Effectiveness of Cerebellar Circuitry Modulation in Schizophrenia: A Systematic Review

Abstract

Structural and functional abnormalities of the cerebellum have been observed in schizophrenia since the first neuroimaging studies. More recently, the functions of the cerebellum have been extended beyond sensorimotor control to include participation in higher-level cognition and affective regulation. Consistently, the "cognitive dysmetria" theory posits that dysfunctions of cortical-subcortical-cerebellar circuitry may be crucial for the pathogenesis of different clinical features of schizophrenia. This conceptual framework offers a set of testable hypotheses, now that various tools to exert direct modulation of cerebellar activity are available. We conducted a systematic review of studies examining the effects of cerebellar modulation in schizophrenia. Two independent authors conducted a search within PubMed for articles published up to April 2019 and identified 10 studies (three randomized controlled trials, two open-label studies, two case reports, one preclinical study) describing the effects of cerebellar circuitry modulation in patients with schizophrenia or animal models. The majority of interventions were uncontrolled and used stimulation of the cerebellar vermis, using transcranial magnetic stimulation or transcranial direct-current stimulation. Most studies detected improvements after cerebellar modulation. Clinical changes mostly pertained the domains of negative symptoms, depressive symptoms and cognitive functions. In conclusion, few studies examined the effects of cerebellar modulation in schizophrenia but yielded promising results. This approach may hold therapeutic potential, pending further methodologically robust replication.