Table 3 Summary of imaging findings in schizophrenia and people at risk for schizophrenia, from the literature discussed in this review, and key considerations for understanding if there are synaptic density changes in the disorder.*
From: Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes
Modality and measure | Main findings in genetically (GHR) and clinically high risk (CHR) | Main findings in first episode psychosis (FEP) | Main findings in chronic schizophrenia | Longitudinal findings | Effects of antipsychotic medication | Limitations |
|---|---|---|---|---|---|---|
Structural MRI: gyrification index | No meta-analysis: studies generally support ↑ | No meta-analysis: studies generally support ↑ | Meta-analysis shows ↓ globally (systematic review generally supports this, especially in older patients) | No meta-analysis: some studies show faster rate of decrease in schizophrenia | No meta-analysis: limited indirect evidence for widespread ↓ from longitudinal studies | Limited number of studies, particularly in early illness and of longitudinal change. No studies yet link GI to synaptic markers |
Structural MRI: cortical grey matter (GM) volume | GHR: ↓ thalamus ↑ ventricles ↔ accumbens ↔ amygdala ↔ hippocampus ↔ pallidum ↔ putamen CHR (who transition to psychosis relative to those who do not transition): ↓ anterior cingulate ↓ superior temporal gyrus | ↓ amygdala ↓ anterior cingulate ↓ frontal lobe ↓ hippocampus ↓ thalamus ↓ temporal lobe ↑ ventricles ↔ caudate ↔ putamen | ↓ frontal lobe ↓ fusiform ↓ hippocampus ↓ insula (L) ↓ prefrontal lobe ↓ superior temporal gyrus ↓ temporal lobe ↓ total brain volume ↑ ventricles | Greater volume loss of: total cortical GM, superior temporal gyrus, Heschl gyrus (L), planum temporale (L), frontal cortex, temporal cortex, thalamus, caudate nucleus, insula, periventricular area, putamen, cingulate cortices Rate of GM volume loss most pronounced early in illness | Drug free patients: ↓ fusiform gyrus (L) ↓ inferior frontal gyrus (L) ↓ superior temporal gyrus (R) ↓ supramarginal gyrus (L) ↑ lingual gyrus (R) ↑ superior frontal gyrus (R) ↑ progressive cortical GM volume loss associated with ↑ daily antipsychotic intake in patients taking at least one first-generation APD vs. those taking second-generation only | Not specific to synapses, and could include differences in glia, neuronal soma volumes, dendrites and other structural components |
Structural MRI: cortical grey matter density | n/a | n/a | ↓ insular cortex (bilateral) ↓ anterior cingulate ↓ parahippocampal gyrus (L) ↓ middle frontal gyrus ↓ postcentral gyrus ↓ thalamus ↑ putamen ↑ caudate (R) | n/a | n/a | Not specific to synapses, and could include difference in glia, neuronal soma volumes, dendrites and other components |
Structural MRI: cortical thickness | n/a | n/a | ↓ hemispheric cortical thickness bilaterally ↓ fusiform (bilateral) ↓ superior, middle and inferior temporal gyri (bilateral) ↓ superior frontal gyrus (L) ↓ pars opercularis (R) ↓ insula (bilateral) | Stronger negative correlation between increasing age and bilateral temporal pole thickness in schizophrenia than in controls | ↓ frontal lobe ↓ parietal lobe ↓ temporal lobe ↓ insula ↓ isthmus of cingulate gyrus (in medicated vs unmedicated and vs controls) | Not specific to synapses, and could include difference in glia, neuronal soma volumes, dendrites and other components |
Neurite orientation dispersion and density imaging | n/a | ↔ hippocampus n/a for other ROIs | ↓ temporal pole ↓ anterior hippocampal gyrus ↓ hippocampus | n/a | n/a | Not specific to synapses and could include differences in myelination of axons |
FDG PET: glucose utilisation | n/a | ↓ frontal cortex in chronic schizophrenia vs. FEP ↔ frontal cortex in FEP vs. controls | ↓ frontal cortex | n/a | ↓ frontal cortex in medicated/mixed patient vs. drug-naïve/drug-free patient cohorts | Changes in FDG uptake may represent changes in neuronal activity (not density) Significant FDG uptake by non-neuronal cells |
MRS studies of N-acetylaspartate (NAA) levels | ↓ hippocampus | ↓ frontal cortex ↓ anterior cingulate ↓ thalamus | ↓ hippocampus ↓ frontal cortex ↓ temporal cortex ↓ parietal cortex | n/a | In unmedicated FEP: ↓ frontal lobe ↓ anterior cingulate cortex ↓ dorsolateral prefrontal region ↓ frontal white matter ↓ thalamus | Expression of NAA is not specific to synapses |
[11 C]UCB-J PET: Synaptic Vesticle Protein 2 A (SV2A) levels | n/a | n/a | ↓ frontal lobe ↓ anterior cingulate ↓ hippocampus and potentially some other cortical regions | n/a | n/a | Does not measure postsynaptic elements |
