Reward dysfunction in major depression: Multimodal neuroimaging evidence for refining the melancholic phenotype

Reward dysfunction is thought to play a core role in the pathophysiology of major depressive disorder (MDD). Event-related potential (ERP) and functional magnetic resonance imaging (fMRI) studies have identified reward processing deficits in MDD, but these methods have yet to be applied together in a single MDD sample. We utilized multimodal neuroimaging evidence to examine reward dysfunction in MDD. Further, we explored how neurobiological reward dysfunction would map onto subtypes of MDD. The feedback negativity (FN), an ERP index of reward evaluation, was recorded in 34 unmedicated depressed individuals and 42 never-depressed controls during a laboratory gambling task. Ventral striatal (VS) activation to reward was recorded in a separate fMRI session, using an identical task, among a subgroup of 24 depressed individuals and a comparison group of 18 non-depressed controls. FN amplitude was blunted in MDD. This effect was driven by a MDD subgroup characterized by impaired mood reactivity to positive events, a core feature of melancholic MDD. A similar pattern was observed for VS activation, which was also blunted among the MDD subgroup with impaired mood reactivity. Neither FN amplitude nor VS activation were related to the full, DSM-defined melancholic or atypical MDD subtypes. Across the MDD sample, FN amplitude and VS activation were correlated, indicating convergence across methods. These results indicate that not all MDD is characterized by reward dysfunction, and that there is meaningful heterogeneity in reward processing within MDD. The current study offers neurobiological evidence that impaired mood reactivity is a key phenotypic distinction for subtyping MDD, and further suggests that the existing melancholic phenotype may require further refinement

An incongruent reality: The N400 in relation to psychosis and recovery

BACKGROUND: Cognitive impairments and delusions are hallmarks of schizophrenia, and are thought to be due in part to abnormalities in semantic priming. The N400, a neural measure of semantic processing, is found to be reduced in schizophrenia. However, it is unclear if individuals with other psychoses (e.g., mood disorders or substance abuse with psychotic features) also show this impairment, and whether N400 reduction relates to real-world functioning and recovery. METHODS: Eighty-nine individuals from the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis, and 35 healthy adults were assessed using matched, related, and unrelated picture-word pairs to elicit the N400. Patients' real-world functioning, symptomatology, and recovery were tracked since first hospitalization; EEG assessment was completed during year 15 of the study. RESULTS: Participants with schizophrenia had slower reaction times and reduced N400 to semantically incongruent stimuli relative to healthy participants. Schizophrenia and other psychoses did not differ on N400, suggesting that N400 abnormalities characterize psychosis broadly. When grouped by recovery status, patients who remained ill had a significantly blunted N400, while those who recovered did not differ from healthy adults. Few patients with schizophrenia achieved recovery; therefore recovery results are limited to the other psychosis group. Furthermore, reduced N400 and increased reaction times correlated with greater psychotic symptoms, worse global assessment of functioning scores, unemployment, and impaired social functioning. CONCLUSIONS: Abnormalities in the N400 are not specific to schizophrenia; in addition, the N400 may be a useful neural correlate of recovery and real-world functioning across psychotic disorders