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Plasma beta-endorphin and withdrawal-induced anxiety in alcoholism
l?5. Addiction to blood vessels and subsequently in disruption of the BBB and leakage of neurotoxic substances. Thus, Ap may be toxic to neurons, cerebral endothelium and smooth muscle cells (SMC). Observations from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to susceptibility to AD. Patients carrying the APOE genepolymorphism, have elevated cholesterol levels and increased risk for both CAD and AD. Statins inhibit HMG-CoA reductase, the rate-limiting enzyme involved in cholesterol synthesis. Clinical trials have proven clear benefits of statin treatment in reduction of CAD mortality. However, animal studies and data from carotid endarterectomy patients (Crisby et al) demonstrate that statins induce not only plaque regression but also plaque stabilization by reducing; inflammation, oxidised low density lipoprotein, death of SMC and improving endothelial dysfunction. These so-called pleiotropic effects are suggested being mainly due to modulation of arterial gene expression and independent of statin’s lipid-lowering properties. Two recent epidemiological studies, indicate that the prevalence of AD is decreased in patients treated with statins. In the article published by Jick et al (Lancet 2000; 356: 1627-31), the prevalence for AD was reduced by 70% based on analysis of data from the UK General Practitioners Research Database. Wolozin et a (Arch Neural 2000; 57: 1439-43), studied the prevalence of AD in patients (age 1 60 years) from three different major hospitals in the United States. The diagnosis of AD was established according to the NINCDS-ADRDA criteria. The frequency of AD was studied in; a) the whole patient population, b) patients treated with statins and c) patients treated with other cardiovascular drugs including anti-hypertensive medication. The results of the analysis were astonishing. Patients treated with statins had 70% lower prevalence of AD. Of all statin drugs, lovastatin and pravastatin were the most efficacious. An interesting observation is that pravastatin, a hydrophilic statin, with the least degree of penetration to the central nervous system (CNS) was still one of the most effective statins. Two multicenter clinical trials, the CARE (Cholesterol and Recurrent Events) and the LIPID (Long-term Intervention with Pravastatin in Ischemic Disease) trial have shown reduced risk of ischemic stroke in patients treated with pravastatin. Recent reports also demonstrate that prophylactic administration of atorvastatin and mevastatin protect the brain against ischemia in experimental stroke models through upregulation of endothelial nitric oxide synthase. Hence, these observations imply that the beneficial effects of statins may be in part secondary to changes in parameters in the peripheral circulation such as generation of reactive oxygen species, modulation of extra-cranial atherosclerosis and cerebral blood flow. Although an association between cholesterol and statins has been observed in AD, clarification of the mechanisms involved in these processes needs further attention. In conclusion, the fact that statins exert an immunomodulatory and certain neuroprotective effect raises the question whether they may also play a crucial role in preventing progression of neurodegeneration involved in AD.
S329
P.5. Addiction Ip.5.001]Plasma
beta-endorphin and withdrawalinduced anxiety in alcoholism
F. Kiefer, M. Horntrich, H. Jahn, J. Arlt, I? Ktipf, K. Wolf, K. Wiedemann. University Hospital EppendorJ Dept. of Psychiatry and Psychotherapy, University of Hamburg, Germany Significant associations between anxiety and lowered p-endorphin (PE) plasma levels have been reported repeatedly. Especially in contrast to single measures during static conditions, associations of psychopathology with dynamic changes of PE concentrations have been shown to be relevant e.g. during the premenstrual syndrome and in depression after dexamethasone challenges. Also in chronic alcoholism, an altered secretion of @E has been described previously, however, only few data about the interaction of plasma BE and psychopathological parameters are available. Whereas chronic alcohol exposure has shown a rather blurred picture of the brain and pituitary content of PE, during alcohol withdrawal @Elevels consistently are lower than normal. Aim of our study was to prove whether PE during acute alcohol withdrawal is associated with psychopathologic disturbances. We observed self rated anxiety (VAS), depression (SDS), and craving (OCDS) during alcohol withdrawal and assessed PE levels @IA) in a consecutive sample of 60 alcoholics at day 1 and day 14 afier onset of withdrawal, and in 30 healthy volunteers. To control for mutual interactions of PE and the pituitary-adrenocortical hormone secretion, plasma corticotropin (ACTH) and cortisol were also determined. In accordance with prior studies, PE was significantly lowered at day 1 (64.6 & 30.1 pg/ml) and day 14 of alcohol withdrawal (65.9 f 21.3 pg/ml) compared to controls (77.4 f 25.3 pg/ml). Plasma levels of ACTH correlated significantly with PE in alcoholics at both timepoints and in controls (r = 0.6; p < O.OOl), without differing significantly between the groups. As reported before, plasma cortisol was elevated at onset of withdrawal (254 & 91 ng/ml) decreasing significantly until day 14 (185 f 50 @ml; p < 0.05; controls: 163 * 98 @ml; p < 0.01). Self rated anxiety, depression, and alcohol craving decreased significantly between day 1 and day 14. Levels of PE were inversely correlated with anxiety at day 1 (r = -0.58; p < 0.001) and day 14 (r = -0.71; p < 0.001). Partial correlation coefficients controlling for ACTH plasma levels revealed that this correlation is largely independent from ACTH. No association appeared between PE and depression or craving. Our results give first evidence that lowered @E levels may contribute to anxiety during alcohol withdrawal.
