Schizophrenia: a genetic disorder of the synapse?

Glutamatergic synapses might be the site of primary abnormalities U nderstanding the cause and pathogenesis of schizophrenia remains one of the great challenges in psychiatry. Progress has been slow, but one of the few certainties is that individual differences in liability are predominantly genetic.1 This information has, however, not been useful neurobiologically because the genes themselves had not been identified. This situation is beginning to change, allowing a reappraisal of existing hypotheses of pathogenesis. Until recently the two leading hypotheses concerned dopamine and neurodevelopment. The classic dopamine hypothesis, which attributed schizophrenia to a hyperdopaminergic state, arose from the ability of dopaminergic drugs to induce a psychosis, and the realisation that the potency of antipsychotic drugs is proportional to their ability to block dopamine receptors.2 Refinements of the hypothesis indicate a more complex picture—increased dopaminergic transmission in the basal ganglia may underlie acute psychosis,3 but a prefrontal cortical …

[1]  J. Buxbaum,et al.  Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia , 2004, Nature Neuroscience.

[2]  M. Laruelle,et al.  Glutamate, Dopamine, and Schizophrenia , 2003 .

[3]  M. Owen,et al.  Recent advances in the genetics of schizophrenia. , 2003, Human molecular genetics.

[4]  Peter McGuffin,et al.  Psychiatric Genetics and Genomics , 2002 .

[5]  Daniel R. Weinberger,et al.  Prefrontal neurons and the genetics of schizophrenia , 2001, Biological Psychiatry.

[6]  J. Gorman,et al.  Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  B. Halioua,et al.  Quality of life and use of health care among people with genital herpes in France. , 1999, Acta dermato-venereologica.

[8]  J. Zeh,et al.  Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment. , 1997, The Journal of clinical investigation.

[9]  L. Corey,et al.  Risk Factors for the Sexual Transmission of Genital Herpes , 1992, Annals of Internal Medicine.

[10]  R. Murray,et al.  Is schizophrenia a neurodevelopmental disorder? , 1987, British medical journal.

[11]  D. Weinberger Implications of normal brain development for the pathogenesis of schizophrenia. , 1987, Archives of general psychiatry.

[12]  P. Seeman,et al.  Brain receptors for antipsychotic drugs and dopamine: direct binding assays. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Paul J. Harrison The neuropathology of schizophrenia , 2008 .

[14]  Paul J. Harrison,et al.  Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence , 2005, Molecular Psychiatry.

[15]  M. Laruelle,et al.  Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. , 2003, Annals of the New York Academy of Sciences.

[16]  Paul J. Harrison,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Genes for Schizophrenia? Recent Findings and Their Pathophysiological Implications , 2022 .