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

Abstract

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 38 500 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. Clinical Implications· This preliminary study may help us to understand the genetic basis of delusional disorder and paranoid schizophrenia. · This investigation may further help in understanding whether delusional disorder and paranoid schizophrenia bear similar etiologic mechanisms based on HLA associations. · The study may strengthen our knowledge of the paranoid spectrum concept. Limitations· The sample size was small, and the study needs to be replicated in a large sample. · We studied the distribution of HLAs in delusional disorder as a whole, rather than by subtype. · We did not study the familial clustering pattern of these HLA genes.

The Case for Autoimmunity in the Etiology of Schizophrenia

“…67 The authors of another study proposed that HLA-G antigens are pivotal in the development of schizophrenia. 68 Further positive statistical associations between particular HLA alleles and the development of schizophrenia have been found with HLA-A10*03, 69 HLA-DRB1, 70 and HLA-B15. 56 Negative associations have been found with HLA-B35, 56 HLA-DQB1, 71 and HLA-DQB1*0402.…”

Aberrant Gray Matter Volume and Cortical Surface in Paranoid-Type Delusional Disorder

“…Morimoto et al [11] described dopamine system dysregulation in persecutory DD, as shown by elevated levels of plasma homovanillic acid and polymorphisms of dopaminergic receptor genes such as DRD2 and DRS 3. Furthermore, an association of HLA-A*03-Gen [19] has been found. In previous neuroimaging studies, structural and functional abnormalities in distinct frontotemporal regions, anterior cingulate cortex and insula were frequently observed [20,21].…”

Recent developments in the management of delusional disorders

“…The limited work on the diagnostic relationships of delusional disorder include a study of monozygotic/dizygotic concordance rates for schizophrenia spectrum disorders, which found that delusional disorder is unlikely to be related to them (Farmer 1987). This is supported by more recent genetic research evidence, which suggests that delusional disorder has no relation to the dopamine D 1 receptor gene (Debnath 2010). There is a school of thought that considers delusional disorder to relate more naturally to a currently disparate group of disorders that contain both obsessional and delusional components (Fear 2000;O'Dwyer 2000;see also Hollander (1993) and Hollander et al (2011) for detailed commentary).…”