Citalopram enhances action inhibition systems in Parkinson's disease

Abstract

Impulsivity in Parkinson’s disease (PD) is highlighted by the severity of impulse control disorders (ICDs). However, subtler impulsivity is common even in the absence of ICDs and is likely to be multifactorial. In addition to dopaminergic ‘overdose’1,2 and structural changes3 in the frontostriatal circuits for motor control, we propose that changes in serotonergic projections to the forebrain also exacerbate the impairment of response inhibition. Enhancing central serotonin transmission with selective serotonin reuptake inhibitors (SSRIs) might therefore provide adjunctive treatment for behavioural impulsivity in Parkinson’s disease. We investigated whether the SSRI citalopram reduces impulsivity and enhances the neural systems mediating response inhibition in Parkinson’s disease. We studied two forms of inhibition: (1) restraint, using NoGo events; and (2) cancellation, in terms of the Stop-Signal Reaction Time (SSRT). There is strong preclinical evidence from animal and human studies that serotonin plays an important role in regulating action restraint4. In contrast, the link between serotonin and action cancellation is less well established. We tested three specific hypotheses. Hypothesis1: PD impairs both action restraint and cancellation. Hypothesis2: The effect of citalopram on behavioural performance depends on patients’ disease severity. Hypothesis3: The behavioural effect relates to the enhancement of inferior frontal cortical activation following citalopram.