Schizophrenia: Genetics, prevention and rehabilitation: Review article

Paolo Olgiati, Laura Mandelli, Cristina Lorenzi, Elena Marino, Pirovano Adele, Barbara Ferrari, Diana De Ronchi, Alessandro Serretti

Research output: Contribution to journalArticlepeer-review


Objective Genetic factors are largely implicated in predisposing to schizophrenia. Environmental factors contribute to the onset of the disorder in individuals at increased genetic risk. Cognitive deficits have emerged as endophenotypes and potential therapeutic targets for schizophrenia because of their association with functional outcome. The aims of this review were to analyse the joint effect of genetic and environmental (G×E) factors on liability to schizophrenia and to investigate relationships between genes and cognitive endophenotypes focusing on practical applications for prevention and rehabilitation. Methods Medline search of relevant studies published between 1990 and 2008. Results In schizophrenia, examples of G×E interaction include the catechol-O-methyl transferase (COMT) (Val158Met) polymorphism, which was found to moderate the onset of psychotic manifestations in response to stress and to increase the risk for psychosis related to cannabis use, and neurodevelopmental genes such as AKT1 (serine-threonine kinase), brain-derived neurotrophic factor (BDNF), DTNBP1 (dysbindin) and GRM3 (metabotropic glutamate receptor 3), which were associated with development of schizophrenia in adulthood after exposure to perinatal obstetric complications. Neurocognitive deficits are recognised as core features of schizophrenia that facilitate the onset of the disorder and have a great impact on functional outcome. Neurocognitive deficits are also endophenotypes that have been linked to a variety of genes [COMT, neuregulin (NRG1), BDNF, Disrupted-In-Schizophrenia 1 (DISC1) and dysbindin] conferring susceptibility to schizophrenia. Recently, it has emerged that cognitive improvement during rehabilitation therapy was under control of COMT (Val158Met) polymorphism. Conclusion This review could indicate a pivotal role of psychiatric genetics in prevention and rehabilitation of schizophrenic psychoses.

Original languageEnglish
Pages (from-to)109-120
Number of pages12
JournalActa Neuropsychiatrica
Issue number3
Publication statusPublished - Jun 2009


  • Endophenotypes
  • Gene
  • Prevention
  • Rehabilitation
  • Review
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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