Abstract

Introduction: Hypothyroidism is implicated in the pathophysiology and clinical course of mood disorders. This study aimed to investigate the association between TSH and severe depression.Methods: The historical cohort included all consecutive adult patients (≥ 18 years) who had a TSH and PHQ-9 questionnaire data within 6 months of index visit, between October 2016 and July 2019, at the University of Utah Health. Data on demographics, hypothyroidism, TSH, PHQ-9, thyroid hormone replacement (THR), and antidepressant medications were extracted electronically. T-test and chi-square were used to compare continuous and categorical variables respectively. Logistic regression and one-way ANOVA were used to evaluate the association between TSH and depression severity. A sub-group analysis was performed among mood disorder patients without a diagnosis of overt hypothyroidism, comparing euthyroid patients (TSH 0.3-4) and patients with sub-clinical hypothyroidism based on TSH 4-10.Results: The cohort included 26,722 patients, mean age 46.3 years, 79.5% Caucasian, 68% females, and mean BMI 30. Mean PHQ-9 score was 8.2, 10% patients had severe depression (PHQ-9 ≥20), and 51% were on antidepressants and 26% on mood stabilizers. Mean TSH was 2.85, 19% patients had a diagnosis of hypothyroidism, and 20% patients were on THR. Patients with severe depression were more likely to have a higher mean TSH (p=0.06), be on antidepressants (p= <0.0001), and have a higher BMI (p=0.0003). There was a positive correlation between TSH and PHQ-9 score (p= 0.04). TSH was associated with severe depression, odds ratio 1.006 (1.003-1.009), after adjusting for potential co-variates. Hypothyroid patients who were on THR had a lower mean PHQ-9 score (p= <0.0001) as compared to hypothyroid patients not on THR. Patients with TSH from 7-10 had a higher PHQ-9 score as compared to those who had a TSH from 4-7 (p= <0.003).Conclusion: Severe depression was associated with higher TSH. Subclinical hypothyroidism with TSH above 50th percentile was associated with higher PHQ-9 scores. Future RCTs should evaluate the effect of THR in (a) patients with severe depression and (b) patients with mood disorders who have subclinical hypothyroidism.

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