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 T3 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, FT4 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 (n = 
16), 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 (P = 0.03) 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.