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Background. Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories of unipolar depression ? Our aim was to test DSM categories (MDD, Dysth and DD) in comparison with empirically derived prognostic categories, using a prospectively followed cohort of depressed patients.Method. A large sample (n=804) of out-patients with unipolar depression were derived from a prospective cohort study, the Netherlands Study of Depression and Anxiety (NESDA). Using latent class growth analysis (LCGA), empirically derived 2-year course trajectories were constructed. These were compared with DSM diagnoses and a wider set of putative predictors for class membership.Results. Five course trajectories were identified, ranging from mild severity and rapid remission to high severity and chronic course trajectory. Contrary to expectations, more than 50 % of Dysth and DD were allocated to classes with favorable course trajectories, suggesting that current DSM categories do not adequately represent course trajectories. The class with the most favorable course trajectory differed on several characteristics from other classes (younger age, more females, less childhood adversity, less somatic illnesses, lower neuroticism, higher extraversion). Older age, earlier age of onset and lower extraversion predicted poorest course trajectory.Conclusions. MDD, Dysth and DD did not adequately match empirically derived course trajectories for unipolar depression. For the future classification of unipolar depression, it may be wise to retain the larger, heterogeneous category of unipolar depression, adopting cross-cutting dimensions of severity and duration to further characterize patients.

Course trajectories were more favorable than expected, although comorbidity resulted in poorer course. Neuroticism, physical functioning, and childhood adversity predicted an unfavorable course.

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BackgroundA chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories.MethodsOne hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity).ResultsChronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases.ConclusionsOur findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data.

Subtypes of major depressive disorder were found to be stable across a 2-year follow-up and to have distinct determinants, supporting the notion that the identified subtypes are clinically meaningful.