Immunoglobulin genotypes and cognitive functions in schizophrenia

Exposure to neurotropic viruses, such as herpes simplex virus type 1 and human cytomegalovirus, has been reported to be associated with cognitive impairment in schizophrenia. These viruses have evolved highly sophisticated strategies for decreasing the efficacy of the host immune response and interfering with viral clearance. Particular immunoglobulin GM (γ marker) genotypes modulate these viral immunoevasion strategies, influence antibody responsiveness to viral proteins, and are also associated with susceptibility to schizophrenia, providing an excellent rationale for determining their possible involvement in the cognitive functions in this highly heritable neurodevelopmental disorder. In this investigation, we assessed the cognitive functions (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function) in 145 patients with schizophrenia and characterized their DNA for several GM and KM (κ marker) alleles. Particular KM and GM genotypes were significantly associated with verbal memory and attention and processing speed scores, respectively (P = 0.01 and 0.001). Epistatic effects of GM and KM genotypes on attention and processing speed, verbal fluency, and motor speed were also noted (P = 0.031, 0.047, 0.003). These results, for the first time, show that hitherto understudied immunoglobulin GM and KM genotypes—individually and epistatically—contribute to the magnitude of interindividual variability in the cognitive functions in patients with schizophrenia. Additional studies involving these highly polymorphic genes of the immune system are needed.