TY - JOUR

T1 - Trajectory of reward-related abnormalities in unaffected relatives of patients with bipolar disorder – A longitudinal fMRI study

AU - Macoveanu, Julian

AU - Kjærstad, Hanne Lie

AU - Halvorsen, Kaja Sofie

AU - Fisher, Patrick M.

AU - Vinberg, Maj

AU - Kessing, Lars Vedel

AU - Miskowiak, Kamilla Woznica

N1 - Publisher Copyright: © 2023 The Authors

PY - 2024

Y1 - 2024

N2 - First-degree relatives of patients with bipolar disorder are at heightened risk of mood episodes, which may be attributed to the existence of endophenotypes i.e., heritable (neuro)biological changes present in patients and their unaffected relatives (UR). In this longitudinal MRI study, we aim to investigate the trajectories of aberrant reward-related functional changes identified in UR vs healthy controls (HC). Sixty-eight UR and 65 HC of similar age and gender distribution underwent MRI at baseline while performing a card guessing task. Of these, 29 UR and 36 HC were investigated with the same protocol following a 16-month period in average. We first identified brain regions showing group differences in the neural response to expected value (EV) and reward prediction error (PE) at baseline and analyzed how the reward-related response in these regions changed over time in UR vs HC. Relative to HC at baseline, UR showed lower EV signal in the right ventrolateral prefrontal cortex (vlPFC) and paracingulate gyrus and lower PE signal in the left vlPFC and dorsomedial PFC. The trajectories of these abnormalities in UR showed a normalization of the prefrontal EV signals, whereas the PE signals which correlated with depressive symptoms remained stable over time. While the UR showed both blunted EV and PE signals, none of these abnormalities increased over time, which is consistent with the observed stable mood symptoms.

AB - First-degree relatives of patients with bipolar disorder are at heightened risk of mood episodes, which may be attributed to the existence of endophenotypes i.e., heritable (neuro)biological changes present in patients and their unaffected relatives (UR). In this longitudinal MRI study, we aim to investigate the trajectories of aberrant reward-related functional changes identified in UR vs healthy controls (HC). Sixty-eight UR and 65 HC of similar age and gender distribution underwent MRI at baseline while performing a card guessing task. Of these, 29 UR and 36 HC were investigated with the same protocol following a 16-month period in average. We first identified brain regions showing group differences in the neural response to expected value (EV) and reward prediction error (PE) at baseline and analyzed how the reward-related response in these regions changed over time in UR vs HC. Relative to HC at baseline, UR showed lower EV signal in the right ventrolateral prefrontal cortex (vlPFC) and paracingulate gyrus and lower PE signal in the left vlPFC and dorsomedial PFC. The trajectories of these abnormalities in UR showed a normalization of the prefrontal EV signals, whereas the PE signals which correlated with depressive symptoms remained stable over time. While the UR showed both blunted EV and PE signals, none of these abnormalities increased over time, which is consistent with the observed stable mood symptoms.

KW - Bipolar disorders

KW - Expected value

KW - Longitudinal fMRI

KW - Prediction error

KW - Relatives

KW - Reward

U2 - 10.1016/j.jpsychires.2023.12.035

DO - 10.1016/j.jpsychires.2023.12.035

M3 - Journal article

C2 - 38157669

AN - SCOPUS:85181229346

VL - 170

SP - 217

EP - 224

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

ER -