Polymorphisms in Kynurenine Pathway Genes and Psychological Distress in HIV Patients

Abstract

Background: HIV infection, neuroinflammation and psychopathology are each associated with imbalances in the kynurenic pathway (KP), which includes kynurenine-3-monooxygenase (KMO) and kynurenine aminotransferase II (KATII). Both KMO and KATII enzymes mediate levels of kynurenic acid (KYNA), which increases with HIV infection, and may decrease with psychopathological symptoms such as depression. Since people with HIV are more vulnerable to neuroinflammation and comorbid depression, variations in the genes of these enzymes may influence psychopathological symptoms in HIV. Methods: 72 HIV seronegative (SN) and 72 HIV positive participants were evaluated using the Center for Epidemiologic Studies Depression and Symptom Checklist-90-Revised scales, and were genotyped at KATII rs1480544 at KMO rs1053230. Cerebrospinal fluid kynurenic acid concentration [KYNA] was measured in 51 SN and 49 HIV participants. T-test, and one-way and two-way AN(C)OVA were used to compare effects of genetic variation and HIV status on psychological symptoms or KYNA levels. Pearson or Spearman analyses was used to find correlation between psychopathological symptom scores and KYNA levels. Results: For psychopathological symptoms, overall, HIV participants had higher scores than SN, and SN KATII C-carriers tended to have lower scores than SN TT homozygotes. Older age correlated with higher CSF [KYNA] in KATII C-carriers and KMO CC-homozygotes independently of serostatus. HIV participant psychopathological scores did not differ between KMO genotypes. Conclusions: KATII genotypes and HIV serostatus were associated with psychopathological symptoms. Furthermore, CSF [KYNA] varies with age depending on both KMO and KATII genotypes. Together, this supports a functional role of these variations in the dysregulation of the KP that may moderate psychopathological symptoms in HIV and SN individuals. Understanding the KP mechanisms in HIV may lead to novel treatments for psychopathological symptoms.