First vs recurrent episode symptomatology in Major Depressive Disorder and its relation to brain function and structure: a network approach

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Abstract 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.

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