Gonadotropin activity in men and women with schizophrenia

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provided an inherently unbalanced data set, with patients having variable numbers of observations. Random regression (individual effects modelling) was used to determine patterns of the dopaminergic metabolite plasma homovanillic acid (HVA) and the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) over time. Plasma HVA levels were highly variable following haloperidol withdrawal and could not be summarized using genera1ized linear techniques, while plasma MHPG levels showed a quadratic pattern which was different for relapsed and nonrelapsed patients. While both groups of patients had a decrease in MHPG levels followed by an increase over time, levels in relapsing patients increased sooner. Becauseboth plasma measures were evaluated from the same assay, it appears that assay variability does not explain the results. Random regression was shown to be highly useful in the analysis of biochemical changes in schizophrenic patients.

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ANTICARDIOLIPIN ANTIBODIES IN SCHIZOPHRENIA Galina I. Kolyaskina, Olga A. Burbaeva, Tatiana P. Sekirina Laboratory ofClinicalNeuroimmunology, National Mental Health Research Center, Zagorodnoe Sh 2 Moscow, 113152 Russia

Disturbances in phospholipid metabolism have been suggested in schizophrenia. It is possible that antiphospholipid antibodies may be important factors in the formation of these disturbances. Anticardiolipin antibodies (ACA) were studied in the blood serum of 20 patients with an ICD-IO diagnosis of schizophrenia (SZ) and 16normal controls (NC) using ELISA. SZ were examined twice in relapse and in remission after treatment with psychothropic drugs. It was demonstrated that the average titre of ACA in SZ was much higher than in NC (p <0.05). The analysis of the distribution of examined persons with high, middle and low titre of ACA showed that 17% of NC had a low titre of ACA, 67"/..--middle and 16% a high ones. In the group of SZ 10% had low titre of ACA 40%-middle and 50% - high ones. Treatment of SZ by psychothropic drugs reduced ones and after some times the titres of ACA in the SZ and NC groups become equal. Whether or not ACA are implicated in the mechanisms of phospholipid metabolism disturbances and related to the pathogenesis of schizophrenia needs to be determined.

'71 INCREASED CYCLOOXYGENASE/ LIPOOXYGENASE ACfIVITY IN PLATELETS FROM SCHIZOPHRENIC SUBJECTS INDICATES IMPAIRED ARACHIDONIC ACID METABOLISM Nusrat S. Khan, Indrajit Das, Basant K. Puri and Steven R. Hirsch Academic Department ofPsychiatry, Charing Cross & Westminster Medical School, London W68RP, UK

It was observed that arachidonic (AA), linoleic and linolenic acid can cause luminol-induced chemiluminescence in human platelets indicating the formation of reactive oxygen species by cyclooxygenase and/or lipooxygenase. Clinical and basic biochemical studies imply that the membrane phospholipid fatty acids, AA and docosahexanoic acids are important determinants of brain membrane functions. Abnormalities of these fatty acids in peripheral and neuronal cell membranes have been found in schizophrenia. The aim of this project is to investigate AA, linoleic and linolenic acid metabolism in platelets of schizophrenic patients by cyc1ooxygenasejlipooxygenaseinduced chemiluminescence. Blood samples from schizophrenic patients meeting DSM I1I-R criteria for schizophrenia and healthy control subjects were used. Platelets were isolated and incubated with luminol. AA, linoleic and linolenic acidinduced chemiluminescence was measured in a LKB-Wallac Luminometer and was shown to be dose-dependent. Platelets of drug naive schizophrenic patients showed significantly increased arachidonic acid metabolism compared to control subjects; this was seen to be normalised in patients subsequently treated with neuroleptics for 3 months. No significant difference was observed between schizophrenic and control subjects in chemiluminescence response induced by linoleic acid before or after drug treatment. Our studies indicate that cyclooxygenase/ lipooxygenase pathway is hyperactive in schizophrenic platelets which is normalised after drug treatment. Linoleic acid is not a prostaglandin precursor which may explain why it is shown not to be directly involved in schizophrenia. A similar condition may exist in the brain.

/71GONADOTROPIN ACTIVITY IN MEN AND WOMEN WITH SCHIZOPHRENIA Kulkarni J, de Castella A, Taffe J. Research Groupfor Womens Mental Health, Monash University, Dandenong Hospital, 134 Cleeland Street, Dandenong, Victoria 3175, Australia

Gender differences in psychotic symptoms have been described in clinical research. 36 patients with schizophrenia (19 males, 17 females) and 34 controls (18 males, 16 females) were studied. Baseline measures of lutenising hormone, follicle stimulating hormone, estrogen and progesterone were compared between sex, age and menstrual cycle phase matched groups of patients and controls. The gonadotropin response to lOmg intravenous naloxone challenge was then measured, and six 10ml peripheral blood samples were taken at 20 minute intervals. Male patients had significantly higher LH and testosterone levels compared with male controls. There was a positive correlation between mean" testosterone levels and negative psychotic symptoms. Female patients had significantly higher LH levels and very low estrogen levels compared with female controls. Positive and negative psychotic symptoms were negatively correlated with estrogen levels. Peak responses to naloxone challenge varied between patient and control groups.

