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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 (V_T) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers.

Forty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [¹¹C]UCB-J positron emission tomography to index [¹¹C]UCB-J V_T 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 …