Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Abstract

BackgroundBipolar disorder I (BD-I) is defined by episodes of mania, depression, and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.MethodsWe first assessed the severity of negative symptoms in 25 euthymic BD-I patients compared to 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral and dorsal striatal activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.ResultsIn BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant ventral and dorsal striatal activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole brain analyses revealed reduced extra-striatal activation in BD-I patients compared to HC and an association between reduced activation of the inferior frontal gyrus and apathy.ConclusionThis study found that in BD-I patients apathy is present to an extent comparable to schizophrenia, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia

“…and similar (Chase et al, 2013;Kirschner, Cathomas, et al, 2020;Smucny et al, 2021) brain responses as compared to control participants have been observed in BD.…”

“…While in schizophrenia findings converge towards reduced striatal activation during the processing of reward, this result is less clear in BD. Thus, depending on the task, task stage (anticipation of reward or reward outcome) and patients' clinical state (depressed, euthymic, manic) increased [6][7][8], decreased [4,[9][10][11][12] and similar [3,13,14] brain responses as compared to control participants have been observed in BD.…”

“…Recent dimensional approaches to psychopathology highlight the continuity between schizophrenia (SZ) and bipolar disorder (BD) at different levels including clinical presentation, brain morphology, genetic markers and brain connectivity (Yamada et al, 2020). Alterations in reward processing have been described in both disorders, but previous literature remains inconclusive concerning continuity in reward processing deficits between the two disorders (Kirschner, Cathomas, et al, 2020; Kirschner, Rabinowitz, et al, 2020; Nielsen et al, 2012; Schreiter et al, 2016). While SZ findings converge towards reduced striatal activation during the processing of reward, this result is less clear in BD.…”

“…While SZ findings converge towards reduced striatal activation during the processing of reward, this result is less clear in BD. Thus, depending on the task, task stage (anticipation of reward or reward outcome) and patients' clinical state (depressed, euthymic, manic) increased (Dutra et al, 2015; Mason et al, 2014; Nusslock et al, 2012), decreased (Abler et al, 2008; Redlich et al, 2015; Schreiter et al, 2016; Schwarz et al, 2020; Trost et al, 2014) and similar (Chase et al, 2013; Kirschner, Cathomas, et al, 2020; Smucny et al, 2021) brain responses as compared to control participants have been observed in BD.…”

Apathy is not associated with reduced ventral striatal volume in patients with schizophrenia

“…We conducted two region of interest (ROI) analyses to investigate the association between apathy and VS as well as apathy and DS volume. We used the same functionally defined VS mask from our previous fMRI studies (Kirschner et al, 2019;Kirschner et al, 2016;Kirschner et al, 2018;Kluge et al, 2018) to allow direct comparison between structural and functional findings (left VS: x,y,z=-12,10,-2, MNI coordinates from Knutson and Greer) (Fig. 3A).…”