[Sportschosun Jang Jong-ho] It has been shown that simply examining brain functional connectivity before treatment may make it possible to predict how adolescent patients with depression will respond to antidepressants. In other words, the more actively the brain regions responsible for depressive thoughts are connected with areas involved in sensory and cognitive processing before treatment, the greater the reduction in depressive symptoms after medication.
A research team led by Professor Jae Won Kim of the Department of Child and Adolescent Psychiatry at Seoul National University Hospital, along with Professor Moon Young Jang of the Department of Psychiatry at Korea University Guro Hospital and Professor Kyung Hwa Lee of the Biomedical Research Institute (BRI) at Seoul National University Hospital, announced on the 12th that it had analyzed the relationship between brain functional connectivity and antidepressant response by scanning 70 antidepressant-naive adolescents aged 12 to 17 with resting-state functional MRI (rs-fMRI) before treatment.
Adolescent depression, which develops during a period of brain development, can lead to declines in academic and social functioning if not treated promptly, and may also affect mental health in adulthood. That is why finding effective treatment strategies early is important. Adolescents differ from adults in their brain neurobiological mechanisms and tend to report depression through physical symptoms, so their responses to medication also differ. Although first-line treatment with selective serotonin reuptake inhibitors (SSRIs) can sometimes cause drug resistance or side effects, there has been no way to predict this in advance, making the search for new biomarkers urgent.
The research team therefore focused on the brain's default mode network (DMN), which has drawn attention as a predictor of treatment response in adult depression. The DMN is a brain network that becomes active when a person is at rest. It consists of the ventromedial prefrontal cortex, dorsomedial prefrontal cortex, and posterior cingulate cortex, and is closely linked to inward-directed cognitive processes such as self-reflection and rumination, as well as to depression.
The team conducted the study on 70 adolescents with depression who visited the Mood and Anxiety Clinic of Youth (MAY Clinic) at Seoul National University Hospital and had no prior experience with medication treatment. To examine the pure effect of antidepressants, no other psychotherapy, such as cognitive behavioral therapy, was combined. Before treatment began, the patients underwent about 10 minutes of resting-state functional MRI to measure functional connectivity, which indicates how closely different brain regions communicate with one another. They were then given escitalopram, an SSRI, for eight weeks.
As a result, the average depression score, measured by the Children's Depression Rating Scale-Revised (CDRS-R), fell by 15.47 points, from 58.59 before treatment to 43.11 after eight weeks. Patients whose three key DMN regions were more actively connected before treatment with brain areas responsible for bodily sensory processing, such as the insula and postcentral gyrus, and with regions involved in cognitive control, such as the superior marginal gyrus, showed a greater reduction in symptoms.
Specifically, stronger connectivity between the ventromedial prefrontal cortex and the left postcentral gyrus, the ventromedial prefrontal cortex and the left insula, the dorsomedial prefrontal cortex and the right superior marginal gyrus, and the posterior cingulate cortex and the right superior marginal gyrus was associated with a marked reduction in depressive symptoms. All four findings were statistically significant (p<0.001). By contrast, connectivity among regions within the DMN itself had no relation to treatment response.
This suggests that the brain's ability to regulate excessive negative thinking and communicate smoothly with regions that process external stimuli may be a key mechanism behind treatment success. The research team explained that, given the characteristics of adolescents, whose depression often appears as various physical symptoms, the ability to connect with sensory neural networks may be a major factor determining treatment response.
Professor Moon Young Jang of Korea University Guro Hospital said, "Adolescent depression may have neurobiological mechanisms that differ from those of adult depression because of developmental stage characteristics," adding, "These findings provide important clues for understanding and predicting antidepressant treatment response in adolescent depression."
Professor Jae Won Kim of Seoul National University Hospital emphasized, "This study shows that antidepressant response in adolescent depression may be related to individual differences in pre-treatment brain functional connectivity," and added, "With larger-scale studies and the development of predictive models in the future, it may be possible to develop this into a biomarker that helps select more suitable treatment strategies from the early stages of treatment."
Meanwhile, the findings were published in the latest online edition of the international journal Neuropsychopharmacology (IF 7.1).
Jang Jong-ho, bellho@sportschosun.com
