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One may speculate about some far future in which individuals will routinely undergo 'genic analysis', as nowadays they are routinely vaccinated...Perhaps massive genic analysis of the population will eventually give us the information that will lead to working out the physical basis for mental disease.
Isaac Asimov (1962). The Genetic Code. The New American Library, Inc.
Schizophrenia is a chronic and severe mental illness defined by the presence of delusions and hallucinations (positive symptoms), apathy and social withdrawal (negative symptoms), and specific cognitive failures (Ref. 1). It is diagnosed through qualitative assessment of patient interview and case notes with reference to an agreed set of classification criteria. The absence of objective biological tests for schizophrenia (e.g. through blood sample analysis or physiological readout) is a hindrance to disease prediction, diagnosis, therapeutic assessment and scientific research. The intangibility of the diagnosis results from the difficulties in assessing the living brain in conjunction with the substantial heterogeneities in biological origin and clinical presentation of the disorder.
In this regard, a detailed description of the biology of schizophrenia would be invaluable. Traditionally, such a description has been based on three principal observations. First, there is the pharmacologically defined involvement of specific neurotransmitter receptor systems and their particular anatomical pathways in the brain. The action of amphetamine in inducing or worsening psychotic symptoms suggested that dopaminergic hyperactivity is an important component of illness. Further elucidation of the key dopaminergic tracts in the brain affected by receptor-blocking antipsychotic medication explained both the alleviation of positive symptoms and motor-control side effects. Hypofunction of the glutamatergic neurotransmitter system is also implicated through the action of neurotransmitter receptor antagonists, such as phencyclidine (PCP) and ketamine, together with expression studies that show reduced subunit expression in post-mortem brain samples from individuals diagnosed with schizophrenia (Ref. 2). Second, evidence from brain-imaging approaches has provided evidence for regional brain abnormalities in structure - implicating neurodevelopment - and function associated with illness. Some of these features correlate with genetic risk status, as recently reviewed (Ref. 3). Third, particular cellular pathologies have been described in brains from patients diagnosed with schizophrenia: for example, reduced oligodendrocyte number (Ref. 4) or altered neuronal cytoarchitecture (Ref. 5). Until recently, these 'high-level' observations, although highly...