First vs recurrent episode symptomatology in Major Depressive Disorder and its relation to brain function and structure: a network approach.
Background: Major Depressive Disorder (MDD) is a prevalent psychiatric disorder. At least half of the patients who recover from a first depressive episode, will experience a relapse. Therefore, understanding the underlying mechanisms supporting relapse is a clinical urgency that could be informed by studying complex brain-behavior associations. Here, we investigated how the relationships between depressive symptomatology and regional brain characteristics differed between people with first depressive episode vs recurrent depression. Methods: We used REST-meta-MDD data from the DIRECT consortium. We focused on comparing global and local network properties between first (n=239) and recurrent episode (n=179) on: (i) symptom network, (ii) brain structural (VBM) and functional networks (ALFF, ReHO), and (iii) integrated symptoms network and brain characteristics using the psychopathology and multimodal network approach. Results: Symptom network analysis showed high values of strength centrality for Insomnia: Early Hours of the Morning and General somatic symptoms at recurrence compared to the first episode. Also, differences in global strength in the integrated symptom-brain network (measured with ReHo metric) (S=2.09 p= 0.042). Finally, we found the edge of specific symptom-brain links, including insomnia and somatic symptoms-, to differ between the first episode and recurrence. Conclusions: For symptom networks, local but not global properties differentiated first from recurrent episode MDD, with specially stronger relations of insomnia and somatic symptoms in recurrent episode depression. For integrated symptom-brain networks, global strength of the network reflecting regional functional integrity (ReHO) was related to recurrence. This suggests that symptoms have relevance for understanding the complex brain-symptom relations underpinning recurrence of depression.