Mood, Brain, and Development Unit

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

Depression is the leading cause of disability among young people, and by the year 2030, it is projected to be the leading cause of disease burden worldwide (WHO, 2014). Rates of depression increase dramatically during adolescence: 20% of youths experience a major depressive episode before age 18 (Kessler et al., 1994; Beesdoet al., 2009), and five-year relapse rates approach 60% (Dunn & Goodyer, 2006). Longitudinal research suggests strong continuity of adolescent depression into adulthood, with persistent impairments in social and occupational functioning and markedly elevated risk of suicide attempts (Costello et al., 2002; Weissman et al., 1999). This research suggests that most instances of major depression in adults follow from instances of depression or associated mental illnesses during childhood or adolescence. Yet, compared to many other medical conditions, we know little about the mechanisms underlying adolescent depression. Moreover, very few studies attempt to utilize understandings of mechanisms to generate novel treatments. In recent years, reward processing has emerged as a mechanism that could plausibly underlie several key behavioral and neural aberrations observed in depression (Treadway & Zald 2011; Whitton et al., 2015). Work covered under this progress report involved a major transition, with the departure of Dr. Stringaris and the change in Dr. Pine's role, from collaborator to principal investigator. Despite this change, some strong continuities remain between the work performed in the protocol under Dr. Stringaris's and Dr. Pine's leadership. Thus, studies on reward processing continue to play a major role in the work completed for this progress report. During the past year, many important papers target this line of questioning. Some of these papers report new methods that can be used to probe the way in which the brain shapes peoples responses to rewards. Other papers describe how the processing of rewards differs in healthy people and people with major depression. Other areas of continuity involve studies on the course of depressive symptoms in adolescence. Indeed, studies under this progress report led to an important publication that describes changes in symptoms during the pandemic among adolescents treated for major depressive disorder. During the past year, two important changes occurred that will influence future work completed under this progress report. First, work under the progress report will extend studies of mechanism beyond reward-processing mechanisms. This will involve an increasingly deep focus on the role of social stressors in the pathophysiology of major depressive disorder. Such a focus melds ongoing studies in Dr. Pines other studies, as covered in other progress reports. Such a focus also will begin to incorporate therapies, such as interpersonal therapy (IPT), designed to target social stressors in adolescents with major depressive disorder. Second, work under the progress report will involve studies using transcranial magnetic stimulation (TMS), an effective therapy for treatment-resistant depression in adults. During the past year, as part of this progress report, the team effectively designed a novel TMS study and received approval from the Food and Drug Association (FDA) to initiate this work. The team is currently working with the IRB so that the study can be approved, with plans to begin the work early in 2023. The past year brought both continuation of the work described in prior years under this protocol and initiation of new studies. In both areas, the work addresses one of the most important public health problems facing modern society.