REVIEW OF: Bode H et al, JAMA Psychiatry 2021;78(12):1375–1383

STUDY TYPE: Meta-analysis of epidemiologic and population-based studies

Hypothyroidism and depression are related, right? Actually, the connection is not so clear. Prior studies have supported a connection, but they had limitations, such as small sample sizes, patients with severe disease, and rating scale cutoffs that were not clinically relevant. In the current meta-analysis, a group of psychiatrists led by Henry Bode attempted to clarify the link between these conditions.

Investigators screened databases for epidemiologic and population-based studies with laboratory and diagnostic evidence of hypothyroidism and major depression, as defined by DSM or ICD criteria. Of the 4,350 studies screened, 25 passed muster according to the Newcastle-Ottawa Scale, a standardized quality assessment of nonrandomized studies.

In total, the analysis included 348,014 patients, of which 53.6% were female and the mean age was 45 years (range 18–91). The primary outcome was the association between depression and hypothyroidism or thyroid autoimmunity. Secondary outcomes included the impact of subclinical vs overt hypothyroidism, gender, and age.

Hypothyroidism and depression were associated, but much less than expected (odds ratio [OR] of 1.3, indicating a 30% increased risk, with a range [95% CI] of 1.08–1.57). The association was stronger for clinical hypothyroidism (OR 1.77; 95% CI 1.13–2.77) than subclinical (OR 1.13; 95% CI 1.01–1.28), which suggests a dose effect with the degree of hypothalamic-pituitary-thyroid axis disturbance. On the other hand, thyroid autoimmunity and depression were not associated (OR 1.24; 95% CI 0.89–1.74), indicating that the immune system is not involved. Age did not affect the outcome, but the association between hypothyroidism and depression was stronger for women than men.

One limitation of this meta-analysis is that the analyzed studies had varying methodologies, but the results did not change when those variations were removed in a subanalysis. Strengths of this meta-analysis include that it focused on patients from the general population; also, the study was funded by an independent university grant that did not introduce any apparent bias.

CARLAT TAKE

Few things in psychiatry are black and white, and this study moves the hypothyroidism-depression link into the gray area, particularly with subclinical cases. The results do not negate the importance of considering hypothyroidism, however, as we may still see depression develop in patients with overt disease, meaning clear physical symptoms of low thyroid in addition to lab evidence.