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The male patients had a "puberty-like" hypothalamopituitary-gonadal (HPG) axis profile while the female patients had a " menopause-like" HPG axis profile, compared with age matched controls. This study supports a sex hormone basis for gender differences in schizophrenia and hormonal treatments such as with estrogen supplementation, may be useful

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MENSTRUAL CYCLE CHANGES IN SCHIZOPHRENIA

Kulkarni J, de CasteIla A, Thompson K, Smith D.

nicotine. probably by deeper inhalation of cigarettes. Schizophrenic patients' higher dose of nicotine may target different receptors than those activated by the lower doses selfadministered by most non-schizophrenic smokers. In particular. high doses may activate low affinity alpha-? nicotinic receptors, associated with deficits in sensory inhibition in schizophrenia.

11S PLASMA TBARS LEVELS IN UNMEDICATED CHRONIC SCHIZOPHRENIC PATIENTS Malcolm Peet, Zhi Jun Zhang, K Selvam,

CN Ramchand Research Groupfor Womens Mental Health, Monash University. Dandenong Hospital, 134 CleelandStreet, Dandenong, Victoria 3175, Australia Literature supporting a close association between menstrual cycle phase and psychosis exacerbation or onset is mainly found in the form of case reports and anecdotal clinical reports . A Menstrual Cycle Interview (MCI) was developed and validated by serum LH/FSH/progesterone and estrogen measurements. This instrument was administered to 81 patients with schizophrenia and 57 controls. The main findings were that 41.9% of the patient population had irregular cycles compared to 7% of controls. Controls were significantly older than patients at menarche. Amenorrhoea was present in 50% of patients . Controls experienced more somatic premenstrual syndrome symptoms compared with patients. 3lout of 81 patients experienced exacerbation of positive psychotic symptoms in the premenstrual period . Both patients and controls were equally reliable in providing menstrual cycle information, when cycle phase estimates from the MCI were compared with result of hormone assays. The studies suggest that using the MCI plus hormone assays provide a useful tool to include menstrual cycle phase as a variable in research studies. Menstrual irregularities may reflect abnormal hypothalamo-pituitary-gonadal axis function in schizophrenia and need further examination .

111 INCREASED LEVELS OF THE NICOTINE METABOLITE COTININE IN SCHIZOPHRENIC SMOKERS COMPARED TO OTHER SMOKERS Ann Olincy, David A. Young, Robert Freedman

University of Colorado Health Sciences Center. Box C-268-71. 4200 E 9th Ave, DenverCO 80262 The purpose of this study was to determine if schizophrenic patients self-administer more nicotine during cigarette smoking than non-schizophrenic subjects. Urinary cotinine, a nicotine metabolite, was measured in twenty schizophrenic patients and twenty non-schizophrenic subjects with similar smoking history . Schizophrenic patients had significantly higher urinary cotinine levels suggesting that schizophrenics consume higher doses of

Department ofPsychiatry, NorthernGeneral Hospital. Herries Road, Sheffield S5 7A U. UK

It has been suggested that indices of lipid peroxidation are increased in schizophrenia but most studies are confounded by possible effects of medication. One study has found increased levels of thiobarbituric acid reactive substances (TBARS) in drug -naive patients at the onset of psychosis. We have measured plasma TBARS in a group of 63 unmedicated schizophrenic patients hospitalised in Malaysia (drug free for average )4.4 years, predominant negative symptomatology, mean age S9 years; 48M, 15F) and compared these to 67 healthy control subjects from the hospital staff (mean age 44 years; 41M, 26F). Plasma TBARS was significantly elevated in the drug free schizophrenic group relative to controls (I.1S±O.43 versus 0.93 ± 0.39. p =0.(03). This suggests that increased free radical activity is involved in the schizophrenic disease process. n~

BIOCHEMICAL ALTERATIONS ASSOCIATED WITH MEMBRANE PATHOLOGY IN SCHIZOPHRENIA. A STUDY USING FIBROBLASTS FROM SCHIZOPHRENICS CN. Ramchand, I. Das, R. Ramchand, K.H. Lee and

M. Peet Department of BiomedicalScience. University ofSheffield. SI01TN. UK Studies have shown that psychotic patients have functional membrane abnormalities such as altered ion transport, hormone stimulated adenyl cyclase activity, drug and neurotransmitter receptor binding. It has also been shown that fatty acid metabolism is impaired in schizophrenia and that patients can bedivided into positive and negative syndrome types based on memb~e fatty acid composition. It is not known whether these abnorma1ities are associated with neuroleptic therapy, disease pr~ environmental factors such as diet or a genetic defect Studies using cultured cellscan avoid extraneous effects. Wehavestudied several parameters related to membrane pathology using skin fibroblasts from patients and controls. No alterations werefound in the rate of growth or doubling time in the fibroblasts. There were significantly increased levels of polyamines and glucose