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An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

ABSTRACT: In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (±?4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference?=?0.29, 95% confidence interval?=??-?0.17 to 0.76, I2?=?15.6) or subclinical hyperthyroidism (-?0.10, 95% confidence interval?=??-?0.67 to 0.48, I2?=?3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

SUBMITTER: Wildisen L

PROVIDER: S-EPMC7644764 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

Wildisen Lea L Del Giovane Cinzia C Moutzouri Elisavet E Beglinger Shanthi S Syrogiannouli Lamprini L Collet Tinh-Hai TH Cappola Anne R AR Åsvold Bjørn O BO Bakker Stephan J L SJL Yeap Bu B BB Almeida Osvaldo P OP Ceresini Graziano G Dullaart Robin P F RPF Ferrucci Luigi L Grabe Hans H Jukema J Wouter JW Nauck Matthias M Trompet Stella S Völzke Henry H Westendorp Rudi R Gussekloo Jacobijn J Klöppel Stefan S Aujesky Drahomir D Bauer Douglas D Peeters Robin R Feller Martin M Rodondi Nicolas N

Scientific reports 20201105 1

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and A ...[more]

PMID: 33154486

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Project description:IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.Prospero registration numberCRD42018091627.

Project description:ImportanceIn clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.ObjectiveTo assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.Design, setting, and participantsThis multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.ExposuresThyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values.Main outcomes and measuresThe primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated.ResultsAmong 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia.Conclusions and relevanceIn this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

Project description:AimsTo investigate cross-sectional and longitudinal associations between personality and smoking, and test whether socio-demographic factors modify these associations.DesignCross-sectional and longitudinal individual-participant meta-analysis.SettingNine cohort studies from Australia, Germany, the United Kingdom and the United States.ParticipantsA total of 79 757 men and women (mean age = 50.8 years).MeasurementsPersonality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness and openness to experience) were used as exposures. Outcomes were current smoking status (current smoker, ex-smoker and never smoker), smoking initiation, smoking relapse and smoking cessation. Associations between personality and smoking were modelled using logistic and multinomial logistic regression, and study-specific findings were combined using random-effect meta-analysis.FindingsCurrent smoking was associated with higher extraversion [odds ratio per 1 standard deviation increase in the score: 1.16; 95% confidence interval (CI) = 1.08-1.24], higher neuroticism (1.19; 95% CI = 1.13-1.26) and lower conscientiousness (95% CI = 0.88; 0.83-0.94). Among non-smokers, smoking initiation during the follow-up period was predicted prospectively by higher extraversion (1.22; 95% CI = 1.04-1.43) and lower conscientiousness (0.80; 95% CI = 0.68-0.93), whereas higher neuroticism (1.16; 95% CI = 1.04-1.30) predicted smoking relapse among ex-smokers. Among smokers, smoking cessation was negatively associated with neuroticism (0.91; 95% CI = 0.87-0.96). Socio-demographic variables did not appear to modify the associations between personality and smoking.ConclusionsAdult smokers have higher extraversion, higher neuroticism and lower conscientiousness personality scores than non-smokers. Initiation into smoking is associated positively with higher extraversion and lower conscientiousness, while relapse to smoking among ex-smokers is associated with higher neuroticism.

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An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

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An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

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