Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions.

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain's reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.

Background Amotivation, or decisional anhedonia, is a prominent and disabling feature of depression. However, this aspect of depression remains understudied, and no prior work has applied objective laboratory tests of motivation in both unipolar and bipolar depression. Methods We assessed motivation deficits using a Progressive Ratio Task (PRT) that indexes willingness to exert effort for monetary reward. The PRT was administered to 96 adults ages 18–60 including 25 participants with a current episode of unipolar depression, 28 with bipolar disorder (current episode depressed), and 43 controls without any lifetime history of Axis I psychiatric disorders. Results Depressed participants exhibited significantly lower motivation than control participants as objectively defined by progressive ratio breakpoints. Both the unipolar and bipolar groups were lower than controls but did not differ from each other. Limitations Medication use differed across groups, and we did not have a separate control task to measure psychomotor activity; however neither medication effects or psychomotor slowing are likely to explain our findings. Conclusions Our study fills an important gap in the literature by providing evidence that diminished effort on the PRT is present across depressed patients who experience either unipolar or bipolar depression. This adds to growing evidence for shared mechanisms of reward and motivation dysfunction, and highlights the importance of improving the assessment and treatment of motivation deficits across the mood disorders spectrum.

Objective Anhedonia is central to multiple psychiatric disorders and causes substantial disability. A dimensional conceptualization posits that anhedonia severity relates to a trans-diagnostic continuum of reward deficits in specific neural networks. Prior investigations of functional connectivity related to anhedonia have focused on case-control comparisons in specific disorders, using region-specific seed-based analyses. Here, the authors explore the entire functional connectome in relation to reward responsivity across a population of adults with hetereogenous psychopathology. Method In a sample of 225 adults from five diagnostic groups (major depressive disorder, n=32; bipolar disorder, n=50; schizophrenia, n=51, psychosis risk, n=39; and healthy controls, n=53), the authors conducted a connectome-wide analysis examining the relationship between a dimensional measure of reward responsivity (reward sensitivity subscale of the Behavioral Activation Scale) and resting-state functional connectivity using multivariate distance-based matrix regression. Results This connectome-wide analysis identified foci of dysconnectivity associated with reward responsivity in the nucleus accumbens (NAc), default mode network (DMN) and cingulo-opercular network (CON). Follow-up analyses revealed dysconnectivity among specific large-scale functional networks and their connectivity with the NAc. Reward deficits were associated with decreased connectivity between the NAc and DMN and increased connectivity between the NAc and CON. In addition, impaired reward responsivity was associated with DMN hyper-connectivity and diminished connectivity between DMN and CON. Conclusions These results emphasize the centrality of the nucleus accumbens in the pathophysiology of reward deficits and suggest that dissociable patterns of connectivity among large-scale networks are critical to the neurobiology of reward dysfunction across clinical diagnostic categories.

Excessive discounting of future rewards has been related to a variety of risky behaviors and adverse clinical conditions. Prior work examining delay discounting in schizophrenia suggests an elevated discount rate. However, it remains uncertain whether this reflects the disease process itself or an underlying genetic vulnerability, whether it is selective for delay discounting or reflects pervasive changes in decision-making, and whether it is driven by specific clinical dimensions such as cognitive impairment. Here we investigated delay discounting, as well as loss aversion and risk aversion, in three groups: schizophrenia (SZ), unaffected first-degree family members (FM), and controls without a family history of psychosis (NC). SZ had elevated discounting, without changes in loss aversion or risk aversion. Contrary to expectations, the FM group did not show an intermediate phenotype in discounting. Higher discount rates correlated with lower cognitive performance on verbal reasoning, but this did not explain elevated discount rates in SZ. Group differences were driven primarily by the non-smoking majority of the sample. This study provides further evidence for elevated discounting in schizophrenia, and demonstrates that steeper discounting is not necessarily associated with familial risk, cannot be wholly accounted for by cognitive deficits, and is not attributable to smoking-related impulsivity.