Bipolar or unipolar? A brain teasing question

During the depressed or remitted states, major depressive disorder (MDD) and bipolar disorder (BD) are difficult to distinguish clinically. Treatments for both disorders differ, and inadequate treatment may lead to chronicity, poor psychosocial functioning, or even suicide. Although early differentiation is important, diagnostic questionnaires or interviews do not adequately differentiate between MDD and BD. Functional and structural MRI (fMRI and sMRI) is becoming increasingly available and may be used to identify disease specific brain processes (biomarkers) for MDD and BD. However, previous studies comparing these disorders often allowed medication use, limiting generalizability and validity. Therefore, in this thesis, we investigated differences in brain function (emotion regulation, cognition, resting state) and structure (volume, gyrification, surface area, thickness) between medication-free MDD and BD. We showed that, at group level, medication-free MDD and BD patients demonstrated differences in brain activity during emotion regulation and planning, as well as differences in brain morphology, both during depression and remission. During a depressive episode, diagnosis could also be predicted at an individual level: based on brain activity during rest and on morphology of emotion regulation areas, diagnosis could be predicted with nearly 70% accuracy. Remitted patients, however, could not be diagnosed at an individual level. In conclusion, medication-free patients with MDD and BD could be distinguished using MRI scans of the brain; furthermore, mood state was important for differentiation at an individual level. However, since sample sizes were small and patients were not medication-naive, more research is needed to assess validity and generalizability of our results.