A 17-year neuroimaging study of persons diagnosed with depression as children found differences in white matter in the dorsal cingulum bundle region of the brain compared to persons without depression of similar age. The emergence of these differences was first detected in adolescence. The study was published in Depression and Anxiety.
Depression, or major depressive disorder (MDD), as it is officially called, is one of the most common major mental disorders and a leading cause of disability. Symptoms include diminished interest or pleasure in activities most of the day, changes in appetite resulting in weight loss or gain, loss of energy or increased fatigue, depressed mood most of the day, nearly every day, difficulty thinking, concentrating and making decisions and others.
While much research has been done on psychological and psychiatric aspects of depression, recent studies have focused on structural changes in white matter fibers of the brain in people with depression, particularly in tracts that connect regions involved in responding to and processing emotionally evocative experiences and those involved in regulating such experiences.
Some results indicate that disruptions in the brain region known as the cingulum bundle happen in the course of depression and that this might affect communication between subcortical and cortical limbic regions of the brain. While these findings were in adults, it is less clear whether these disruptions to the white matter of the brain are also present in children.
“We now know that depression can arise as early as the preschool years, but it has not been clear whether the neural and psychological factors associated with depression are the same for kids who develop depression early versus those who develop it in adolescence or adulthood. Thus, we have been interested in understanding whether the neural differences associated with depression are the same or different for folks who develop depression in childhood versus later in life,” explained study author Deanna M. Barch, the Gregory B. Couch Professor of Psychiatry at Washington University and the editor-in-chief of Biological Psychiatry: Global Open Science.
To examine whether a lifetime history of major depression was associated with brain white matter disruption, Barch and her colleagues analyzed part of the data from the Preschool Depression Study, a 17-year longitudinal study involving a total of 306 children and their primary caregivers conducted at the Washington University School of Medicine. Data from 131 of these children were examined in this study.
Children were recruited for participation in the study when they were 3-5 years of age and were each examined at multiple time points throughout their lives. The last waves of examination, waves from which most of the data from the current study comes, were done when children were 13-19 and 15-21 years of age. At age 7-12, children were first invited to participate in the brain imaging portion of the study and this also involved an additional 42 healthy children.
Diagnoses of children were established through up to 10 in-person assessment session with participants and their primary caregivers. Children were first assessed at ages 3-5 and the most recent assessment was when children were 15-21. Assessments used involved the Preschool-Age Psychiatric Assessment (PAPA), Children and Adolescent Psychiatric Assessment (CAPA), Kiddle Schedule for Affective Disorders and others, depending on the age of the children at the time of each assessment. Based on these, researchers created a cumulative depression score and an indicator of current depression severity. Participants also completed up to five magnetic resonance imaging sessions at different points in their lives.
For analysis, children were divided into three groups: 1) healthy controls, with no lifetime history of major depression, 2) lifetime history of major depression with or without additional diagnoses, and 3) youth with a lifetime history of a disorder other than major depression (primarily anxiety). Groups were matched in age, sex, race, relative motion estimates and income-to-needs ratios.
Results showed decreased fractional anisotropy and axial diffusivity in the dorsal cingulum bundle region of the brain in children with major depression. Low values of these indicators point to poor brain white matter integrity and both were associated with cumulative and current depression severity. Increased radial diffusivity of the same brain region was also found to be associated with both depression indicators. These same types of differences were detected in the ventral cingulum region of the brain, but these were associated with greater cumulative depression severity only.
“This is one more piece of evidence that depression starting in early childhood is associated with some of the same types of brain differences as depression that arises later in life, providing more evidence of continuity of depression across the lifespan,” Barch told PsyPost.
“We were somewhat surprised that we did not see more evidence for differences in the uncinate fasciculus given all of the evidence for disruptions in the amygdala in depression,” she added. “It makes me wonder if that is more associated with depression arising later in life or maybe comes with an even longer history of experiencing depression.”
The study provides an important contribution to the knowledge on changes to the structure of the brain related to major depression. However, it should be taken into account that researchers did not have white matter integrity assessments from early childhood and it thus remains unknown whether the observed changes to the brains of children preceded the onset of depression or developed in the scope of it. Neurobiological sources of these changes also remain unknown.
“We do not know exactly when these differences in white matter arise – so it would be important in future studies to have measures prior to children developing depression and then again after,” Barch explained. “That way we can determine whether brain differences like changes in white matter might contribute to risk for depression versus being a consequence of experiencing depression.”
The study, “White matter alterations associated with lifetime and current depression in adolescents: Evidence for cingulum disruptions”, was authored by Deanna M. Barch, Xiao Hua, Sridhar Kandala, Michael P. Harms, Ashley Sanders, Rebecca Brady, Rebecca Tillman, and Joan L. Luby.
