ABSTRACT
The social defeat (SD) hypothesis of schizophrenia posits that repeated experiences of SD may lead to sensitization of the mesolimbic dopaminergic system and to precipitation of psychosis. Based on previous definitions adapted to a human experimental paradigm, we prepared a computer simulation of SD to mimic this subjective experience. We measured prefrontal cortex (PFC) activity in subjects with schizophrenia and healthy controls during exposure to a single SD experience with functional near infrared spectroscopy. PFC activity declined in both groups. Compared with the control condition, SD exposure was associated with a broader decline in left ventromedial, right medial and right lateral PFC activity in healthy controls (n=25), and a sharper decline in right ventrolateral PFC activity in subjects with schizophrenia (n=25). The activity in the right ventrolateral PFC, was significantly lower in patients compared with controls. This may be due to a deficiency in emotion regulation or self-control, or it may be related to impaired empathy in schizophrenia. Different patterns of brain activity during the SD experience in subjects with schizophrenia versus healthy controls may provide indirect evidence regarding the SD hypothesis of schizophrenia.