Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10

Abstract

Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n = 72), random controls (n = 225) and hospital-patient controls (n = 36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P = 1.39 Â 10 À10 , odds ratio (OR) = 9.43), especially with Chlamydophila psittaci (P = 2.81 Â 10 À7, OR = 24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P = 8.03 Â 10 À5 , OR = 50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

“…Other researchers reported similar associations between schizophrenia risk and other human pathogens, supporting the gene-infection interaction hypothesis [198][199][200][201]. This research line on the effects of interaction between genes or genetic variants on the risk of schizophrenia related to T. gondii parasitization is highly likely to establish the true causes of the disease, at least in some types of patient.…”

Clinical studies of neuroinflammatory mechanisms in schizophrenia

“…Several immune-related genes share this region. The most significant gene associations were with HLA complex genes that moderate the inflammatory response (Fellerhoff et al, 2007), histone genes that focus on antimicrobial defense (Kawasaki and Iwamuro, 2008) and histone proteins potentially involved in DNA repair and methylation (Costa et al, 2009;Kundakovic et al, 2007). A meta-analysis complied many of the genetic studies to date and was able to pinpoint specific variants of immune-related genes in schizophrenia (Ripke et al, 2013).…”

Paradoxical downregulation of HLA-A expression by IFNγ associated with schizophrenia and noncoding genes

“…The selection of microbial peptides also appears to be influenced by genetic variants of TAP (transporter associated with antigen processing) and the chaperon tapasin in schizophrenic patients (Fellerhoff and Wank 2009). The stimulation of these systems may partially explain the successes observed in case reports of adoptive immunotherapy for patients with schizophrenia and other mental disorders (Fellerhoff et al 2007;Laumbacher et al 2005).…”

“…We later verified Chlamydiaceae infections by nested PCR and sequence based typing, which were observed six times more often in the blood and four times more often in blinded brain samples of patients with schizophrenia compared to controls (Fellerhoff et al 2007;Fellerhoff and Wank 2011). Furthermore, there was a fifty-fold increased risk for Chlamydia-infected individuals to succumb to schizophrenia if they had inherited the HLA-A10 antigen (Fellerhoff et al 2007). We therefore were interested in whether HLA-A10 was properly expressed and whether it could affect the immune response against Chlamydia.…”

“…Although chronic infections have been found to be significantly more frequent in patients with schizophrenia (Yolken and Torrey 1995;Karlsson et al 2001;Fellerhoff et al 2007), it has remained unclear how the function of the CNS could be so deeply affected by failing immune responses. It is also unclear how schizophrenia-associated immune gene variants of the HLA system could have such a significant impact on the function of the CNS.…”