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

Background: 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 [F]-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.

Methods: 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 [F]-VAT. Distribution volume (V) for [F]-VAT was derived for each region of interest, and group differences in V were assessed with 2-sample t tests. Functional significance was explored through correlations between V and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB).

Results: No group differences in [F]-VAT V were observed. However, within the SCZ group, psychosis symptom severity was positively associated with V 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 in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex.

Conclusions: In this initial study, the severity of 2 important features of SCZ-psychosis and working memory deficit-was strongly associated with [F]-VAT V 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.