Background: The synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [11C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers. Methods: Forty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio in the anterior cingulate, frontal, and dorsolateral prefrontal cortices; the temporal, parietal and occipital lobes; and the hippocampus, thalamus, and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale. Results: We found no significant effects of group on [11C]UCB-J VT or distribution volume ratio in most regions of interest (effect sizes from d = 0.0–0.7, p >.05), with two exceptions: we found lower distribution volume ratio in the temporal lobe (d = 0.7, uncorrected p <.05) and lower VT/fp in the anterior cingulate cortex in patients (d = 0.7, uncorrected p <.05). The Positive and Negative Syndrome Scale total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r = −0.48, p =.03). Conclusions: These findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects. When taken together with previous evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of SCZ.

Original languageEnglish
Pages (from-to)639-646
Number of pages8
JournalBiological psychiatry
Issue number7
Publication statusPublished - 1 Apr 2024


  • Antipsychotic-free
  • Positron emission tomography
  • Schizophrenia
  • SV2A
  • Synaptic density
  • UCB-J


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