title: Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid.
abstract: Human immunodeficiency virus type 1 (HIV-1) infection is associated with psychiatric complications including cognitive impairment, affective disorders, and psychosis. Previous studies have revealed a disturbed kynurenine metabolism in these patients leading to increased levels of neuroactive compounds acting at glutamatergic neurotransmission. Kynurenic acid (KYNA), one of these metabolites is a glutamate-receptor antagonist, preferentially blocking the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Increased levels of brain KYNA have been suggested to induce a NMDA receptor hypofunction that is associated with psychotic symptoms. In the present study, we analyze the concentration of KYNA in the cerebrospinal fluid (CSF) from HIV-1 infected patients (n=22), including HIV-1 infected patients with psychotic symptoms (n=8) and HIV-1 infected patients without psychiatric symptoms (n=14). We found that HIV-1 infected patients had significantly higher median concentration of CSF KYNA (3.02nM) compared to healthy controls (1.17nM). Furthermore, CSF KYNA levels were significantly elevated in HIV-1 infected patients with psychotic symptoms (4.54nM) compared to patients with HIV-1 without psychiatric symptoms (2.28nM). Present results indicate that increased levels of CSF KYNA may be associated with development of psychotic symptoms in HIV-1 infected patients.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. ann.atlas@karolinska.se
authors.forename: Ann
authors.initials: A
authors.lastname: Atlas
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
authors.forename: Conny
authors.initials: C
authors.lastname: Nordin
authors.forename: Leif
authors.initials: L
authors.lastname: Lindström
authors.forename: Lilly
authors.initials: L
authors.lastname: Schwieler
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007736:Kynurenic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000821:virology; D012313:RNA / Q000032:analysis; D012016:Reference Values
chemical_list: D012313:RNA; D007736:Kynurenic Acid