Family history of depression is associated with alterations in task‐dependent connectivity between the cerebellum and ventromedial prefrontal cortex

Abstract

Background: 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.Methods: We subdivided 279 participants from the Human Connectome Project into three groups: 71 with a lifetime history of MDD, 103 with a family history (FH) of MDD, and 105 healthy controls (HCs). We then evaluated task-based functional magnetic resonance imaging data on a social cognition and a reward processing task and found a region of the ventromedial prefrontal cortex (vmPFC) that responded to both tasks, independent of the group. To investigate whether the vmPFC shows alterations in functional connectivity between groups, we conducted psychophysiological interaction analyses using the vmPFC as a seed region.Results: We found that FH (relative to HC) was associated with increased sadness scores, and MDD (relative to both FH and HC) was associated with increased sadness and MDD symptoms. Additionally, the FH group had increased vmPFC functional connectivity within the nucleus accumbens, left dorsolateral PFC, and subregions of the cerebellum relative to HC during the social cognition task.Conclusions: These findings suggest that aberrant neural mechanisms among those with a familial risk of MDD may underlie vulnerability to altered social cognition.

Distinct alterations in cerebellar connectivity with substantia nigra and ventral tegmental area in Parkinson’s disease

“…We also provide evidence that the cerebellum may play a significant role in regulating these pathways, consistent with recent work in mice 15 and therefore in the development of neuropsychiatric conditions. A growing body of work links mood disorders such as depression to dysregulated functional connectivity within the cerebellum 36 , 37 . Of note, depression is common in PD 38 ; whether this can be linked to common pathways is a question for future research.…”

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease

“…We also provide evidence that the cerebellum may play a significant role in regulating these pathways, consistent with recent work in mice (D’Ambra et al, 2021) and therefore in the development of neuropsychiatric conditions. A growing body of work links mood disorders such as depression to dysregulated functional connectivity within the cerebellum (Frazier et al, 2021; Tepfer et al, 2021). Of note, depression is common in PD (Reijnders et al, 2008); whether this can be linked to common pathways is a question for future research.…”

Tensorial Independent Component Analysis Reveals Social and Reward Networks Associated with Major Depressive Disorder

“…We used an identical sample as our previous work (Tepfer et al, 2021). Specifically, the sample included 279 participants (males,120;females,159;ages,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)mean ± SD,28.45 ± 3.75 years) from the 1200 Subjects Release (WU-Minn HCP consortium S1200 Data) of the Human Connectome Project (HCP).…”

“…Task-dependent connectivity between the striatum and ACC has been shown to be relatively less for individuals with MDD in response to rewards (Morgan et al, 2016; Admon et al, 2015) and greater in response to social stimuli (Healy et al, 2014). Connectivity has also been shown to be altered between the striatum and vmPFC under depression in response to both rewards (Furman et al, 2011;Hanson et al, 2018) and social stimuli (Tepfer et al, 2021). Though these results suggest that connectivity from the striatum to both the ACC and vmPFC differ for those with MDD, this could either imply that MDD is associated with changes to a single larger network which incorporates each of these areas or two independent networks, one highlighting activity in the striatum and vmPFC and the other striatum and ACC.…”