Changes in responses of the amygdala and hippocampus during fear conditioning are associated with persecutory beliefs

Abstract

Abstract The persecutory delusion represents the most common symptom of psychosis, yet its underlying neurobiological mechanisms are poorly understood. Prior studies have suggested that abnormalities in medial temporal lobe-dependent associative learning may contribute to this symptom, leading to diminished “safety signaling.” In the current study, this hypothesis was tested in a non-clinical sample of young adults without histories of psychiatric treatment (n = 64), who participated in a classical Pavlovian fear conditioning paradigm while fMRI data were collected. During the fear conditioning procedure, participants viewed face stimuli which were paired (the CS+) or not paired (the CS-) with an aversive stimulus (a mild electrical shock). Fear conditioning-related neural responses were measured in two medial temporal lobe regions, the amygdala and hippocampus, and in other closely connected brain regions of the salience and default networks. The participants without persecutory beliefs (n = 43) showed greater responses to the CS- compared to the CS+ in the right amygdala and hippocampus (a “safety signal”), while the participants with persecutory beliefs (n = 21) failed to exhibit this response (ps > .05). These between-group differences were not accounted for by symptoms of depression, anxiety or the psychosis prodrome. However, the severity of subclinical psychotic symptoms overall was correlated with the level of this aberrant response in the amygdala (p = .013) and hippocampus (p = .033). Thus, these findings provide evidence for a disruption of medial temporal lobe-dependent associative learning in subclinical psychotic symptoms, specifically persecutory thinking.