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Major Depressive Disorder (MDD) entails cognitive dysfunction in many cognitive domains, but it is still uncertain whether such deficits are present in the early stages. The purpose of the study is to determine the cognitive performance in first episode depression (FED) exploring the presence of different cognitive profiles, and the role of cognition in FED at baseline and long-term. Ninety subjects (18-50 years) were included, 50 patients with a FED and 40 healthy controls. Participants were assessed with a neuropsychological battery, covering language, attention, verbal memory, processing speed and executive domains. Neuropsychological group comparisons were performed with MANOVAs. A hierarchical cluster analysis was run to identify clusters of patients with similar neuropsychological performance. Two generalized linear models were built to predict baseline HDRS-17 and changes at 12 months. Patients performed significantly worse than healthy controls in language, attention/working memory, verbal memory, processing speed and executive functioning, with moderate to large effect sizes (0.5 - 1). Two clusters were found: cognitively preserved patients (n=37) and cognitively impaired patients (n=13). Large effect sizes of cognitive impairment in FED were observed between the two cognitive clusters (preserved and impaired). Depressive symptoms at baseline were predicted by verbal memory (p=0.003), while 12-month changes were predicted by executive function (p=0.041) and language (p=0.037). Cognitive performance predicted depressive symptoms at baseline and at follow-up, pointing to the usefulness of cognitive assessment even at the commencement of the illness., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

The habenula (Hb) can play an important role in major depressive disorder (MDD) as it is a key node between fronto-limbic areas and midbrain monoaminergic structures. In vivo neuroimaging studies have shown reductions in Hb volume in a post-mortem sample of patients with affective disorders but findings in unipolar MDD are not consistent. The current study aimed to investigate whether the Hb volume differed between patients with different stages of unipolar MDD and healthy subjects. We also explored differences in grey (GM) and white matter (WM) volumes and potential age and gender effects. High-resolution images were acquired using a 3T-scanner from 95 participants (21 with first-episode MDD; 20 with remitted-recurrent MDD; 20 with treatment-resistant/chronic MDD; and 34 healthy controls).Two researchers blinded to clinical data manually delineated habenular nuclei, with excellent inter-rater agreement. Multivariate analysis of covariance revealed a significant group-by-gender interaction (F9,258=2.22; p=0.02). Univariate effects emerged for Hb-WM volumes (F3,86=3.12; p=0.03) but not for total Hb volumes (F3,86=0.59; p=0.62) or Hb-GM volumes (F3,86=2.01; p=0.12). Women with a first-episode MDD had greater Hb-WM volumes than healthy controls and patients with treatment-resistant/chronic MDD (p<0.01). These findings remained unaltered when controlled for total intracranial volume or medication load. Our results do not support decreased total Hb volumes in unipolar MDD, in patients with first-episode or in patients with long-lasting recurrent or chronic depression. However, the increased Hb-WM volume we observed in women with a first-episode suggests involvement of Hb and its projections in early stages of the recovery process and in the course of MDD., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)