Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies
Lamprini Syrogiannouli,
Stephan J L Bakker,
Rudi G J Westendorp,
Luigi Ferrucci,
Elisavet Moutzouri,
Martin Feller,
Drahomir Aujesky,
Nicolas Rodondi,
Henry Völzke,
Hans Grabe,
Jacobijn Gussekloo,
Matthias Nauck,
Cinzia Del Giovane,
J Wouter Jukema,
Lea Wildisen,
Shanthi Beglinger,
Anne R Cappola,
Bjørn O Åsvold,
Graziano Ceresini,
Robin Dullaart,
Stella Trompet,
Robin P Peeters,
Stefan Klöppel,
Douglas C Bauer
Affiliations
Lamprini Syrogiannouli
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
Stephan J L Bakker
2 University Medical Centre, Groningen, Netherlands
Rudi G J Westendorp
1 Public Health, University of Copenhagen, Copenhagen, Denmark
Luigi Ferrucci
2 Translational Gerontology Branch Longitudinal Studies Section, National Institute on Aging, Bethesda, Maryland, USA
Elisavet Moutzouri
6 Department of General Internal Medicine and Institute of Primary Health Care (BIHAM), Inselspital Bern, University of Bern, Bern, Switzerland
Martin Feller
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
Drahomir Aujesky
1 Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Nicolas Rodondi
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Henry Völzke
Institute for Community Medicine, Clinical-Epidemiological Research, University Medicine Greifswald, Greifswald, Germany
Hans Grabe
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
Jacobijn Gussekloo
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, South-Holland, Netherlands
Matthias Nauck
DZHK, German Centre for Cardiovascular Research, Partner Site Greifswald, University Medicine, Greifswald, Germany
Cinzia Del Giovane
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
J Wouter Jukema
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Lea Wildisen
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
Shanthi Beglinger
research fellow
Anne R Cappola
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
Bjørn O Åsvold
Department of Public Health and Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Graziano Ceresini
Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy
Robin Dullaart
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Stella Trompet
2Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
Robin P Peeters
Department of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Stefan Klöppel
University Hospital of Old Age Psychatry, University of Bern, Bern, Switzerland
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.
