Sex Differences in Plasma Homovanillic Acid Levels in Schizophrenia and Normal Controls: Relation to Neuroleptic Resistance Tomiki Sumiyoshi, Mitsuru Hasegawa, Karuna Jayathilake, and Herbert Y. Meltzer Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic- resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic- resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis X gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated. © 1997 Society of Biological Psychiatry Key Words: Plasma homovanillic acid, schizophrenia, gender difference, neuroleptic resis- tance, psychopathology BIOL PSYCHIATRY1997;41:560--566 Introduction Plasma levels of homovanillic acid (pHVA), a major metabolite of dopamine (DA), have been suggested to be determined, in part, by central dopaminergic activity (Bacopoulas et al 1979; Kendler et al 1981, 1982). Since From the Laboratory of Biological Psychiatry, Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio. Address reprint requests to Herbert Y. Meltzer, MD, Department of Psychiatry, Vanderbilt University, Medical Center, 1601 23rd Ave. South, Suite 306, Nashville, TN 37212. Received September 22. 1995; revised February 5, 1996. dopaminergic abnormalities in the central nervous system are considered to be important for the pathogenesis of schizophrenia, numerous studies have been conducted to establish the relationship between pHVA levels and schizophrenia. Increased (Maas et al 1993a,b; Doran et al 1985; Pickar et al 1984), decreased (Davidson and Davis 1988), and normal (Steinberg et al 1993; Whelton et al 1993; Koreen et al 1994) pHVA levels in schizophrenia compared to normal controls have been reported. Discrep- ant results have also been reported in studies of the correlation between pHVA levels and psychopathology in © 1997 Society of Biological Psychiatry 0006-3223/97/$17.00 PII S0006-3223(96)00099-6