Family History of Depression is Associated with Alterations in Task-Dependent Connectivity between the Cerebellum and Ventromedial Prefrontal Cortex

Abstract

A family history of major depressive disorder (MDD) increases the likelihood of a future depressive episode, which itself poses a significant risk for disruptions in reward processing and social cognition. However, it is unclear whether a family history of MDD is associated with alterations in the neural circuitry underlying reward processing and social cognition. To address this gap, we subdivided 279 participants from the Human Connectome Project into three groups: 71 with a lifetime history of MDD (Dep), 103 with a family history of MDD (Fam), and 105 healthy controls (HC). We found that Fam (relative to HCs) were associated with increased sadness scores, and Dep (relative to both Fam and HC) were associated with increased sadness and MDD symptoms. We then evaluated task-based fMRI data on a social cognition and reward processing task and found a region of the ventromedial prefrontal cortex (vmPFC) that responded to both tasks, independent of group. To investigate whether the vmPFC shows alterations in functional connectivity between groups, we conducted psychophysiological interaction (PPI) analyses using the vmPFC as a seed region. These analyses revealed that Fam groups had increased vmPFC functional connectivity within the nucleus accumbens, left dorsolateral PFC and subregions of the cerebellum relative to HCs during the social cognition task. These findings suggest that aberrant neural mechanisms among those with a familial risk of MDD may underlie vulnerability to altered social cognition.

The Role of Social Reward and Corticostriatal Connectivity in Substance Use

“…To model data across participants, we will employ mixed-effects models (Woolrich et al, 2004) that assess simple main effects of each task construct (e.g., reward anticipation) and also brain-behavior correlations (e.g., reward anticipation and substance use). Our group-level models also will include nuisance regressors to account for individual differences in head motion and data quality, as we have done in our prior work (Smith, Utevsky, et al, 2014;Tepfer et al, 2019). Finally, we will correct for multiple comparisons using permutation-based analyses (Eklund et al, 2016) with cluster-extent thresholding (Woo et al, 2014) and threshold-free cluster enhancement (S. M. Smith & Nichols, 2009).…”

The Role of Social Reward and Corticostriatal Connectivity in Substance Use

“…To model data across participants, we will employ mixed-effects models [ 130 ] that assess simple main effects of each task construct (e.g., reward anticipation) and also brain-behavior correlations (e.g., reward anticipation and substance use). Our group-level models also will include nuisance regressors to account for individual differences in head motion and data quality, as we have done in our prior work [ 131 , 132 ]. Finally, we will correct for multiple comparisons using permutation-based analyses [ 133 ] with cluster-extent thresholding [ 134 ] and threshold-free cluster enhancement [ 135 ].…”