During recent years the strategy for aetiological research in schizophrenia has been to concentrate on two closely connected directions: the search for the genetic element and the search for environmental factors. Damage to the immature brain during pregnancy and delivery has given us the most interesting results from recent environmental research.

To examine the validity of the influenza-schizophrenia hypothesis.

A review of register-based epidemiological studies in Denmark conducted over a 10-year period.

The studies reviewed provided strong inferential evidence in favour of the hypothesis, but some methodological problems are unresolved and not all replication studies have been positive.

The brain-damage hypothesis points to possibilities for identifying high-risk individuals at an early stage of life and perhaps establishing specific preventive programmes. There is, however, a great need for closer international collaboration in future research.

A few recent linkage studies have shown a possible locus for bipolar disorder on chromosome 18. Cytogenetic studies may assist in the further localisation of susceptibility loci on this chromosome.

A search was made for abnormalities of chromosome 18 in two separate large cytogenetic databases. In Denmark detection of mental illness in subjects with chromosome abnormalities was done by cross-linking the two separate register of psychiatric and chromosome disorders. In Scotland the Cytogenetic Registry of the MRC Human Genetics Unit undertakes long-term clinical follow-up of all cases with chromosome abnormalities.

Cross-linking the two Danish register's revealed a family with the rare karyotype abnormality inv(18) (p11.3;q21.1) with one inversion carrier who also suffered from bipolar disorder. In this family there were two other cases of bipolar disorder, but the karyotype of these cases could not be established. One family in Scotland showed a case of schizophrenia in a carrier of inv(18) with the same breakpoints as the Danish family.

We suggest further studies of the 18p11.3 and 18q21.1 regions in order to identify genes involved in bipolar affective disorder and schizophrenia.