Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder

Schizophrenia and affective psychoses are severe and prevalent psychiatric disorders described in all cultures and populations. Whether these functional psychoses are two distinct disorders, or are closely related in aetiology, has been debated in the literature during the last century.1–4 Several studies have suggested that schizophrenia and bipolar disorder are on a continuum of liability. Psychopathological dimensions and psychiatric symptoms shared by both groups of patients would be compatible with this overlap.5 Likewise, other risk factors, such as cerebral ventricle enlargement,6 markers of prenatal suffering,7 or life events,8 have been described in both mental disorders. Recent molecular linkage studies have suggested the possible existence of shared disease loci for both disorders.9 Of special interest are the family studies showing that first degree relatives of bipolar patients have a three times increased risk for schizophrenia compared with first degree relatives of controls.10,11 These data suggest the presence of a common genetic risk background in both disorders. However, it should be noted that other family studies have not been able to replicate these latter results.12,13 Over the last decade, several studies have reported an imbalance in pro-inflammatory/anti-inflammatory cytokines or their soluble receptors level in plasma or cerebrospinal fluid of schizophrenic and bipolar disorder patients.14,15 These results have been replicated by recent studies in both diagnostic groups.16,17 Genes coding for some of these cytokines are located on the IL-1 cluster within chromosome 2q13. This cluster contains nine genes of the IL-1 family of cytokines ( IL-1A , IL-1B , IL-1RN , and IL-1F5–F10 ).18 Several polymorphic variants of these genes have been associated with human diseases.19 The IL-1β gene ( IL-1B ) consists of seven exons with an extension of 7 kb and codes for a precursor form (proIL-1β) …