1 Department of Psychiatry, 2 Paik Institute for Clinical Research and 3 Pharmacogenomics Research Center, Inje University, Busan and 4 Department of Psychiatry, Dongsuh Hospital, Masan, Korea, and 5 Maryland Psychiatric Research Center, University of Maryland Baltimore, MD, USA
* Author to whom correspondence should be addressed at: Department of Psychiatry, Busan Paik Hospital 633-165 Gaegum-Dong, Busanjin-Gu, Busan 614-735, Republic of Korea. Tel.: +82 51 890 6386; Fax: +82 51 894 2532; E-mail: jooshim{at}inje.ac.kr
(Received 2 January 2004; in revised form 10 February 2004; accepted 26 March 2004)
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ABSTRACT |
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INTRODUCTION |
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Cortisol response to buspirone, 5-HT1A partial agonist, has been used for the evaluation of 5-HT1A receptor sensitivity in many psychiatric disorders (Meltzer and Maes, 1994). In the present study, we evaluated cortisol response to buspirone in extended abstinent alcoholic patients to determine if 5-HT1A receptor sensitivity is related with pathophysiology of alcoholism.
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MATERIALS AND METHODS |
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RESULTS |
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DISCUSSION |
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Little is known about serotonin dysfunction in regards to relapse of alcoholic patients. It has been reported that high concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, in cerebrospinal fluid was related to relapse (George et al., 1999) but this finding has not been replicated. Thus far, several serotonergic drugs have been tried in alcoholic patients, of which none have shown specific effectiveness in relapse prevention of alcohol dependents. We suggest the possibility that decreased 5-HT1A receptor sensitivity could be a predictive factor for poor clinical outcome, as the patients in our study were chronic patients with a history of multiple relapse who had abstained from alcohol for more than 3 months. To test this, however, comparison of alcoholic patients with persistently decreased 5-HT1A sensitivity with a sample of alcoholics with normalized 5-HT1A receptor sensitivity after the cessation of alcohol would need to be performed.
Our results should be interpreted with caution because of several limitations of our study. First, the effect of buspirone on the cortisol response may not directly reflect 5-HT1A receptor sensitivity. Second, we cannot exclude the possibility that blunted cortisol response to buspirone is due to hyporeactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Although many studies have reported that the chronic alcohol assumption can lead to disturbance of HPA axis and hormonal stress response (Nolan et al., 1991; Lee and Rivier, 1995
; Ehrenreich et al., 1997
), it is not a consistent finding. For example, Umhau et al. (2001)
reported that long-term abstinent alcoholics did not have an exaggerated corticotrophin and cortisol response after 2-deoxy-d-glucose (2-DG) compared to normal controls. Adinoff et al. (1990)
reported that corticotrophin response to Corticotropin releasing hormone (CRH) was significantly attenuated in the alcoholics within 3 weeks of abstinence, compared with controls; however, it was not significantly different after 3 weeks of abstinence. Moreover, in our study the baseline level of cortisol, which can be used as an index of the activity of the HPA-axis, was not significantly different between two groups. Thus we suggest our results may reflect the 5-HT1A dysfunction in the extended abstinent alcoholics. Third, our study was not a placebo-controlled neuroendocrine challenge. Fourth, serotonergic function in patients could be different according to their clinical characteristics, such as subtypes of alcoholism and comorbid psychopathology. In our study, we excluded any subjects with comorbid anxiety and depression or any other Axis I disorders, but not necessarily other symptoms such as aggression, and did not analyse separately cortisol response according to subtype of alcoholic. Also all subjects were male and fairly young, limiting the generalizability of our result. Also, the mean age of the alcoholic patients was higher than that of the controls, although age effect on cortisol response to buspirone was not found in our study, and it is not clearly determined yet whether the age influences cortisol response to buspirone.
Further work is needed to understand whether or not 5-HT1A receptor sensitivity changes are related to relapse in alcoholic patients. However, our results provide useful information and aid understanding of the role of the 5-HT1A receptor in the pathophysiology and clinical outcome of alcoholism.
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ACKNOWLEDGEMENTS |
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REFERENCES |
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