Article Text

Download PDFPDF

The ever increasing complexity of schizophrenia

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Is schizophrenia a syndrome, its symptoms caused by different pathological abnormalities? The answer increasingly seems to be: yes, according to an update on the available evidence fom postmortem studies.

And as seems to be increasingly the picture in Alzheimer’s disease, abnormalities in different central nervous system (CNS) pathways produce a particular discrete cluster of symptoms.

The challenge is to determine if the changes identified in postmortem tissue are the result of multiple genetic mutations, or caused by changes in a few critical proteins that could severely disrupt the CNS.

Postmortem studies have suggested that neurotransmitter activity in the central nervous system is badly disrupted in schizophrenia. The changes in the dopaminergic, serotonergic, cholinergic, gulatmatergic, and GABAergic systems seem to be regionally specific, with the frontal cortex, hippocampus, and thalamus the most likely sites to be affected. And the changes seen in receptors that bind nicotine and the reactive component of cannabis add weight to the argument the people with schizophrenia may “self-medicate” with these compounds, to alleviate the symptoms these changes produce.

But there are also changes in the proteins involved in neurotransmitter release that could be involved in the pathology of schizophrenia. Interestingly, these altered proteins have been found across the various neurotransmitter systems. Recent research points to changes in the Wnt pathway, which controls gene transcription and so influences many cellular functions, including the development and function of the brain. Clearly, the pathology of schizophrenia is extremely complex, and is likely to become increasingly so as the genetic basis of the illness unfolds.