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Bringing the field of psychiatry forward: Unraveling heterogeneity of Depression

Final Report Summary - HETODEP (Bringing the field of psychiatry forward: Unraveling heterogeneity of Depression)

Major depressive disorder is a psychiatric disorder that often first occurs in adolescence. Because it is associated with a chronic course for many patients, it is also one of the leading causes of disability in Europe, and putting a large burden on European society. Not all depressive disorders are alike in presentation – and potentially- in their underlying biology and etiology. If we can distinguish forms of depression that are biologically different, we could potentially identify new treatment targets. Such knowledge could be the starting point for developing tailored treatments for people with depression.
One of the aims of this proposal was to evaluate the biological underpinnings as well as the clinical course of subtypes of depression, with a main focus on atypical and melancholic/typical depressive subtypes. We found that the longitudinal course of depression was poorer in atypical and melancholic depression than in a subtype of mild severity, and that anxiety and suicidal thoughts persisted somewhat longer in the melancholic subtype compared to the atypical subtype. We have further established that the atypical subtype is a subtype in which dysregulation of metabolic and inflammatory markers play an important role. We have postulated that the term ‘immuno-metabolic’ depression is perhaps a better name for this subtype, which is also characterized by increased appetite and weight gain. One of the metabolic markers of interest is for instance leptin, a hormone secreted by adipose tissue and involved in appetite regulation. Changes in appetite and weight – a key symptom of major depressive disorder- therefore seem of key importance in unraveling the nature of depression, and specifically for atypical depression, as we have shown that the symptom of increased appetite is driving the observed associations between atypical depression with metabolic and inflammatory factors. More importantly, we have shown that the genetic profiles of persons with atypical and melancholic/typical depression seem to differ; with atypical depression having higher polygenic risk scores for BMI, CRP and leptin. Overall, this line of research supporting the idea that stratification of depression in more homogeneous subgroups is important for biological research of depression, and provides important clues for the origin of atypical depression.
A second aim was to analyze ambulatory measurements (ecological momentary assessments [EMA], i.e. data collection of mood states multiple times per a day through smartphones, and actigraphy, collection of body movements through a watch-like activity tracker) from the National Institute of Health (NIMH) family study, and implementation of EMA in the Netherlands Study of Depression and Anxiety (NESDA). As part of the NESDA 9-year follow-up measurement, we conducted an EMA and actigraphy study in a subset of participants. 386 participants were included, of which 375 completed the study protocol. Currently, data is being cleaned and first analyses are being conducted. This rich data will be able to inform us on the mood dynamics, sleep and physical activity patterns in different diagnostic groups. The possibility to link these data to biological parameters and genetics previously collected in NESDA provide possibilities for future high impact publications. Continued collaborations with the NIMH on EMA data has resulted in publications. In collaboration with dr. Merikangas (NIMH), we have contributed to forming an international network of actigraphy researchers in psychiatry (mMARCH). This network has had its first meetings, and will be continued in the future.
During the running period of the CIG award, the awardee has become fully integrated in the research department an research institute; she will get tenured as of November 1st 2017. She has benefitted from training opportunities to improve her skills in teaching, statistics, grants writing and personal development, and is now co-investigator on several grants. She is supervisor to six PhD students, has obtained formal teaching qualifications, has several teaching duties at the Faculty of Medicine, and is the examination coordinator of the Epidemiology Master. She also serves on the Amsterdam Public Health research institute’s Quality committee that aims to stimulate high research quality in the institute, and has played an active role the organization of intervision meetings for postdocs in the department.