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

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.

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