Whole brain grey matter synaptic terminal density, age and intellectual functioning in schizophrenia: an in vivo [11C]UCB-J positron emission tomography study

Converging lines of evidence implicate synaptic loss in cognitive impairment associated with schizophrenia. However, it remains unknown whether synaptic terminal density and premorbid intellectual functioning are related in vivo, or whether there are age-related changes in them in schizophrenia. To address this, we investigated whole brain grey matter synaptic vesicle glycoprotein 2A (SV2A) levels and examined their relationship with intellectual functioning and age, in forty-three patients with schizophrenia (SCZ) and 26 healthy volunteers (HV), using [¹¹C]UCB-J positron emission tomography (PET). Whole brain grey matter [¹¹C]UCB-J distribution volume ratio (DVR) was significantly lower in the SCZ than the HV group (Cohen's d = 0.64, p = 0.01), and negatively correlated with age in both groups (Spearman's rho = -0.46 to -0.55), with no significant group difference in magnitude of DVR-age correlations (z = 0.44, p = 0.66). Current (Cohen's d = 0.73) and premorbid IQ (Cliff's delta = 0.37) were significantly lower in the SCZ than the HV group, though DVR was not significantly associated with current or premorbid IQ in either group (including in chronic medicated and early-course unmedicated SCZ subgroups). The group differences in DVR are consistent with a global deficit in synaptic terminal density in schizophrenia, with similar age-related changes in people with schizophrenia and healthy volunteers. The lack of significant relationships between DVR and premorbid or current cognitive measures are not consistent with the hypothesis that lower levels of synaptic terminal density observed in schizophrenia underlie lower levels of intellectual functioning in the disorder.