March 25, 2019
Childhood maltreatment has a harmful effect on brain structure and increases the risk for unfavorable clinical outcomes in patients with major depression, including recurring depressive episodes, new research suggests.
"Our findings add weight to the notion that maltreated patients might be clinically and neurobiologically distinct from nonmaltreated patients," Nils Opel, MD, of the Department of Psychiatry, University of Munster, Germany, told Medscape Medical News. "Future research should consider that maltreated patients might represent a distinct subgroup that requires specialized attention and care."
The study was published online March 21 in Lancet Psychiatry.
Less Responsive to Treatment?
The study included 110 patients aged 18 to 60 years with major depressive disorder. At baseline, all underwent structural brain MRI and completed the Childhood Trauma Questionnaire to determine the presence and level of childhood maltreatment.
During the 2-year follow-up period, 35 patients were relapse free; 75 patients experienced depression relapse; 48 suffered one relapse; seven had two relapses; and six had three relapses. In addition, 14 participants experienced a remission period of less than 2 months and so were considered to have chronic depression.
Childhood maltreatment was significantly associated with depression relapse during follow-up (odds ratio [OR], 1.035; 95% confidence interval [CI], 1.001 – 1.070; P = .045), the investigators report.
Brain imaging results showed that both childhood maltreatment and future depression relapse were associated with reduced cortical surface area (OR, 0.996; 95% CI, 0.994 – 0.999; P = .001), primarily in the right insula at baseline.
Insular surface area mediated the relationship between childhood maltreatment and future depression relapse. There were no associations between hippocampal volume, maltreatment, and depression relapse.
"Given the impact of the insular cortex on brain functions such as emotional awareness, it's possible that the changes we saw make patients less responsive to conventional treatments," said Opel.
"Future translational and clinical research might consider how individual and neurobiologically informed risk profiles can be used to provide more specialized/custom-tailored treatment options for depressed patients," he added.
Strengths of the study include the large number of participants and the careful assessment of depression relapse over time. A potential limitation is the retrospective assessment of childhood maltreatment, which could be subject to recall bias.
In a linked commentary, Lianne Schmaal, PhD, from the Center for Youth Mental Health at the University of Melbourne, Australia, notes that the findings may suggest that "early life stress results in so-called limbic scars in the form of alterations in cortical surface area, which in turn increase the risk for unfavorable clinical outcomes in major depression.
"A key remaining question is whether, in the sample investigated in the study by Opel and colleagues, the observed reduction in insular surface area reflects a stable trait or normalizes over time with remission of depression, since in their previous study the researchers only reported how longitudinal changes in cortical thickness — but not surface area — fluctuate with depression relapse," Schmaal writes.
This study, she adds, is "an important contribution to our knowledge of mechanisms that confer risk for depression relapse. A better understanding of these mechanisms is crucial to develop or improve risk-adapted interventions for people susceptible to a worse long-term clinical outcome."
The study was funded by the German Research Foundation, the Interdisciplinary Center for Clinical Research, and the Deanery of the Medical Faculty of the University of Munster. The authors and Schmaal have disclosed no relevant financial relationships.