Behavioral response inhibition in psychotic disorders: diagnostic specificity, familiality and relation to generalized cognitive deficit

Abstract

Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n=523), their available first-degree biological relatives (n=656), and healthy participants (n=223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors.

Keywords: Family study; Psychotic bipolar disorder; Response inhibition; Schizophrenia; Stop signal.

Figure 1

Stop Signal task parameters. In Go trials, participants pressed the corresponding left or right button when a green circle appeared to the right or left of center. During Stop trials, they were to refrain from pushing the buttons. When participants did not respond within 650 ms on Go trials, a red ‘X’ and the word ‘faster’ were presented for 2500ms indicating that the participant failed a trial. On Stop trials in which the participants pressed a button, a red ‘X’ appeared over the stop sign to provide performance feedback indicating the failure to inhibit a response.

Figure 2

Nonlinear mixed model curves for patient groups and healthy participants, without the inclusion of the BACS covariate. Values for Stop Signal Delay on the X axis represent median Stop Signal delays for each of 14 time bins.

Figure 3

Nonlinear mixed model curves for relative groups and healthy participants, without the inclusion of the BACS covariate. Values for Stop Signal Delay on the X axis represent median Stop Signal delays for each of 14 time bins.

Figure 4

Comparison of standardized relative deficit (Hedges' g) in parameter b₁ (the Stop Signal Delay yielding a 50% error rate) in the SST (left plot) versus general cognitive deficit as measured by the BACS (right plot). All patient groups show significant deficit relative to healthy participants for both SST parameter b₁ and BACS, but while SST b₁ does not differ across patient groups, BACS deficits decrease across the spectrum of nonaffective and affective psychotic disorders from SZ to BPP.

Figure 5

Strategic slowing. Slowing of Go trial latencies by group, showing that all patient groups had significantly less strategic slowing during the SST relative to the baseline Go task than did healthy participants. HP: Healthy; SZ: Schizophrenia; SZA-D: Schizoaffective depressed type; SZA-BP: Schizoaffective bipolar type; BPP: Bipolar psychosis, * p<.05. all differences from BPP, ** p<.01, all differences from healthy participants