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J Affect Disord. 2009 Jul;116(1-2):113-6. doi: 10.1016/j.jad.2008.10.019. Epub 2008 Dec 6.

Preliminary evidence that a functional polymorphism in type 1 deiodinase is associated with enhanced potentiation of the antidepressant effect of sertraline by triiodothyronine.

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1
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract

BACKGROUND:

Triiodothyronine (T3) is used to potentiate the clinical effect of antidepressant drugs. Inter-individual differences in efficacy may be related to genetically-based variability in thyroid function.

METHODS:

DNA was obtained from 64 patients treated with sertraline plus T3 (SERT-T3, N=35) or plus placebo (SERT-PLB, N=29), for 8 weeks. Antidepressant efficacy was rated with the 21 item Hamilton Rating Scale for Depression (HRSD-21). Functional polymorphisms in type 1 (DIO1-C785T, DIO1-A1814G) and type 2 deiodinase (DIO2-Thr92Ala and DIO2-ORFa-Gly3Asp) were genotyped.

RESULTS:

DIO1-C785T was associated with efficacy of T3 but not placebo supplementation, as indicated by the interaction of treatment, DIO1-C758T genotype and time (p=0.04) and a stronger effect of SERT-T3 among DIO1-758T allele carriers (p=0.01). HRSD-21 scores of DIO1-758T allele carriers declined by 68.7+26.6% (mean+SD) over 8 weeks compared to 42.9+37.8% among non-carriers (p=0.02).

DISCUSSION:

DIO1 plays a key-role in T4 to T3 conversion and in clearance of the inactive metabolite, rT3. Previous data associate the DIO1-785T allele with lower DIO1 activity. This is consistent with our observation that responders to T3 supplementation had lower baseline serum T3 levels than non-responders. Depressed patients, who have a genetically determined lower T4 to T3 conversion, may be more likely to benefit from T3 supplementation.

PMID:
19064291
DOI:
10.1016/j.jad.2008.10.019
[Indexed for MEDLINE]
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