Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: a PET study using [ 18 F]-VAT.

BACKGROUND: Despite longstanding interest in the central cholinergic system in schizophrenia, cholinergic imaging studies in patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography (PET) study using [18 F]-VAT, a new radiotracer which targets the vesicular acetylcholine transporter (VAChT) as a proxy measure of acetylcholine transmission capacity, in patients with schizophrenia, and explored relationships of VAChT with clinical symptoms and cognition.

METHODS: Eighteen adults with schizophrenia or schizoaffective disorder (SCZ) and 14 healthy controls underwent PET scan with [18 F]-VAT. Distribution volume (VT ) for [18 F]-VAT was derived for each region of interest (ROI) and group differences in VT were assessed with two-sample t-tests. Functional significance was explored through correlations between VT and scores on the Positive and Negative Syndrome Scale (PANSS) and a computerized neurocognitive battery (PennCNB).

RESULTS: No group differences in [18 F]-VAT VT were observed. However, within SCZ, psychosis symptom severity associated positively with VT in multiple ROIs, with strongest effects in hippocampus, thalamus, midbrain, cerebellum, and cortex. Also in SCZ, working memory performance was negatively associated with VT in substantia innominata and several cortical ROIs including dorsolateral prefrontal cortex.

CONCLUSION: In this initial study, severity of two important features of schizophrenia-psychosis and working memory deficit-were strongly associated with [18 F]-VAT VT in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in schizophrenia and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in schizophrenia and development of therapeutic targets.