An MRI study of midbrain morphology in patients with schizophrenia: Relationship to psychosis, neuroleptics, and cerebellar neural circuitry

Background: The midbrain contains the perikarya of all the dopamine neurons in the human brain. Although other neurochemicals may well be involved, do pamine dysregulation is central in the pathophysiology of psychosis. Despit e this, few imaging studies have evaluated the morphology of the midbrain. Methods: Using high-resolution magnetic resonance imaging, morphology of th ree posterior fossa and brain stem structures were measured: midbrain, pens , and medulla. The patient sample consisted of 50 men with schizophrenia, m atched by gender and age to 50 healthy control subjects. Results: Patients had significantly smaller midbrain measures compared with control subjects, there were no differences between groups in measures of pons or medulla. Furthermore, midbrain size was significantly and inversely correlated with positive symptoms and cumulative neurolept ic exposure, bu t not with negative or disorganized symptoms. After controlling for the eff ect of cumulative neuroleptic exposure, the relationship between midbrain m orphology and positive symptoms remained significant. Conclusions: Midbrain morphology of patients with schizophrenia is abnormal , being smaller in patients compared with control subjects. Although this a ppears to be specifically related to psychotic symptoms, there is also a ro bust medication effect, with greater exposure to neuroleptics being associa ted with greater morphologic abnormality. We discuss the role of dopaminerg ic dysregulation and possible neural circuit involvement. Biol Psychiatry 2 001;49:13-19 (C) 2001 Society of Biological Psychiatry.