BACKGROUND: The synaptic hypothesis is an influential theory of the pathoaetiology of schizophrenia. Supporting this, there is lower uptake of the synaptic terminal density marker UCB-J in patients with chronic schizophrenia compared to controls. 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 schizophrenia (SCZ) recruited from first-episode services compared to healthy volunteers (HV). METHODS: Forty-two volunteers (SCZ n = 21, HV n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio (DVR) in the anterior cingulate, frontal, and dorsolateral prefrontal cortices, temporal, parietal and occipital lobes, hippocampus, thalamus and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale (PANSS). RESULTS: We found no significant effects of group on [11C]UCB-J VT or DVR in most regions of interest (effect sizes from d=0.0 to 0.7, p>0.05), other than lower DVR in the temporal lobe (d=0.7, uncorrected p<0.05) and lower VT/fp in the anterior cingulate cortex in patients (d=0.7, uncorrected p<0.05). PANSS total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r =-0.48, p=0.03). CONCLUSIONS: These findings indicate that large differences in synaptic terminal density are not present early in schizophrenia, although there may be more subtle effects. When taken with prior evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of schizophrenia.