Severity of bipolar disorder is associated with impairment of response inhibition

Background: Pathological impulsivity in bipolar disorder could be related to deficiencies in mechanisms involved in attention or response inhibition. We investigated these mechanisms in subjects with bipolar disorder and examined relationships to severity of course of illness, use of medication, affective state, age, education, and gender. We measured two complementary aspects of response inhibition: attention-based and reward-based. Methods: Subjects with bipolar disorder (n = 112) and healthy controls (n = 71) were recruited from the community. Diagnoses were rendered using the SCID for DSMIV. Impulsivity-related measures included the Immediate Memory Task (IMT), a form of the Continuous Performance Task, and the Single Key Impulsivity Paradigm (SKIP), an operant procedure measuring ability to delay responding for a reward. Results: Subjects with bipolar disorder had fewer correct detections (Effect Size (ES) = 0.5), prolonged reaction times (ES = 0.88), and decreased discriminability (ES = 0.57) on the IMT compared to controls. History of frequent episodes, substance use disorders, or suicide attempts predicted faster reaction times, especially to a commission error. Subjects with bipolar disorder who also met criteria for an Axis II disorder had fewer correct detections, more commission errors relative to correct detections, and poorer discriminability on the IMT than other subjects with bipolar disorder. Subjects with bipolar disorder made more responses on the SKIP than did controls (ES = 0.5), with a shorter maximum delay (ES = 0.62), consistent with inability to delay reward. Probit analysis showed that faster reaction time to a commission error on the IMT was associated with history of substance use disorder, suicide attempt, or many previous episodes. Effects of medication or affective state did not account for these differences. Discussion: Bipolar disorder was associated with impairment in attention and response inhibition, encompassing impaired inhibition of rapid responses and an inability to delay reward, and resulting in impulsivity. Response inhibition mechanisms are impaired further in subjects with more severe complications of illness. (C) 2008 Elsevier B.V. All rights reserved.