Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [18F]-VAT.

Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [18F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [18F]-VAT. Distribution volume (V T) for [18F]-VAT was derived for each region of interest, and group differences in V T were assessed with 2-sample t tests. Functional significance was explored through correlations between V T and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). No group differences in [18F]-VAT V T were observed. However, within the SCZ group, psychosis symptom severity was positively associated with V T in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with V T in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. In this initial study, the severity of 2 important features of SCZ—psychosis and working memory deficit—was strongly associated with [18F]-VAT V T in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets. [ABSTRACT FROM AUTHOR]