Thyrotropin, but not a polymorphism in type II deiodinase, predicts response to paroxetine in major depression

Abstract

Objective: The determinants of response to antidepressant treatment in major depression are unknown at present. The aim of the present study was to establish whether response is predicted by Hypothalamus-Pituitary-Thyroid (HPT) axis parameters or by a recently discovered polymorphism in the enzyme type II deiodinase (DII), which catalyzes the production of T 3 in the brain. Design: We analyzed prediction of response to paroxetine treatment by calculating response rates per tertile of HPT-axis parameters and per DII genotype. Methods: Ninety-eight outpatients with major depression (DSM-IV) were included. Serum concentrations of TSH, FT 4 and delta TSH in a DEX/CRH-TRH test were measured. In addition, the presence of a polymorphism in the DII sequence (Thr92Ala) was determined. Results: The overall treatment response was 48 of 98 patients (49%). After exclusion of patients with subclinical hypothyroidism and/or TPO antibodies (nZ16), higher serum TSH significantly predicted response (response rate per tertile from low to high TSH: 36%, 42%, and 67%). Heterozygous patients for the DII polymorphism (44%) had slightly lower serum TSH (PZ0.03) as compared to patients with the wild-type DII (47%). The polymorphism was unrelated to treatment response. Conclusion: Higher serum TSH was associated with response to paroxetine in patients with major depression.European Journal of Endocrinology 154 819-825

Combined Treatment With Sertraline and Liothyronine in Major Depression

“…An alternative explanation, that relatively low T 3 levels may be caused by genetic variants in any of the 3 deiodinase genes, is intriguing. One recent study did not find an association between a polymorphism in type II deiodinase and response to paroxetine hydrochloride, 34 but further studies are needed to explore this issue.…”

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders

“…For example, a study investigating pituitary secreted hormones into the bloodstream, revealed that higher serum TSH significantly predicted response to paroxetine (Brouwer et al, 2006). Higher plasma fibrinogen levels were identified in non-responders compared to responders to mixed antidepressants (Martins-de-Souza et al, 2014).…”

GENETICS IN ENDOCRINOLOGY: Genetic variation in deiodinases: a systematic review of potential clinical effects in humans

“…Other D1 and D2 polymorphisms (D1-A1814G, D2-ORF a -Gly3Asp, and D2-Thr92Ala) did not show a relationship with therapeutic response in this study. Brouwer et al (45) reported that the Thr92Ala polymorphism was not associated with response rate to antidepressant therapy with paroxetine in 96 patients treated for major depression.…”