Dopaminergic basis of the psychosis-prone personality investigated with functional magnetic resonance imaging of procedural learning

Abstract

Previous evidence shows a reliable association between psychosis-prone (especially schizotypal) personality traits and performance on dopamine (DA)-sensitive tasks (e.g., prepulse inhibition and antisaccade). Here, we used blood oxygen level-dependent (BOLD) fMRI and an established procedural learning (PL) task to examine the dopaminergic basis of two aspects of psychosis-proneness (specific schizotypy and general psychoticism). Thirty healthy participants (final N = 26) underwent fMRI during a blocked, periodic sequence-learning task which, in previous studies, has been shown to reveal impaired performance in schizophrenia patients given drugs blocking the DA D2 receptor subtype (DRD2), and to correspond with manipulation of DA activity and elicit fronto-striatal-cerebellar activity in healthy people. Psychosis-proneness was indexed by the Psychoticism (P) scale of the Eysenck Personality Questionnaire-Revised (EPQ-R; 1991) and the Schizotypal Personality Scale (STA; 1984). EPQ-R Extraversion and Neuroticism scores were also examined to establish discriminant validity. We found a positive correlation between the two psychosis-proneness measures (r = 0.43), and a robust and unique positive association between EPQ-R P and BOLD signal in the putamen, caudate, thalamus, insula, and frontal regions. STA schizotypy score correlated positively with activity in the right middle temporal gyrus. As DA is a key transmitter in the basal ganglia, and the thalamus contains the highest levels of DRD2 receptors of all extrastriatal regions, our results support a dopaminergic basis of psychosis-proneness as measured by the EPQ-R Psychoticism.

Keywords: dopamine; schizotypy; sequence learning; striatum; thalamus.

Figure 1

Illustration of pattern trials (taken from Kumari et al., 2002).

Figure 2

Mean reaction times (+1 SEM) to random and pattern trials over the five blocks.

Figure 3

Relationship between schizotypy and PL scores. PL is calculated as the difference in reaction time between blocks of random trials and blocks of pattern trials. The schizotypy score are derived from the STA.

Figure 4

Activation across all participants during pattern, relative to random, trials. Images are left-right reversed.

Figure 5

Brain activity positively correlated with the EPQ-R Psychoticism (P) scores. Images are left-right reversed.

Figure 6

Brain activity positively correlated with the STA schizotypy scores. Images are left-right reversed.