Professor Brenda Penninx works at Amsterdam UMC connected to the Vrije Universiteit. Since 2004 she is the principal investigator of the Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl). Her scientific focus is on etiology, course and consequences of depressive and anxiety disorders, and she translates observational research findings in novel intervention studies. Penninx has published over 900 scientific papers. She supervises a research group containing >25 PhD-students, postdocs and assistant professors. Penninx is member of the Royal Dutch Academy of Sciences, of which she serves as vice-president since 2022.

Abstract:

The burden on society by depression is undisputable. This large burden is partly due to a course pattern that is more chronic than often assumed, and the large heterogeneity of depression contributes to non-response to our standardly available treatments. Using data from the NESDA project, Penninx will illustrate both points. NESDA has followed >3400 adults, including many patients with depression and/or anxiety disorders, over 13 years of follow-up. When looking at its long-term course, especially when also considering the transitions between affective disorders, chronicity seems to be more the rule than the exception (Verduijn et al. BMC Med 2017). Taking heterogeneity of depression into account could lead to precision psychiatry approaches that help reduce depression’s chronicity. Using NESDA data, Penninx’s team has consistently found that immuno-metabolic dysregulations vary as a function of depression heterogeneity: dysregulations map more consistently to “atypical” neurovegetative symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis). Such findings are confirmed when utilizing genetic data, including genome-wide gene expression as well as DNA information (Milaneschi et al. Biol Psychiatry 2020). Some preliminary treatment studies further suggest that the presence of immuno-metabolic dysregulations in depressed persons may moderate antidepressant effects of standard or novel (immunomodulatory) interventions. So, an immuno-metabolic depression dimension could dissect depression’s heterogeneity and potentially match depressed subgroups to treatments with higher likelihood of clinical success. Overall, NESDA findings also point out the relevance of dissecting the heterogenous group of depressed persons so that personalized medicine strategies could contribute to reducing the chronic nature and disease burden of depression.