TY - JOUR
T1 - Decreased reward circuit connectivity during reward anticipation in major depression
AU - Geugies, Hanneke
AU - Groenewold, Nynke A.
AU - Meurs, Maaike
AU - Doornbos, Bennard
AU - de Klerk-Sluis, Jessica M.
AU - van Eijndhoven, Philip
AU - Roest, Annelieke M.
AU - Ruhé, Henricus G.
N1 - Funding Information: The authors are very grateful for the contributions of all the participants, and in addition for the contributions of all students, physicians, psychologists, and nurses of the institutions that were involved in the recruitment of participants for the DIP study: University Medical Center Groningen (department of Psychiatry) and Lentis Groningen (Center for Integral Psychiatry and Old Age Psychiatry). The present work was supported by scholarships from the Research School of Behavioural and Cognitive Neurosciences (M. Meurs and N.A. Groenewold), the Mandema Stipend (B. Doornbos) and a stipend from the Gratama Stichting (N.A. Groenewold). H.G. Ruhé was supported by a NWO/ZonMW VENI-grant (#016.126.059). Publisher Copyright: © 2022 The Authors
PY - 2022/1/1
Y1 - 2022/1/1
N2 - An important symptom of major depressive disorder (MDD) is the inability to experience pleasure, possibly due to a dysfunction of the reward system. Despite promising insights regarding impaired reward-related processing in MDD, circuit-level abnormalities remain largely unexplored. Furthermore, whereas studies contrasting experimental conditions from incentive tasks have revealed important information about reward processing, temporal difference modeling of reward-related prediction error (PE) signals might give a more accurate representation of the reward system. We used a monetary incentive delay task during functional MRI scanning to explore PE-related striatal and ventral tegmental area (VTA) activation in response to anticipation and delivery of monetary rewards in 24 individuals with MDD versus 24 healthy controls (HCs). Furthermore, we investigated group differences in temporal difference related connectivity with a generalized psychophysiological interaction (gPPI) analysis with the VTA, ventral striatum (VS) and dorsal striatum (DS) as seeds during reward versus neutral, both in anticipation and delivery. Relative to HCs, MDD patients displayed a trend-level (p = 0.052) decrease in temporal difference-related activation in the VS during reward anticipation and delivery combined. Moreover, gPPI analyses revealed that during reward anticipation, MDD patients exhibited decreased functional connectivity between the VS and anterior cingulate cortex / medial prefrontal cortex, anterior cingulate gyrus, angular/middle orbital gyrus, left insula, superior/middle frontal gyrus (SFG/MFG) and precuneus/superior occipital gyrus/cerebellum compared to HC. Moreover, MDD patients showed decreased functional connectivity between the VTA and left insula compared to HC during reward anticipation. Exploratory analysis separating medication free patients from patients using antidepressant revealed that these decreased functional connectivity patterns were mainly apparent in the MDD group that used antidepressants. These results suggest that MDD is characterized by alterations in reward circuit connectivity rather than isolated activation impairments. These findings represent an important extension of the existing literature since improved understanding of neural pathways underlying depression-related reward dysfunctions, may help currently unmet diagnostic and therapeutic efforts.
AB - An important symptom of major depressive disorder (MDD) is the inability to experience pleasure, possibly due to a dysfunction of the reward system. Despite promising insights regarding impaired reward-related processing in MDD, circuit-level abnormalities remain largely unexplored. Furthermore, whereas studies contrasting experimental conditions from incentive tasks have revealed important information about reward processing, temporal difference modeling of reward-related prediction error (PE) signals might give a more accurate representation of the reward system. We used a monetary incentive delay task during functional MRI scanning to explore PE-related striatal and ventral tegmental area (VTA) activation in response to anticipation and delivery of monetary rewards in 24 individuals with MDD versus 24 healthy controls (HCs). Furthermore, we investigated group differences in temporal difference related connectivity with a generalized psychophysiological interaction (gPPI) analysis with the VTA, ventral striatum (VS) and dorsal striatum (DS) as seeds during reward versus neutral, both in anticipation and delivery. Relative to HCs, MDD patients displayed a trend-level (p = 0.052) decrease in temporal difference-related activation in the VS during reward anticipation and delivery combined. Moreover, gPPI analyses revealed that during reward anticipation, MDD patients exhibited decreased functional connectivity between the VS and anterior cingulate cortex / medial prefrontal cortex, anterior cingulate gyrus, angular/middle orbital gyrus, left insula, superior/middle frontal gyrus (SFG/MFG) and precuneus/superior occipital gyrus/cerebellum compared to HC. Moreover, MDD patients showed decreased functional connectivity between the VTA and left insula compared to HC during reward anticipation. Exploratory analysis separating medication free patients from patients using antidepressant revealed that these decreased functional connectivity patterns were mainly apparent in the MDD group that used antidepressants. These results suggest that MDD is characterized by alterations in reward circuit connectivity rather than isolated activation impairments. These findings represent an important extension of the existing literature since improved understanding of neural pathways underlying depression-related reward dysfunctions, may help currently unmet diagnostic and therapeutic efforts.
UR - http://www.scopus.com/inward/record.url?scp=85139846266&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nicl.2022.103226
DO - https://doi.org/10.1016/j.nicl.2022.103226
M3 - Article
C2 - 36257119
SN - 2213-1582
VL - 36
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 103226
ER -