge from the intersection of these findings with research on ‘cognitive control’ mechanisms and their neural bases. We discuss implications of these hypotheses for decomposing the phenomena of ‘willpower’ and the lifelong individual differences in self-regulatory ability that were identified in the earlier research and that are currently being pursued.

The tendency to engage in depressive rumination is typically measured with the Ruminative Response Styles (RRS) scale. Treynor et al. ( 2003 ) reported that this scale is composed of two 5-item factors, reflection and brooding, and that the brooding but not the reflection factor is associated with more severe depression over time. These two factors were derived using data from a randomly selected community sample, and it is not clear if these factors would be obtained in samples of currently depressed, formerly depressed, and never depressed individuals. We conducted factor analyses on scores on the RRS scale from three such samples. We found support for the distinction between reflection and brooding in never depressed and formerly depressed individuals; we did not obtain this distinct factor structure in the currently depressed sample. We did, however, find evidence of a second factor in the depressed sample that we labeled ‘intentional rumination.’ The results of this study also suggested that an item from the reflection factor should be replaced with another item from the RRS scale. These findings indicate that the distinction between brooding and reflection is blurred in currently depressed individuals.