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Temporal Relations Between Unexplained Fatigue and Depression: Longitudinal Data From an International Study in Primary Care

From the Department of Psychiatry (P.S., V.M.), University of Ioannina, School of Medicine, Greece; and the Department of Psychiatry (P.S., G.L.), University of Bristol, UK.

Address correspondence and reprint requests to Dr. Petros Skapinakis, Department of Psychiatry, University of Ioannina School of Medicine, Ioannina 45110, Greece. E-mail: pskapin{at}cc.uoi.gr

OBJECTIVE: Unexplained fatigue syndromes, such as chronic fatigue syndrome and neurasthenia, are strongly associated with depression, but the temporal nature of this association is not clear.

METHODS: The authors examined this issue by using data from the World Health Organization collaborative study of psychological problems in general health care. Three thousand two hundred one subjects from 15 primary care centers in 14 countries were followed up for 12 months. The Composite International Diagnostic Interview was the main instrument used. Odds ratios and their 95% confidence intervals (CI) were calculated using logistic regression models adjusted for sociodemographic variables, physical morbidity and intercenter variability.

RESULTS: Cases of depression were found to have an increased risk of developing a new episode of unexplained fatigue at follow-up with an adjusted odds ratio of 4.15 (95% CI = 2.64–6.54). Similarly, cases of unexplained fatigue were found to have an increased risk of developing a new episode of depression at follow-up with an adjusted odds ratio of 2.76 (95% CI = 1.32–5.78). Further adjustment for subthreshold symptoms at baseline weakened the reported associations, especially between fatigue and development of a new episode of depression, but these remained significant.

CONCLUSIONS: The findings support the view that unexplained fatigue and depression might act as independent risk factors for each other.

Key Words: comorbidity, • depressive disorder, • fatigue syndrome, • chronic, • follow-up studies, • primary health care.

Abbreviations: CI = confidence interval;; CIDI = Composite International Diagnostic Interview;; GHQ-12 = 12-Item General Health Questionnaire;; GHQ-28 = 28-Item General Health Questionnaire;; GNI = gross national income;; ICD-10 = International Classification of Diseases, Tenth Revision;; WHO = World Health Organization.

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