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BMJ Open. 2019 Jul 26;9(7):e029716. doi: 10.1136/bmjopen-2019-029716.

Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies.

Author information

1
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
2
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
3
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
4
Department of Public Health and Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
5
Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
6
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
7
Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy.
8
Longitudinal Studies Section, Translational Gerontology Branch, Harbor Hospital, Baltimore, National Institute on Aging NIA-ASTRA Unit, Baltimore, Maryland, USA.
9
Institute for Community Medicine, Clinical-Epidemiological Research, University Medicine Greifswald, Greifswald, Germany.
10
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
11
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
12
DZHK, German Centre for Cardiovascular Research, Partner Site Greifswald, University Medicine, Greifswald, Germany.
13
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
14
Department of Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
15
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
16
Department of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
17
University Hospital of Old Age Psychatry, University of Bern, Bern, Switzerland.
18
Departments of Medicine and Epidemiology & Biostatistics, University of California, San Francisco, California, USA.

Abstract

INTRODUCTION:

Prospective 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 ANALYSIS:

We 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 DISSEMINATION:

Formal 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 NUMBER:

CRD42018091627.

KEYWORDS:

depressive symptoms; individual participant data (IPD) meta-analysis; subclinical hyperthyroidism; subclinical hypothyroidism; subclinical thyroid dysfunction; systematic review

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