A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.

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ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

The ABCD study: understanding the development of risk for mental and physical health outcomes.

Neural Correlates Associated With Suicide and Nonsuicidal Self-injury in Youth.

Alterations in regional subcortical brain volumes have been widely investigated as part of the efforts of an international consortium, ENIGMA, to determine reliable structural brain signatures for Major Depressive Disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work to precisely map 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 MDD had lower surface area in the subiculum of the hippocampus, the basolateral amygdala, and the nucleus accumbens shell. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum of the hippocampus and the basolateral amygdala. Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala. 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.

https://biorxiv.org/content/biorxiv/early/2019/02/01/534370.full-text.pdf

Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group

Suicide is a major public health concern and a leading cause of death in the US. Alcohol and opioid use disorders (AUD/OUD) significantly increase risk for suicidal ideation, attempts, and death, and are the two most frequently implicated substances in suicide risk. We provide a brief overview of shared risk factors and pathways in the pathogenesis of AUD/OUD and suicidal thoughts and behaviors. We also review clinical recommendations on inpatient care, pharmacotherapy, and psychotherapeutic interventions for people with AUD/OUD and co-occurring suicidal ideation and behavior. Among people with an underlying vulnerability to risk-taking and impulsive behaviors, chronic alcohol intoxication can increase maladaptive coping behaviors and hinder self-regulation, thereby increasing the risk of suicide. Additionally, chronic opioid use can result in neurobiological changes that lead to increases in negative affective states, jointly contributing to suicide risk and continued opioid use. Despite significantly elevated suicide risk in individuals with AUD/OUD, there is a dearth of research on pharmacological and psychosocial interventions for co-occurring AUD/OUD and suicidal ideation and behavior. Further research is needed to understand the effects of alcohol and opioid use on suicide risk, as well as address notable gaps in the literature on psychosocial and pharmacological interventions to lower risk for suicide among individuals with AUD/OUD.

/pdf/suicide-risk-and-addiction-the-impact-of-alcohol-and-opioid-3fv15w74l5.pdf

Suicide Risk and Addiction: The Impact of Alcohol and Opioid Use Disorders

Objective Children of parents with depression are two to three times more likely to develop major depressive disorder than children without parental history; however, subcortical brain volume abnormalities characterizing major depressive disorder risk remain unclear. The Adolescent Brain and Cognitive Development (ABCD) Study provides an opportunity to identify subcortical differences associated with parental depressive history. Method Structural magnetic resonance data were acquired from 9- and 10-year-old children (N = 11,876; release 1.1, n = 4,521; release 2.0.1, n = 7,355). Approximately one-third of the children had a parental depressive history, providing sufficient power to test differences in subcortical brain volume between low- and high-risk youths. Children from release 1.1 were examined as a discovery sample, and we sought to replicate effects in release 2.0.1. Secondary analyses tested group differences in the prevalence of depressive disorders and clarified whether subcortical brain differences were present in youths with a lifetime depressive disorder history. Results Parental depressive history was related to smaller right putamen volume in the discovery (release 1.1; d = −0.10) and replication (release 2.0.1; d = −0.10) samples. However, in release 1.1, this effect was driven by maternal depressive history (d = −0.14), whereas in release 2.0.1, paternal depressive history showed a stronger relationship with putamen volume (d = −0.09). Furthermore, high-risk children exhibited a near twofold greater occurrence of depressive disorders relative to low-risk youths (maternal history odds ratio =1.99; paternal history odds ratio = 1.45), but youths with a lifetime depressive history did not exhibit significant subcortical abnormalities. Conclusion A parental depressive history was associated with smaller putamen volume, which may affect reward learning processes that confer increased risk for major depressive disorder.

Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study

Background Given low base rates of suicidal thoughts and behaviors (STBs) in national samples of adolescents, clarifying the sociodemographic and clinical correlates among psychiatric inpatients may afford insights into potential risk factors that predict STBs onset. Method Adolescents (N = 970; ages 12-19 years) admitted for acute, psychiatric inpatient care completed baseline clinical interviews and self-report measures assessing demographics and early life adversity. Lifetime and 12-month STBs prevalence were obtained, allowing for the estimate of STBs persistence (i.e., rates of those with both current and past STBs) and transition rates (i.e., proportion of ideators that transition to plans or attempts). Univariate and multivariate logistic regression tested sociodemographic and clinical correlates of STBs. Results Age-of-onset for STBs occurred in early adolescence. Most patients reported suicide ideation with nearly half of patients making a plan and one-third a suicide attempt. Although relatively modest, the strongest correlates of lifetime attempts were depressive disorders, physical abuse, and non-suicidal self-injury. Knowing a peer that had attempted suicide also increased the likelihood of a suicide attempt, especially among attempters who transitioned from ideation to planned attempts. Conclusion STBs are highly prevalent among adolescents admitted for acute psychiatric inpatient treatment. The modest effects suggest that correlates, particularly those related to suicide attempts, are widely distributed. As a history of physical abuse and knowing a peer with a suicide attempt history are related to transitioning from ideation to action, these may be critical factors to target in the deployment of future suicide prevention and treatment programs. HIGHLIGHTSOne-third of adolescent inpatients report a lifetime history of suicide attempts.Approximately 65% of adolescent inpatients with a lifetime plan attempt suicide.Knowing peers who attempt suicide may facilitate the transition from ideation to action.

Kira L. Alqueza

Papers

Neural Correlates Associated With Suicide and Nonsuicidal Self-injury in Youth.

Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study

Suicidal Thoughts and Behaviors Among Adolescent Psychiatric Inpatients

Depression risk factors and affect dynamics: An experience sampling study.

Non-suicidal Self-injurious Thoughts and Behaviors Among Adolescent Inpatients.