Abstract
Youth at familial risk for bipolar disorder (BD-risk) and major depressive disorder (MDD-risk) have aberrant reward processing, a core feature of these mood disorders. Whether BD risk differentiates from MDD risk in reward processing merits further study. We compared neural activation and connectivity during anticipation and outcome of monetary gain and loss during fMRI using the Monetary Incentive Delay (MID) Task among BD-risk (n = 40), MDD-risk (n = 41), and healthy comparison youth (HC) (n = 45), in the absence of any lifetime or current history of psychopathology [mean age 13.09 ± 2.58, 56.3% female]. Participants completed the MID task at baseline and were followed for behavioral and clinical outcomes over 4.37 ± 2.29 years. Region-of-interest (ROI) analyses conducted using anatomically defined thalamus, ventrolateral prefrontal cortex, nucleus accumbens, and putamen seeds showed that relative to MDD-risk and HC, BD-risk had decreased activation of the thalamus during anticipation of monetary gain [F(2,118) = 4.64, p = 0.01 (FDR-corrected p = 0.04)]. Psychophysiological interaction analyses revealed that BD-risk had less connectivity between the thalamus and left middle frontal gyrus (Z > 3.1, p < 0.001) and left-superior temporal gyrus (Z > 3.1, p < 0.05) compared with MDD-risk. Voxelwise, BD-risk had decreased activation in the cerebellum during anticipation and outcome of monetary gain relative to MDD-risk and HC (Z > 3.1, p < 0.001; Z > 3.1, p < 0.01). In BD-risk, decreased thalamic connectivity was associated with increased impulsivity at baseline and reduced prosocial behavior at follow-up. Reduced thalamic activation and connectivity during reward processing may distinguish familial risk for BD from familial risk for MDD and represent early markers of vulnerability that may herald social dysfunction later in adolescence.
Highlights
Bipolar disorder (BD) and major depressive disorder (MDD) are serious and persistent conditions that when developed during childhood and adolescence [1, 2] result in worse outcomes compared with adult onset [3, 4]
We previously described networks of regions implicated in differentiating BD risk from MDD risk during emotion processing [39], and neural markers of reward function in healthy offspring of parents with BD [25]
Dysfunction in youth with mood disorders is associated with significant functional impairments over time [5, 41,42,43], we examined whether neural differences between BD-risk and MDD-risk were related to impulsivity, novelty-seeking, and behavioral strengths and difficulties, or conversion to psychopathology at longitudinal follow-up approximately 4.4 years after baseline
Summary
Bipolar disorder (BD) and major depressive disorder (MDD) are serious and persistent conditions that when developed during childhood and adolescence [1, 2] result in worse outcomes compared with adult onset [3, 4]. Reward-processing dysfunction is a core feature of BD and MDD [5, 6]. Whereas anhedonia is a transdiagnostic symptom manifestation of reward dysfunction that may be observed in MDD and BD [7, 8], hedonism is a distinct feature of BD [9, 10]. Initial depressive presentations of these disorders may overlap, familial aggregation patterns [11] and nonoverlapping symptoms suggest distinct disruptions in reward processes. Transdiagnostic reward deficits that point to common illness features can lead to delays in accurate diagnosis and appropriate treatment. Elucidating reliable, early reward-processing deficits distinguishing BD from MDD would provide insights for unique predisposing factors for symptom trajectories and lead to more refined approaches to accurate diagnosis and treatment selection
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