title: Platelet MAO activity during treatment with pegylated interferon-alfa in melanoma patients.
abstract: Depression and cognitive disturbance are well-known neuropsychiatric side effects of therapy with interferon-alfa (IFN-alfa). Aggression and irritability are also reported as side effects. Probably, central nervous system (CNS) serotonergic dysfunction is one of the underlying pathophysiological mechanisms of IFN-alfa-induced neuropsychiatric toxicity. Platelet activity of monoamine oxidase-B (MAO; EC1.4.3.4) is a possible indicator of central serotonergic function. Moreover, low platelet MAO activity is linked to impulsiveness, addiction and personality disorder. In this exploratory study in 17 high-risk melanoma patients, platelet counts, whole blood MAO, and platelet MAO activity were measured before and during therapy with IFN-alfa. Patients were randomized to treatment either with pegylated IFN-alfa (PEG-IFN-alfa) once a week at a dose of 6 microg/kg/week subcuteanously (s.c.) during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. for a total of 5 years, or to observation only. Blood samples were taken at baseline, 4 and 8 weeks and 3 months. During treatment with IFN-alfa, platelet counts decreased at 4 and 8 weeks and 3 months, while platelet MAO activity increased, both compared to baseline and compared to non-treated controls. Compared to non-treated controls, platelet MAO activity increased with 86.4% (95 CI: 52.9-127.2). No significant changes in platelet MAO activity were observed in the control group. This indicates that platelet MAO activity is influenced by IFN-alfa. Since platelet MAO activity is a model for CNS MAO-B activity, it may be speculated that CNS MAO-B activity will also be increased. This could influence serotonin (5-HT) metabolism and thereby contribute to the development of psychiatric disturbance. However, a preferential inhibition of platelet production cannot be ruled out. Hypothetically, the antiproliferative effects of IFN-alfa could interfere more strongly with the synthesis of platelets than with the synthesis of mitochondria. In that case, increased platelet MAO activity reflects an increased number of mitochondria per platelet.
authors.affiliation: Department of Psychiatry, Erasmus MC-Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands. m.bannink@erasmusmc.nl
authors.forename: Marjolein
authors.initials: M
authors.lastname: Bannink
authors.forename: Wim H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Van Gool
authors.forename: Paul G H
authors.initials: PG
authors.lastname: Mulder
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Gerrit
authors.initials: G
authors.lastname: Stoter
authors.forename: Durk
authors.initials: D
authors.lastname: Fekkes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000201:enzymology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology*; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000097:blood*; D010976:Platelet Count; D011092:Polyethylene Glycols
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D008995:Monoamine Oxidase