Limbic Activation Associated With Misidentification of Fearful Faces and Flat Affect in Schizophrenia

CONTEXT: Deficits in emotion processing are prominent in schizophrenia, and flat affect is resistant to treatment and portends poor outcome. Investigation of the underlying neural circuitry can elucidate affective dysfunction. OBJECTIVE: To examine the brain circuitry for facial emotion processing, dissecting response to task demands from effects of the appearance of facial expressions. DESIGN: A facial emotion identification task was presented during high-field (4-T) magnetic resonance imaging. Blood oxygenation level-dependent changes were contrasted for task compared with a scrambled face baseline (blocked analysis) and for the appearance of each of the following 4 target expressions compared with neutral faces (event related): happy, sad, anger, and fear. SETTING: Participants from the Schizophrenia Research Center underwent a functional magnetic resonance imaging study at the University of Pennsylvania Medical Center. PARTICIPANTS: Patients with DSM-IV-defined schizophrenia (n = 16) and healthy controls (n = 17) were recruited from the community. MAIN OUTCOME MEASURES: The percentage of signal change for each contrast and performance and clinical symptom severity ratings. RESULTS: Patients showed reduced limbic activation compared with controls for the emotion identification task. However, event-related analysis revealed that whereas in controls greater amygdala activation was associated with correct identifications of threat-related (anger and fear) expressions, patients showed the opposite effect of greater limbic activation, portending misidentifications. Furthermore, greater amygdala activation to the presentation of fearful faces was highly correlated with greater severity of flat affect. CONCLUSIONS: Abnormal amygdala activation in schizophrenia in response to presentation of fearful faces is paradoxically associated with failure to recognize the emotion and with more severe flat affect. This finding suggests that flat affect in schizophrenia relates to overstimulation of the limbic system.