Abnormal Modulation of Amygdala Activity in Schizophrenia in Response to Direct- and Averted-Gaze Threat-Related Facial Expressions

Abstract

Reduced amygdala activation in individuals with schizophrenia is thought to contribute to impairments in emotion recognition and social functioning. Recent work, however, suggests that amygdala abnormalities in schizophrenia are more nuanced than generalized hypoactivation and that modulation of amygdala responses across different stimulus types may be more closely related to social functioning than to overall levels of amygdala activation during a task. The authors investigated amygdala modulation during emotion recognition in patients by manipulating the gaze direction of threat-related expressions. Blood-oxygen-level-dependent functional MRI was used to measure neural activation in 37 healthy volunteers and 35 schizophrenia patients while participants identified the emotion (anger or fear) displayed on facial stimuli that appeared with either direct or averted gaze. Analysis of percent signal change in the amygdala bilaterally revealed a three-way interaction of emotion, gaze, and group, demonstrating significantly reduced amygdala responses to direct-gaze anger expressions in the patient group but comparable levels of activation across groups in all other conditions. Within the patient group, amygdala responses to direct-gaze anger expressions were positively correlated with level of functioning. These findings extend previous reports of amygdala hypoactivation in schizophrenia by identifying abnormal amygdala modulation in response to varying emotional stimuli. Additionally, the strong relationship between amygdala activation and social and occupational functioning underscores the need for investigations of amygdala modulation in schizophrenia that further specify the nature of these impairments and that examine a potential causal link between amygdala activation and functioning.