Investigation of Risperidone Treatment Associated With Enhanced Brain Activity in Patients Who Stutter

Abstract

Stuttering is a childhood onset fluency disorder that leads to impairment in speech. A randomized, double-blinded placebo-controlled study was conducted with 10 adult subjects to observe the effects of risperidone (a dopamine receptor 2/serotonin receptor 2 antagonist) on brain metabolism, using [18F] deoxyglucose as the marker. At baseline and after 6 weeks of taking risperidone (0.5–2.0 mg/day) or a placebo pill, participants were assigned to a solo reading aloud task for 30 min and subsequently underwent a 90-min positron emission tomography scan. Paired t-tests were performed to compare the pre-treatment vs. post-treatment in groups. After imaging and analysis, the blind was broken, which revealed an equal number of subjects of those on risperidone and those on placebo. There were no significant differences in the baseline scans taken before medication randomization. However, scans taken after active treatment demonstrated higher glucose uptake in the specific regions of the brain for those in the risperidone treatment group (p < 0.05). Risperidone treatment was associated with increased metabolism in the left striatum, which consists of the caudate and putamen, and the Broca’s area. The current study strengthens previous research that suggests the role of elevated dopamine activity and striatal hypometabolism in stuttering. We propose that the mechanism of risperidone’s action in stuttering, in part, involves increased metabolism of striatal astrocytes. We conclude that using neuroimaging techniques to visualize changes in the brain of those who stutter can provide valuable insights into the pathophysiology of the disorder and guide the development of future interventions.

Stuttering: A Disorder of Energy Supply to Neurons?

“…Recently, Maguire et al ( 2021 ) discussed this possible interaction between dopamine and metabolism, with astrocytes as a mediating link. It has been shown that astrocytes carry both D1 and D2 receptors, and that pharmacological blockade of the D2 receptors increases the metabolic activity of astrocytes in rats (Konopaske et al, 2013 ).…”

“…It has been shown that astrocytes carry both D1 and D2 receptors, and that pharmacological blockade of the D2 receptors increases the metabolic activity of astrocytes in rats (Konopaske et al, 2013 ). The study by Maguire et al ( 2021 ), of persons who stutter, reported that the D2 antagonist risperidone resulted in increased uptake of glucose during speech, in the left striatum and in the Broca’s area. The stuttering was reduced in the risperidone-group, compared to the placebo group.…”

Morphometric analysis of astrocytes in vocal production circuits of common marmoset (Callithrix jacchus)

“…In accordance with this hypothesis, it was suggested that a defect in astrocytes can lead to developmental stuttering (a common speech disorder that affects the fluency of speech) (Han et al, 2019;Maguire et al, 2021). Thus, it will be imperative to further understand the role of astrocytes in circuits that are involved in control of vocal production.…”

Phenome risk classification enables phenotypic imputation and gene discovery in developmental stuttering

“… 14 The roles of these astrocytes in the onset of stuttering are not well characterized; however, recent studies have contributed to a growing body of evidence that dopamine receptor D2 blockers can impact stuttering behavior, perhaps because of increased astrocyte metabolism in the striatum. 15 These studies suggest that dopamine projection from the basal ganglia might contribute to disturbances in speech and vocalization, and the findings potentially support pharmacological means for treatment. 16 , 17 Recent evidence also implicates autoimmune reactions from group A beta-hemolytic streptococcus (GAS [MIM: 607395 ]) infections that target specific cell types within the basal ganglia as a potential cause of stuttering.…”