Relationship between synaptic density and cortical (micro)structure in healthy subjects, patients with schizophrenia spectrum disorder and unaffected siblings: a multimodal [11C]UCB-J PET and MRI study.

BACKGROUND: The structure and tissue composition of the cortex may be sensitive to loss of synapses. However, the relation between measurements of synaptic density, cortical thickness and microstructure remains unknown. These measures are reduced in schizophrenia spectrum disorders (SSD) and to a lesser degree in unaffected relatives. Here, we investigated if synaptic density and cortical (micro)structure are related in healthy subjects, and if these associations are altered in patients with SSD and unaffected siblings.

METHODS: Brain uptake of the tracer [ 11C]UCB-J, measured in-vivo with positron emission tomography (PET) was used as a proxy measure for synaptic density. Healthy subjects (n=25), patients with SSD (n=24) and unaffected siblings (n=25) underwent [ 11C]UCB-J PET, T1-weighted MRI and diffusion weighted imaging scans.

RESULTS: We found a positive relation between [ 11C]UCB-J BP ND and cortical thickness (β=0.61, p=.02) and showed a similar (yet non-significant) positive relation in unaffected siblings (β=0.41, p=.09). This relation was not present in patients with SSD (β=0.03, p=.90). Additionally, [ 11C]UCB-J BP ND had a negative relation with mean diffusivity (MD) in controls (β=-0.54, p=.01) and unaffected siblings (β=-0.47, p=.01). In patients with SSD, again, this relation was disrupted (β=0.07, p=.78).

CONCLUSION: We found a robust association between synaptic density and cortical (micro)structure in healthy individuals. The lost relation in patients suggest that SSD-related synapse loss is not proportional to the number and organization of grey matter constituents. Despite the shared genetic risk, unaffected siblings preserve this relation, suggesting absence of a second hit inducing excessive synaptic pruning.