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).


CONCLUSIONS
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.
Cooper-Kazaz
Rena
R
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
van der Deure
Wendy M
WM
Medici
Marco
M
Visser
Theo J
TJ
Alkelai
Ana
A
Glaser
Benjamin
B
Peeters
Robin P
RP
Lerer
Bernard
B
D000928:Antidepressive Agents / Q000627:therapeutic use*; D004247:DNA; D003866:Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D004359:Drug Therapy, Combination; D005838:Genotype; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D020280:Sertraline / Q000627:therapeutic use*; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000378:metabolism; D014284:Triiodothyronine / Q000627:therapeutic use*; D000097564:Iodothyronine Deiodinase Type II
D000928:Antidepressive Agents; D004247:DNA; D007453:Iodide Peroxidase; D020280:Sertraline; D013972:Thyrotropin; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I