Imaging-based neurochemistry in schizophrenia: a systematic review and implications for dysfunctional long-term potentiation

Abstract

Cognitive deficits are commonly observed in patients with schizophrenia. Converging lines of evidence suggest that these deficits are associated with impaired long-term potentiation (LTP). In our systematic review, this hypothesis is evaluated using neuroimaging literature focused on proton magnetic resonance spectroscopy, positron emission tomography, and single-photon emission computed tomography. The review provides evidence for abnormal dopaminergic, GABAergic, and glutamatergic neurotransmission in antipsychotic-naive/free patients with schizophrenia compared with healthy controls. The review concludes with a model illustrating how these abnormalities could lead to impaired LTP in patients with schizophrenia and consequently cognitive deficits.

Keywords: GABA; MRS; PET; SPECT; dopamine; glutamate; long-term potentiation; schizophrenia.

Fig. 1.

Hypoactive NMDA receptor causes downstream hyperglutamatergic activity, which leads to the conversion of glutamate to glutamine by the enzyme glutaminase, as such increasing glutamine levels. Glutamine is a molecule which cannot exert neurotoxic effects. To balance out excitatory activity with inhibitory activity, glutamate is converted into GABA, the main inhibitory neurotransmitter. Extracellular dopamine is regulated by NMDA receptors located on the dopaminergic neuron. Hypoactive NMDA receptors on cortico-brainstem pathway reduce inhibition of tonic dopamine neurons of the mesocortical pathway, which leads to increase in DA release.^, To attenuate the dopamine release, D_2/3 receptor density is upregulated.

Fig. 2.

Neurochemicals and receptors in patients with schizophrenia relative to healthy controls in different brain regions. *Evidence is based on one study.