Genetic load on amygdala hypofunction during sadness in nonaffected brothers of schizophrenia patients

Objective: In a previous study, the authors reported that patients with schizophrenia show subcortical-limbic hypoactivity during sadness. In this study, they capitalized on those findings in order to assess the genetic influence of negative mood experience in schizophrenia patients. Brain activity was measured during mood induction in patients with schizophrenia and their first-degree nonaffected relatives. Method: Functional magnetic resonance imaging was used to investigate 13 male patients with schizophrenia, their nonaffected brothers (N=13), and a group of 26 individually matched healthy subjects unrelated to the siblings during induction of sad and happy moods as well as during a cognitive control task. A regional analysis was applied to investigate a possible subcortical-limbic dysfunction in relatives. Results: Mood induction was successful in all groups according to subjective ratings. During sadness induction, the patients and their nonaffected siblings demonstrated less activity in the amygdala compared with the healthy group of nonrelatives. Other regions of interest, such as the left orbitofrontal cortex, the left superior temporal cortex, and the left precuneus/posterior cingulate revealed significant group differences only between patients and nonrelated healthy subjects. During positive mood induction, no group differences could be found in the amygdala. Conclusions: Following induction of sad mood, both patients with schizophrenia and their nonaffected brothers displayed reduced brain activity in the amygdala. Such hypoactivity is likely to represent a genetic influence and indicates that efficient compensatory mechanisms capable of preventing the onset of the illness must exist in nonaffected relatives.