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Immune activation and neuropsychiatric symptoms in human immunodeficiency virus type 1 infection
Sebastian Schroecksnadel1, Katharina Kurz2, Guenter Weiss2, Dietmar Fuchs1
1Division of Biological Chemistry; 2Clinical Immunology and Infectious Diseases, Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria
Abstract: Human immunodeficiency virus type 1 (HIV-1) infection is associated with a wide range of neuropsychiatric symptoms, especially in the later course of the disease. In addition to a direct effect of HIV-1 causing irreversible loss of brain cells, neurological impairment may relate to metabolic factors. Immune activation and the inflammatory response involving immunocompetent cells seem to play a major role. Existing data suggest that immune activation and inflammatory responses can cause metabolic disturbances, which can be reversible to some extent, eg, when highly active antiretroviral therapy is successful. Immune-related tryptophan catabolism and impaired phenylalanine hydroxylase (PAH) activity have been described in HIV-1 infected patients. These enzyme systems are deeply involved in the biosynthesis of important neurotransmitters and biogenic amines like 5-hydroxytryptamin (serotonin) from tryptophan, and dopamine, adrenaline, and noradrenaline from phenylalanine. Thus, any disturbance of their biosynthesis may contribute to neurological and psychiatric symptoms, such as depression, cognitive impairment, and memory loss. In addition to highly active antiretroviral therapy, popular antidepressant medication with selective serotonin reuptake inhibitors or also noradrenaline and dopamine reuptake inhibitors will be of help to improve neuropsychiatric abnormalities in patients with HIV-1 infection. It will be interesting to know whether measurements of tryptophan degradation and of PAH activity might be able to guide treatment with antidepressants and thereby improve treatment efficacy in HIV-1 infected patients suffering from cognitive impairment, mood changes, and depression.
Keywords: HIV-1, tryptophan, neopterin, indoleamine 2,3-dioxygenase, phenylalanine
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