Relationship between a GABA(A)α6 Pro385Ser substitution and benzodiazepine sensitivity

Nakao Iwata, Deborah S. Cowley, Marta Radel, Peter P. Roy-Byrne, David Goldman

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Objective: In humans, interindividual variation in sensitivity to benzodiazepine drugs may correlate with behavioral variation, including vulnerability to disease states such as alcoholism. In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)α6 receptor. The authors detected a Pro385Ser [1236C>T] amino acid substitution in the human GABA(A)α6 that may influence alcohol sensitivity. In this pilot study, they evaluated the contribution of this polymorphism to benzodiazepine sensitivity. Method: Sensitivity to diazepam was assessed in 51 children of alcoholics by using two eye movement measures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as dependent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro385 homozygotes. Results: The Pro385Ser genotype was associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain. Conclusions: The Pro385Ser genotype may play a role in benzodiazepine sensitivity and conditions, such as alcoholism, that may be correlated with this trait.

Original languageEnglish
Pages (from-to)1447-1449
Number of pages3
JournalAmerican Journal of Psychiatry
Volume156
Issue number9
Publication statusPublished - 01-09-1999

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Smooth Pursuit
Benzodiazepines
gamma-Aminobutyric Acid
Diazepam
Alcoholism
Genotype
Alcohols
Saccades
Homozygote
GABA-A Receptors
Amino Acid Substitution
Alcoholics
Heterozygote
Eye Movements
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

Cite this

Iwata, N., Cowley, D. S., Radel, M., Roy-Byrne, P. P., & Goldman, D. (1999). Relationship between a GABA(A)α6 Pro385Ser substitution and benzodiazepine sensitivity. American Journal of Psychiatry, 156(9), 1447-1449.
Iwata, Nakao ; Cowley, Deborah S. ; Radel, Marta ; Roy-Byrne, Peter P. ; Goldman, David. / Relationship between a GABA(A)α6 Pro385Ser substitution and benzodiazepine sensitivity. In: American Journal of Psychiatry. 1999 ; Vol. 156, No. 9. pp. 1447-1449.
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Iwata, N, Cowley, DS, Radel, M, Roy-Byrne, PP & Goldman, D 1999, 'Relationship between a GABA(A)α6 Pro385Ser substitution and benzodiazepine sensitivity', American Journal of Psychiatry, vol. 156, no. 9, pp. 1447-1449.

Relationship between a GABA(A)α6 Pro385Ser substitution and benzodiazepine sensitivity. / Iwata, Nakao; Cowley, Deborah S.; Radel, Marta; Roy-Byrne, Peter P.; Goldman, David.

In: American Journal of Psychiatry, Vol. 156, No. 9, 01.09.1999, p. 1447-1449.

Research output: Contribution to journalArticle

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N2 - Objective: In humans, interindividual variation in sensitivity to benzodiazepine drugs may correlate with behavioral variation, including vulnerability to disease states such as alcoholism. In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)α6 receptor. The authors detected a Pro385Ser [1236C>T] amino acid substitution in the human GABA(A)α6 that may influence alcohol sensitivity. In this pilot study, they evaluated the contribution of this polymorphism to benzodiazepine sensitivity. Method: Sensitivity to diazepam was assessed in 51 children of alcoholics by using two eye movement measures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as dependent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro385 homozygotes. Results: The Pro385Ser genotype was associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain. Conclusions: The Pro385Ser genotype may play a role in benzodiazepine sensitivity and conditions, such as alcoholism, that may be correlated with this trait.

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