Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

Objectives: Genetic associations between delusional disorder and paranoid schizophrenia are not well understood, although involvement of biological factors has been suspected. We investigated the incidence of human leukocyte antigen (HLA) class I alleles in patients with delusional disorder and paranoid schizophrenia, first, to explore a possible immunogenetic etiology of these paranoid disorders and, second, to determine whether they share similar etiologic mechanisms. Method: We employed a nested case–control study design. Psychiatric reference data were available for 38500 patients attending a hospital-based psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients with delusional disorder and 50 patients with paranoid schizophrenia as the subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy volunteers matched for age and ethnic background as control subjects. All subjects came from an India-born Bengali population. We applied the polymerase chain reaction–based molecular typing method to all patients and healthy subjects. Results: The HLA-A*03 gene is significantly associated with delusional disorder as well as with paranoid schizophrenia. This HLA gene alone or in linkage disequilibrium with other HLA genes or other closely linked non-HLA genes may influence susceptibility to delusional disorder and paranoid schizophrenia. Conclusions: The study reveals important associations between HLA genes and paranoid disorders. Delusional disorder and paranoid schizophrenia may share similar etiologic mechanisms. This preliminary observation may help our understanding of the genetic basis of these paranoid disorders.