Subcortical modulation of attentional control by second-generation antipsychotics in first-episode psychosis

Abstract

Psychotic disorders are characterized by significant deficits in attentional control, but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood. Moreover, little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy. In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic (risperidone or aripiprazole) in a double blind randomized clinical trial and then again following approximately 12 weeks of treatment. In addition, 14 age-, and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks. Patients showed significantly greater activation than healthy volunteers in the right globus pallidus, left thalamus, and right thalamus at the time of the baseline scan. Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent (BOLD) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance. No changes in globus pallidus activation were observed in healthy volunteers over this time period. These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness. These findings have implications for understanding how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics.

Keywords: Attentional control; Basal ganglia; First episode psychosis; Functional magnetic resonance imaging; Schizophrenia; Second generation antipsychotics.

Figure 1

Accuracy and Reaction Time (with standard error bars) in Patients and Healthy Volunteers at Baseline and 12 Week Followup Timepoints Note: Asterisks denote the following: blue = significant change in controls, red = significant increase in patients, black = significant difference between patients and controls at 12 week scan).

Figure 2

Baseline activation at Z = 0 slice; (A) Red/Yellow: patients higher than healthy volunteers; Blue: patients lower than healthy volunteers; (B) Right Globus Pallidus ROI; (C) Right Thalamus; (D) Left Thalamus

Figure 2

Baseline activation at Z = 0 slice; (A) Red/Yellow: patients higher than healthy volunteers; Blue: patients lower than healthy volunteers; (B) Right Globus Pallidus ROI; (C) Right Thalamus; (D) Left Thalamus

Figure 3

Regions demonstrating Significant Changes in BOLD Activation in Patients and Healthy Volunteers

Figure 4

(A) Contrast Z score in the Right Globus Pallidus. (B) Association between baseline to 12 week change in the BPRS Thought Disturbance factor (where negative values indicate improvement) and baseline to 12 week change in contrast Z score (where negative values indicate reduced activation) in the Right Globus Pallidus. (C) Association between baseline to 12 week improvement in the BPRS Unusual Thought Content item and baseline to 12 week change in contrast Z score in the Right Globus Pallidus. (D) Association between baseline to 12 week change in the BPRS Thought Disturbance factor and baseline to 12 week change in response accuracy in the Interference condition.

Figure 4

(A) Contrast Z score in the Right Globus Pallidus. (B) Association between baseline to 12 week change in the BPRS Thought Disturbance factor (where negative values indicate improvement) and baseline to 12 week change in contrast Z score (where negative values indicate reduced activation) in the Right Globus Pallidus. (C) Association between baseline to 12 week improvement in the BPRS Unusual Thought Content item and baseline to 12 week change in contrast Z score in the Right Globus Pallidus. (D) Association between baseline to 12 week change in the BPRS Thought Disturbance factor and baseline to 12 week change in response accuracy in the Interference condition.