Background: Diminished suppression of the P50 response, a consistent finding in schizophrenia, has also been reported in patients with psychotic bipolar disorder. It is a promising endophenotype for schizophrenia, but its relationship to genetic liability in bipolar disorder is unknown. We therefore assessed whether diminished P50 suppression is associated with familial risk for psychotic bipolar disorder.
Methods: The P50 response was collected in a conditioning (C)--testing (T) paradigm from 42 outpatients with bipolar 1 disorder who had experienced psychotic symptoms and 44 of their unaffected first-degree relatives, all from families multiply affected with bipolar disorder or another non-organic psychotic disorder; 48 healthy control subjects were also studied. The T/C ratio was compared between the groups, with linear regression analyses and robust variance estimators for clustered data.
Results: Both patients (estimated mean difference in T/C ratio to control subjects, 32, 95% confidence interval [CI] 15-48, p=.001) and unaffected relatives (20, 95% CI 7-32, p=.002) demonstrated higher T/C ratio, thus indicating diminished P50 suppression compared with control subjects.
Conclusions: To our knowledge, this is the first report of diminished P50 gating in unaffected relatives of psychotic bipolar disorder patients from multiply affected families. Our results suggest that impaired P50 gating is a putative endophenotype for psychotic bipolar disorder and thus might reflect the impact of susceptibility genes across psychosis.