Large Individual Differences in Functional Connectivity in the Context of Major Depression and Antidepressant Pharmacotherapy

Abstract

Clinical studies of major depression (MD) often examine differences between groups whilst ignoring within-group variation. However, inter-individual differences in brain function are increasingly recognised as important and may impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2 and 8 weeks during which patients received pharmacotherapy (escitalopram, N=68), and controls (N=39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs non-responders, female vs male participants), recording sessions and individuals. Individual differences and common connectivity across groups, sessions and participants contributed most to the explained variance (>95% across analyses). Group differences related to MD diagnosis, treatment response and biological sex made significant but small contributions (0.3-1.2%). High individual variation was present in multimodal association areas, while low individual variation characterized primary sensorimotor regions. Group differences were much smaller than individual differences in the context of MD and its treatment. These results could be linked to the variable findings and difficulty translating research on MD to clinical practice. Future research should examine brain features with low and high individual variation in relation to psychiatric symptoms and treatment trajectories to explore the clinical relevance of the individual differences identified here.

One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response

“…Individual differences in functional connectomes accounted for >40% of the explained variance in the data. Group differences were significant but much smaller for sex, depression diagnosis and its treatment which accounted for only about 5% of the variance together ( 25 , preprint). These results underscore the importance of exploring individual variation in relation to group findings in psychiatric research.…”

“…Based on the most consistently reported findings from previous literature, we expected that as a group, responders would exhibit decreased connectivity at lower frequencies (delta, theta and alpha) with treatment, and decreased complexity in response to pharmacotherapy ( 6 , 7 , 9 , 16 ). Based on our work quantifying individual differences in MD with fMRI ( 25 , preprint), we expected significant individual variation around the patterns found in responder and non-responder groups. Here we map what this variation looks like.…”