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Saturday, March 1, 2008

Citalopram Neuropharmacological Challenge in Alcohol-Dependent Patients and Controls: Pharmacogenetic, Endocrine and Psychobehavioral Results
Pharmacopsychiatry 2008; 41: 72-78

Alcoholism has been associated with long-lasting alterations in LHPA (limbic-hypothalamus-pituitary-adrenal) axis function, related to a dysfunction of the serotonergic neurotransmission. Functional polymorphisms of the serotonin system were previously reported to have significant influence on serotonin-induced neuroendocrine response.

The aim of the study is to investigate in a double-blind, placebo-controlled approach, whether citalopram (a selective serotonin reuptake inhibitor, SSRI) would affect LHPA axis function as measured with ACTH (adrenocorticotrophic hormone) levels representing endocrine responsivity in 11 alcohol-dependent individuals compared to 12 controls.

Furthermore we wanted to know whether functional polymorphisms (5-HTTLPR and 5HT2C Ser23Cys), have any influence on this responsivity.

ACTH levels were higher for both groups in the verum compared to placebo administrations across timepoints. 5HT2C Ser23 alleles effected significantly higher ACTH responses under placebo administration but attenuated the responses under citalopram adminsitration. Considering both groups together, no influence of 5-HTTLPR alleles was found on ACTH levels in either group under either regimen. While citalopram adminsitration did not reduce craving in alcohol-dependent patients, it increased anxiety in patients and controls compared to placebo adminstration.

Despite the small differences in endocrine and subjective responses between alcoholic patients and controls, the effect of SSRI on endocrine response with respect to 5HT2C functional alleles deserves further investigation in larger samples to clarify whether this genetic variant constitutes a potential risk factor for changes in neuroendocrine functioning and subsequent psychiatric disorders.

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