CLINICAL HANDBOOK OF SCHIZOPHRENIA

6. Genetics 632A receptor (HTR2A) and the dopamine D 2 (DRD2) and D 3 (DRD3) receptors. Genes codingfor disrupted-in-schizophrenia 1 (DISC1), dystrobrevin-binding protein 1 (DTNBP1),neuregulin 1 (NRG1), and regulator of G-protein signaling 4 (RGS4) have emerged asthe strongest positional candidate risk genes for schizophrenia, but these findings requireverification. The identification of numerous risk genes of varying effect on the liability towarddeveloping schizophrenia may ultimately make it possible to create a genetic riskprofile that is predictive of future onsets of the disorder. Such a genetic risk profile mayalso be used in genetic counseling settings to help potential parents understand the risk ofschizophrenia to their unborn child and to make decisions based on this information.Most relevant for the treatment of schizophrenia, several genes, including DRD2 andHTR2A, have also been reported to influence the outcome of psychopharmacological interventions.As the relationships between these genes and specific aspects of favorable orunfavorable response to antipsychotic medications become further characterized, thesetoo may attain clinical utility in the development and administration of genetically tailored,personalized medication management of schizophrenia. We must emphasize, however,that such uses of genetic data are not possible at this time and may not be possiblefor some time.KEY POINTS• Schizophrenia is a familial disorder, and the risk of schizophrenia to relatives of an affectedindividual increases as their degree of biological relationship increases.• The familial nature of schizophrenia is largely due to the transmission of genetic risk factorsthrough families; however, a sizable portion of the risk for the disorder is also influenced byenvironmental factors.• The patterns of inheritance of schizophrenia through multiply affected families are not consistentwith the effects of a single gene; rather, a multifactorial polygenic etiology is supported,in which multiple genetic and environmental factors each have a small effect onoverall risk for the disorder.• Genetic linkage analysis has revealed several “hot spots” that may harbor genes that influencethe risk for schizophrenia.• Functional candidate genes have been identified that have small effects on risk for schizophrenia;however, positional candidate genes of as yet unknown function may have evenstronger influences.• The major contributions of psychiatric genetic research to clinical psychiatry currently remainunrealized, but such research may ultimately be used to reduce uncertainty in formulatingprimary and differential diagnoses, to provide individually tailored pharmacotherapyand disease management, to enable early identification and intervention leading to betterprognoses, and ultimately to inspire effective prevention programs.REFERENCES AND RECOMMENDED READINGSBadner, J. A., & Gershon, E. S. (2002). Meta-analysis of whole-genome linkage scans of bipolar disorderand schizophrenia. Molecular Psychiatry, 7(4), 405–411.Faraone, S. V., Tsuang, M. T., & Tsuang, D. W. (1999). Genetics of mental disorders: Whatpractictioners and students need to know. New York: Guilford Press.Kety, S. S., Rosenthal, D., Wender, P. H., & Schulsinger, F. (1968). The types and prevalence of mentalillness in the biological and adoptive families of adopted schizophrenics. Journal of PsychiatricResearch, 1(Suppl.), 345–362.Kraepelin, É. (1971). Dementia praecox and paraphrenia (R. M. Barclay, Trans.). Huntington, NY:Krieger. (Original work published 1919)