Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based Cohort Study

Medici, Marco; Direk, Neşe; Visser, W. Edward; Korevaar, Tim I M; Hofman, Albert; Visser, Theo J.; Tiemeier, Henning; Peeters, Robin P.

doi:10.1210/jc.2013-3589

Cited by 97 publications

(71 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In euthyroid subjects without thyroid disease, depression, anxiety, or cognitive decrements have been linked to variations in TSH or free thyroxine (fT4) levels (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, the correlations have shown improvements or decrements with higher or lower thyroid function, depending on the report.…”

Section: Introductionmentioning

confidence: 99%

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

Samuels

Kolobova

Smeraglio

et al. 2016

Thyroid

View full text Add to dashboard Cite

Background: There has been recent debate within the thyroid field regarding whether current upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. One important target organ for thyroid hormone is the brain, but little is known about variations in neurocognitive measures within the reference range for thyroid function.Methods: This was a cross-sectional study of 132 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (LT4) who had TSH levels across the full span of the laboratory reference range (0.34-5.6 mU/L). Subjects underwent detailed tests of health status, mood, and cognitive function, with an emphasis on memory and executive functions. Results: Subjects with low-normal (£2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ on most tests of health status, mood, or cognitive function, and there were no correlations between TSH, free T4, or free T3 levels and most outcomes. There was, however, a suggestion that thyroid function affected performance on the Iowa Gambling Task, which mimics real life decision-making. Subjects with low-normal TSH levels made more advantageous decisions than those with high-normal TSH levels. Conclusions: Variations in thyroid function within the laboratory reference range do not appear to have clinically relevant effects on health status, mood, or memory in LT4 treated subjects. However, decision making, which encompasses many executive functions, may be affected. Unless further studies strengthen this finding, these data do not support narrowing the TSH reference range.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

Samuels

Kolobova

Smeraglio

et al. 2016

Thyroid

View full text Add to dashboard Cite

show abstract

“…FT4 levels within the normal range in a few cross-sectional studies (13,14,16). However, the correlations were in different directions depending on the report, and recent large and wellconducted studies found no correlations between TSH levels and depression or anxiety (20,22,24).…”

Section: Discussionmentioning

confidence: 95%

“…To our knowledge, no prospective studies have examined the effects of variations in thyroid function within the reference range on quality of life over time. A few prospective studies have correlated baseline thyroid function within the reference range with the development of depressive symptoms (16,20,22). Two of these studies failed to find an association (20,22), while the third reported that lower TSH levels within the reference range were associated with more depressive symptoms and incident diagnoses of clinical depression (16).…”

Section: Discussionmentioning

confidence: 99%

“…A few prospective studies have correlated baseline thyroid function within the reference range with the development of depressive symptoms (16,20,22). Two of these studies failed to find an association (20,22), while the third reported that lower TSH levels within the reference range were associated with more depressive symptoms and incident diagnoses of clinical depression (16). Similarly, a few studies have examined possible correlations between baseline thyroid function in the euthyroid range and cognitive performance over time (11,17,19,20,23).…”

Section: Discussionmentioning

confidence: 99%

“…In healthy euthyroid subjects without known thyroid disease and who are not receiving thyroid hormone therapy, depression, anxiety, or cognitive decrements have been linked to variations in TSH, free T4, or free T3 levels (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). However, when correlations were found, they were in different directions depending on the report.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men

Samuels

Kaimal

Waring

et al. 2016

Thyroid

View full text Add to dashboard Cite

Background: Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes. Methods: Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of communitydwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates. Results: At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis. Conclusions: Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

show abstract

Association of Hypothyroidism and Clinical Depression

et al. 2021

View full text Add to dashboard Cite

IMPORTANCE Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of the association. It is also unclear whether the link is largely due to subsyndromal depression or holds true for clinical depression.OBJECTIVE To estimate the association of hypothyroidism and clinical depression in the general population.DATA SOURCES PubMed, PsycINFO, and Embase databases were searched from inception until May 2020 for studies on the association of hypothyroidism and clinical depression. STUDY SELECTION Two reviewers independently selected epidemiologic and population-based studies that provided laboratory or International Statistical Classification of Diseases and Related Health Problems diagnoses of hypothyroidism and diagnoses of depression according to operationalized criteria (eg, Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases and Related Health Problems) or cutoffs in established rating scales.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data and evaluated studies based on the Newcastle-Ottawa Scale. Summary odds ratios (OR) were calculated in random-effects meta-analyses.MAIN OUTCOMES AND MEASURES Prespecified coprimary outcomes were the association of clinical depression with either hypothyroidism or autoimmunity. RESULTSOf 4350 articles screened, 25 studies were selected for meta-analysis, including 348 014 participants. Hypothyroidism and clinical depression were associated (OR, 1.30 [95% CI, 1.08-1.57]), while the OR for autoimmunity was inconclusive (1.24 [95% CI, 0.89-1.74]). Subgroup analyses revealed a stronger association with overt than with subclinical hypothyroidism, with ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28), respectively. Sensitivity analyses resulted in more conservative estimates. In a post hoc analysis, the association was confirmed in female individuals (OR, 1.48 [95% CI,) but not in male individuals (OR, 0.71 [95% CI, 0.40-1.25]). CONCLUSIONS AND RELEVANCEIn this systematic review and meta-analysis, the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. Autoimmunity alone may not be the driving factor in this comorbidity.

show abstract

Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based Cohort Study

Abstract: Elderly persons with low-normal TSH levels have more concurrent depressive symptoms as well as a substantially increased risk of developing a depressive syndrome in the subsequent years. This study identifies low-normal TSH as an important risk factor for depression in the elderly.

Cited by 97 publications

References 36 publications

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men

Association of Hypothyroidism and Clinical Depression

Contact Info

Product

Resources

About