Genetic factors that modulate the immune response have been implicated as risk factors both for schizophrenia as well as for cognitive impairments (endophenotypes of schizophrenia). Regulation of immune response is mediated by two related receptors: CD28 is a major co-stimulator, whereas CTLA-4 performs negative regulatory functions. Balance of immune response depends on the expression of these regulatory molecules due to their genes polymorphisms.

The study was carried out to investigate the association between polymorphisms of two genes: CTLA-4 (49A/G, −319C/T, CT60 A/G) and CD28 (+17C/T) and frontal lobe functions in patients with schizophrenia.

118 patients diagnosed with schizophrenia (ICD-10) and 352 controls were included in the study. Frontal lobe functioning was assessed by Trail Making Test (TMT) and Stroop Test (SCWT).

There was no significant difference in distribution of genotypes between patients and controls in the polymorphisms of CTLA-4 gene, but in polymorphism of CD28 gene (p = 0,0007). With respect to +17C/T CD28 gene polymorphism there was a trend level difference in performance on TMT: C allel carriers performed worse that T allel carriers (p = 0,054), suggesting weaker executive control function.

Our data support a role of CD28 +17 C/T gene polymorphisms for the predisposition to schizophrenia. Among patients the distribution of genotypes of CD28 gene polymorphism is similar to that found in patients with autoimmune disorders such as: early onset type 1 diabetes and Behçet's disease. Additionally, +17C/T CD28 gene polymorphism might be considered as a risk factor for cognitive impairment in schizophrenia.