Schizophrenia and PET

Schizophrenia is a chronic, highly heritable, mental health condition associated with positive (psychotic), negative, and cognitive symptoms. Positive symptoms include delusions and hallucinations, negative symptoms include anhedonia and asociality, and cognitive symptoms include impaired working memory and executive function (McCutcheon et al., 2020).

Glucose utilisation is a marker of cerebral metabolism that can be studied with FDG PET. Reduction in FDG uptake have been found in the frontal lobe of the brain (Townsend et al., 2022).

Excess synaptic pruning is a major disease mechanism for schizophrenia. Synaptic vesicle glycoprotein 2A (SV2A) is considered as a marker of synaptic density in the brain. PET studies have shown reductions in cortical uptake of SV2A radioligands (Onwordi et al., 2020; Radhakrishnan et al., 2021). Reductions are evident already in early-course schizophrenia, and [¹¹C]UCB-J binding correlates positively with cognitive performance negatively with severity of delusions (Yoon et al., 2023).

Dopamine model of schizophrenia postulates that some symptoms are due to a functional excess of brain dopamine. D₂ receptor antagonists have antipsychotic properties, and treatment of schizophrenia has been based on D₂R blockade. Presynaptic dopamine synthesis and dopamine turnover, assessed using FDOPA PET, is higher in the striatum of patients with schizophrenia than in healthy controls (Cumming et al., 2021). Dopamine transporter (DAT) transports released dopamine back into presynaptic terminals. PET and SPECT studies of striatal DAT and D_2/3R availability in schizophrenia have led to variable results, and shown higher variability in patients than in healthy subjects (Brugger et al., 2020; Cumming et al., 2021). Thalamic D_2/3R availability is significantly lower in patients (Plavén-Sigray et al., 2022).

Serotonin receptor and transporter availability in schizophrenia has been studied with PET. Some studies have shown increases in receptor availability. Increases in serotonin transporter availability have not been observed, but there may be negative correlation between the severity of negative symptoms with SERT availability (Cumming et al., 2021

Opioid system μ opioid receptor (MOR) availability is decreased in schizophrenia (Ashok et al., 2019).

Histamine receptor binding of H₁R radioligand was regionally decreased in schizophrenia (Iwabuchi et al., 2005).

Neuroinflammation may be involved in schizophrenia, especially in the acute phase. Neuroinflammation has been studied with PET using TSPO radioligands (Meyer et al., 2021).

Histone deacetylase radioligand binding is reduced in schizophrenia in brain regions related to cognitive symptoms (Gilbert et al., 2019).

See also:

• Dopaminergic system
• Synaptic density

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Literature

Cumming P, Abi-Dargham A, Gründer G. Molecular imaging of schizophrenia: Neurochemical findings in a heterogeneous and evolving disorder. Behav Brain Res. 2021; 398: 113004. doi: 10.1016/j.bbr.2020.113004.

Hirvonen J, Hietala J. Dysfunctional brain networks and genetic risk for schizophrenia: specific neurotransmitter systems. CNS Neurosci Ther. 2011; 17(2): 89-96. doi: 10.1111/j.1755-5949.2010.00223.x.

Howes OD, Cummings C, Chapman GE, Shatalina E. Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes. Neuropsychopharmacology 2023; 48(1): 151-167. doi: 10.1038/s41386-022-01426-x.

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Updated at: 2023-08-02
Created at: 2023-01-19
Written by: Vesa Oikonen