-1
Gender differences in the psychotropic effects of MDMA (“Ecstasy”)
M.E. Liechti, A. Gamma, EX. Vollenweider. Uniuersi@ Hospital of Psychiatry Zurich, Clinical Research Unit, PO Box 68, CH-8029 Zurich, Switzerland Introduction: 3,4-Methylenedioxymethamphetamine (MDMA) is the main component of the recreational drug Ecstasy. MDMA releases serotonin (5-HT) and to a lesser extent dopamine (DA). 5-HT plays an important role in mood and anxiety disorders, for which there is a female over male preponderance. The present study assessed gender differences in the subjective effects of MDMA.
S329
P.5. Addiction Ip.5.001]Plasma
beta-endorphin and withdrawalinduced anxiety in alcoholism
F. Kiefer, M. Horntrich, H. Jahn, J. Arlt, I? Ktipf, K. Wolf, K. Wiedemann. University Hospital EppendorJ Dept. of Psychiatry and Psychotherapy, University of Hamburg, Germany Significant associations between anxiety and lowered p-endorphin (PE) plasma levels have been reported repeatedly. Especially in contrast to single measures during static conditions, associations of psychopathology with dynamic changes of PE concentrations have been shown to be relevant e.g. during the premenstrual syndrome and in depression after dexamethasone challenges. Also in chronic alcoholism, an altered secretion of @E has been described previously, however, only few data about the interaction of plasma BE and psychopathological parameters are available. Whereas chronic alcohol exposure has shown a rather blurred picture of the brain and pituitary content of PE, during alcohol withdrawal @Elevels consistently are lower than normal. Aim of our study was to prove whether PE during acute alcohol withdrawal is associated with psychopathologic disturbances. We observed self rated anxiety (VAS), depression (SDS), and craving (OCDS) during alcohol withdrawal and assessed PE levels @IA) in a consecutive sample of 60 alcoholics at day 1 and day 14 afier onset of withdrawal, and in 30 healthy volunteers. To control for mutual interactions of PE and the pituitary-adrenocortical hormone secretion, plasma corticotropin (ACTH) and cortisol were also determined. In accordance with prior studies, PE was significantly lowered at day 1 (64.6 & 30.1 pg/ml) and day 14 of alcohol withdrawal (65.9 f 21.3 pg/ml) compared to controls (77.4 f 25.3 pg/ml). Plasma levels of ACTH correlated significantly with PE in alcoholics at both timepoints and in controls (r = 0.6; p < O.OOl), without differing significantly between the groups. As reported before, plasma cortisol was elevated at onset of withdrawal (254 & 91 ng/ml) decreasing significantly until day 14 (185 f 50 @ml; p < 0.05; controls: 163 * 98 @ml; p < 0.01). Self rated anxiety, depression, and alcohol craving decreased significantly between day 1 and day 14. Levels of PE were inversely correlated with anxiety at day 1 (r = -0.58; p < 0.001) and day 14 (r = -0.71; p < 0.001). Partial correlation coefficients controlling for ACTH plasma levels revealed that this correlation is largely independent from ACTH. No association appeared between PE and depression or craving. Our results give first evidence that lowered @E levels may contribute to anxiety during alcohol withdrawal.
-1
Gender differences in the psychotropic effects of MDMA (“Ecstasy”)
M.E. Liechti, A. Gamma, EX. Vollenweider. Uniuersi@ Hospital of Psychiatry Zurich, Clinical Research Unit, PO Box 68, CH-8029 Zurich, Switzerland Introduction: 3,4-Methylenedioxymethamphetamine (MDMA) is the main component of the recreational drug Ecstasy. MDMA releases serotonin (5-HT) and to a lesser extent dopamine (DA). 5-HT plays an important role in mood and anxiety disorders, for which there is a female over male preponderance. The present study assessed gender differences in the subjective effects of MDMA.