Neurochemical brain imaging investigations of schizophrenia

Neurochemical brain imaging methods developed over the past 20 years offer significant promise for elucidating the biochemical underpinnings of schizophrenia. The two general methodologies used for these studies have been: 1) radiotracer imaging: PET (positron emission tomography) and SPECT (single photon emission computed tomography); and 2) NMR (nuclear magnetic resonance) imaging: fMRI (functional magnetic resonance imaging) and MRS (magnetic resonance spectroscopy). Despite conflicting findings, striatal D2 receptor density may be elevated in some, but not all patients. Elevated synthesis, and increased release of dopamine after amphetamine challenge have also been reported. Imaging of cortical 5-HT2A receptors suggests that this system is unaffected, in conflict with findings of postmortem studies. Although prior postmortem studies suggested an increase in cortical GABAA receptors, three SPECT studies have found no significant changes. MRS studies have shown decreased levels of NAA (N-acetyl-aspartate) moieties in hippocampus and frontal cortex of schizophrenic patients, which is consistent with the reported loss of neurons and neuropil in postmortem brains. In conclusion, developments in radiotracer and NMR imaging have provided promising leads to the biochemical abnormalities associated with schizophrenia. Future significant understanding is likely to occur with the development of new probes and enhanced instrument technology, when applied with an appreciation of the heterogeneity of the disorder and the need for careful clinical assessment of patients.