title: Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV.
abstract: HIV-infection is associated with neuroinflammation and greater psychopathological symptoms, which may be mediated by imbalances in the kynurenic pathway (KP). Two key KP enzymes that catabolize kynurenine include kynurenine-aminotransferase II (KATII), which yields antioxidative kynurenine acid [KYNA] in astrocytes, and kynurenine-3-monooxygenase (KMO), which produces neurotoxic metabolites in microglia. The relationships between polymorphisms in KMO and KATII, psychopathological symptoms, and cerebrospinal fluid (CSF) [KYNA] were evaluated in subjects with and without HIV-infection. Seventy-two HIV-positive and 72-seronegative (SN) participants were genotyped for KATII-rs1480544 and KMO-rs1053230. Although our participants were not currently diagnosed with depression or anxiety, they were assessed for psychopathological distress with Center for Epidemiologic Studies-Depression scale and Symptom Checklist-90-Revised. CSF-[KYNA] was also measured in 100 subjects (49 HIV/51 SN). HIV-participants had more psychopathological distress than SN, especially for anxiety. KATII-by-HIV interactions were found on anxiety, interpersonal sensitivity and obsessive compulsivity; KATII-C-carriers had lower scores than TT-carriers in SN but not in HIV. In contrast, the KMO-polymorphism had no influence on psychopathological symptoms in both groups. Overall, CSF-[KYNA] increased with age independently of HIV-serostatus, except KATII-TT-carriers tended to show no age-dependent variations. Therefore, the C-allele in KATII-rs1480544 appears to be protective against psychopathological distress in SN but not in HIV individuals, who had more psychopathological symptoms and likely greater neuroinflammation. The age-dependent increase in CSF-[KYNA] may reflect a compensatory response to age-related inflammation, which may be deficient in KATII-TT-carriers. Targeted treatments that decrease neuroinflammation and increase KYNA in at risk KATII-TT-carriers may reduce psychopathological symptoms in HIV.
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawai'i and Queen's Medical Center, 1356 Lusitana Street, 7th Floor, Room 716, Honolulu, HI, 96813, USA. vanessadouet@hotmail.com.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Douet
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawai'i and Queen's Medical Center, 1356 Lusitana Street, 7th Floor, Room 716, Honolulu, HI, 96813, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanizaki
authors.affiliation: The University of Hawai'i Cancer Center, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Franke
authors.affiliation: The University of Hawai'i Cancer Center, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors.forename: Xingnan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawai'i and Queen's Medical Center, 1356 Lusitana Street, 7th Floor, Room 716, Honolulu, HI, 96813, USA. lchang@hawaii.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology; D006801:Humans; D007736:Kynurenic Acid / Q000134:cerebrospinal fluid; D007737:Kynurenine / Q000134:cerebrospinal fluid / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales
chemical_list: D007737:Kynurenine; D007736:Kynurenic Acid
keywords: HIV; Kynurenic acid; Kynurenine 3-monooxygenase; Kynurenine aminotransferase II; Psychopathological symptoms