DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate

Abstract

Background Adolescence is a vulnerable period for the onset of major depressive disorder (MDD). While some studies have shown white matter alterations in adolescent MDD, there is still a gap in understanding how the brain is affected at a network level. Methods We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 57 adolescents with MDD and 41 well-matched healthy controls who completed self-reports of depression symptoms and stressful life events. Using atlas-based brain regions as network nodes and tractography streamline count or mean fractional anisotropy (FA) as edge weights, we examined weighted local and global network properties and performed Network-Based Statistic (NBS) analysis. Results While there were no significant group differences in the global network properties, the FA-weighted node strength of the right caudate was significantly lower in depressed adolescents and correlated positively with age across both groups. The NBS analysis revealed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to frontal gyri, insula, and anterior cingulate. Within this cluster, the most robust difference between groups was the connection between the right caudate and middle frontal gyrus. This connection showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed adolescents. Limitations Use of DTI-based tractography, one atlas-based parcellation, and FA values to characterize brain networks represent this study’s limitations. Conclusions Our results allowed us to suggest caudate-centric models of dysfunctional processes underlying adolescent depression, which might guide future studies and help better understand and treat this disorder.

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: “Training for Awareness Resilience and Action” (TARA)—A Pilot Study

“…Depressed adolescents show disrupted balance of cortico-striatal circuit function, with low striatal response and high medial prefrontal response to reward (45). A recent diffusion MRI-based study also revealed a right caudate-centered sub-network of lower structural connectivity in adolescents with MDD (46). Both acute and chronic stress also appears to increase reward deficits, which, in turn, raises the risk for depression (47).…”

Reduced structural connectivity in Insomnia Disorder

“…This is a non-parametric method used to identify significant differences between groups of networks, while controlling for multiple comparisons that arise from comparing 9 a large number of connections. This method has been used to assess alterations of brain connectivity in a number of neurological and psychiatric disorders, including schizophrenia (Zalesky et al, 2011;Zhang et al, 2015), ADHD (Cocchi et al, 2012;Cao et al, 2013;Silk et al, 2016;Beare et al, 2017), depression (Zhang et al, 2011;Korgaonkar et al, 2014;Long et al, 2015;Sacchet et al, 2016;Tymofiyeva et al, 2017) and epilepsy (Besson et al, 2014). The NBS method controls the family-wise error rate by making the assumption that relevant differences in connectivity between groups are confined to connections that are connected with each other and thus form sub-networks in the larger network.…”

Anhedonia correlates with abnormal functional connectivity of the superior temporal gyrus and the caudate nucleus in patients with first-episode drug-naive major depressive disorder

“…Moreover, DTI studies revealed caudate-centric models of dysfunctional processes underlying adolescent depression (Tymofiyeva et al, 2016). It is possible that differential connectivity patterns may be observed across the caudate and temporal cortex in MDD.…”