The Objectives of the project are (a) to arrive at a genetically driven clinical definition of schizophrenia, and (b) to reduce heterogeneity in schizophrenia by distinguishing phenotypic subgroups on the basis of careful diagnosis and assessment of biological correlates in MZ and DZ twins.
The Specific Aims directly relate to the objectives, firstly by deriving the clinical definition of schizophrenia that has the highest genetic validity in a consecutive series of schizophrenic twins, using the MZ:DZ ratio. Such a definition will be of value in other genetic investigations such as those using linkage markers in multiplex schizophrenic families. In addition, study of the nonschizophrenic MZ co-twins will allow us to infer clinical co""""""""elates for schizophrenia with subclinical genetic penetrance.
The second aim of the study is to investigate biological correlates of schizophrenia in the same series of MZ and DZ twins, relating these to diagnosis and twin concordance in order to identify homogenous subgroups with varying genetic and other aetiological influences. As more is understood about the genetic basis of schizophrenia, so the importance of defining variants at high genetic risk vs. those non-genetic variants who do not confer risk on their biological relatives increases. Study Design: the proposal is based on the twin method, using the Maudsley Twin Register, an unparalled clinical resource of over 2000 mentally ill probands consecutively ascertained over the last 40 years. Clinical data on twins is stored in the Genetics Section, updated as the Maudsley casenotes are updated, and probands and co-twins traced to their current address at regular intervals. Thus the clinical material already available for study is impressive. The most recently ascertained cohort of 120 pairs of schizophrenic twins will be interviewed using the CASH clinical interview, and assessed using a series of paradigms which have either been implicated in aetiology or proposed as biological markers for schizophrenia. These are family history of major psychiatric disorder, motor laterality, neurological abnormality (both """"""""soft"""""""" signs and named CNS disorders) minor physical anomaly, complex continuous performance and smooth pursuit eye movements. Medical and obstetric histories will also be noted.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH044359-05
Application #
2246094
Study Section
Special Emphasis Panel (SRCM (12))
Project Start
1989-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1995-08-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of London Institute of Psychiatry
Department
Type
DUNS #
City
London
State
Country
United Kingdom
Zip Code
Cardno, Alastair G; Rijsdijk, Frühling V; West, Robert M et al. (2012) A twin study of schizoaffective-mania, schizoaffective-depression, and other psychotic syndromes. Am J Med Genet B Neuropsychiatr Genet 159B:172-82
Rijsdijk, Frühling V; Gottesman, Irving I; McGuffin, Peter et al. (2011) Heritability estimates for psychotic symptom dimensions in twins with psychotic disorders. Am J Med Genet B Neuropsychiatr Genet 156B:89-98
Cardno, Alastair G; Rijsdijk, Fruhling V; Murray, Robin M et al. (2008) Twin study refining psychotic symptom dimensions as phenotypes for genetic research. Am J Med Genet B Neuropsychiatr Genet 147B:1213-21
McGuffin, Peter; Rijsdijk, Fruhling; Andrew, Martin et al. (2003) The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 60:497-502
Cardno, Alastair G; Rijsdijk, Fruhling V; Sham, Pak C et al. (2002) A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 159:539-45
Cardno, Alastair G; Sham, Pak C; Farmer, Anne E et al. (2002) Heritability of Schneider's first-rank symptoms. Br J Psychiatry 180:35-8
Cardno, A G; Marshall, E J; Coid, B et al. (1999) Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 56:162-8