It is well established that schizophrenia has a sizeable genetic component and that schizotypy may share common genetic vulnerability with schizophrenia. Meehl (1989) postulated the concept of schizotaxia, anunderlying genetic vulnerability to both schizophrenia and schizotypy. Schizotaxia is apparent in 20–50% of first-degree relatives of people with schizophrenia. It is thus clear that the underlying genetic vulnerability does not necessarily lead to either schizophrenia or schizotypy.
Studies have shown that clinical symptoms in first-degree relatives of people with schizophrenia include negative symptoms which are similar in nature to (but less severe than) those seen in schizophrenia (e.g. Kendler et al, 1995).
Positive symptoms tend to be less evident than in schizophrenia or schizotypy, but neuropsychological impairments are also seen. Schizotypal features are more common in first-degree relatives of people with schizophrenia and mirror the symptom dimensions of schizophrenia. Updating the concept of schizotaxia, Andreasen (1999) suggested a view of schizophrenia as involving abnormal connections in the cortico-cerebellar–thalamic–cortical circuit (normally used to coordinate both motor and mental activity).
These lead to misconnections in many aspects of mental activity, or ‘cognitive dysmetria’. It has recently been reported that the anatomical changes underlying cognitive dysmetria may also underlie the early developmental abnormalities seen in schizophrenia (Ridler et al, 2006).
Genetic studies of schizophrenia have suggested several chromosomal regions that appear to be linked with the disorder (Berry et al, 2003). Findings from investigations of candidate genes have often not been consistently replicated. However, there have been recent advances, with the identification of several putative susceptibility genes that may be involved in synaptic function and organisation (Harrison & Weinberger, 2005).
These findings provide support for the neurodevelopmental hypothesis of schizophrenia, as well as providing a possible link between genetic susceptibility factors and the observed neuroanatomical abnormalities. Interest has also focused on the possible role of epigenetic factors in schizophrenia (i.e. there may be factors other than specific gene sequence that can affect the way a disorder is inherited) and on the identification of particular endophenotypes (Gottesman & Gould, 2003) under genetic control (Berry et al, 2003).
References
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn). APA.
Andreasen, N. C. (1999) A unitary model of schizophrenia: Bleuler’s “fragmented phrene” as schizencephaly. Archives of General Psychiatry, 56, 781–787.
Asarnow, J. R., Tompson, M. C. & Goldstein, M. J. (1994) Outcome in childhood-onset schizophrenia-spectrum disorders. Schizophrenia Bulletin, 20, 599–617.
Asarnow, J. R., Tompson, M. C. & McGrath, E. P. (2004) Childhood-onset schizophrenia: clinical issues. Journal of Child Psychology and Psychiatry, 45, 180–194.
Bellgrove, M. A, Collinson, S., Mattingley, J. B., et al (2004) Attenuation of perceptual asymmetries in patients with early-onset schizophrenia: evidence in favour of reduced hemispheric differentiation in schizophrenia? Laterality, 9, 79–91.
Berry, N., Jobanputra, V. & Pal, H. (2003) Molecular genetics of schizophrenia: a critical review. Journal of Psychiatry and Neuroscience, 28, 415–429.
Birchwood, M., Todd, P. & Jackson, C. (1998) Early intervention in psychosis. The critical period hypothesis. British Journal of Psychiatry (suppl. 33), 172, 53–59.
Bleuler, E. (1911) Dementia Praecox or the Group of Schizophrenias. Reprinted 1950. International University Press.
Bracha, H. S., Torrey, E. F., Bigelow, L. B., et al (1991) Subtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin study. Biological Psychiatry, 30, 719–725.
Eric J. Davies
Eric Davies is Consultant Child and Adolescent Psychiatrist working with the 5 Boroughs Partnership NHS Trust (The Elms, 50 Cowley Hill Lane, St Helens, Merseyside WA10 2AW, UK. Email: eric.davies2@5bp.nhs.uk). He trained at the University of Manchester, where he also completed a PhD on factors related to genetic susceptibility in systemic lupus erythematosus. He has a particular interest in the genetics of schizophrenia and is an Honorary Research Fellow in the Division of Psychiatry at the University of Manchester.
