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Background: Metabolic risk factors, low cognitive function and history of depression are known risk factors for future depressive episodes. This paper aims to evaluate the potential interactions between these factors on the risk of a major depressive episodes in middle-age.Methods: Baseline and follow-up data from a population-based study of Quebec, Canada were used. The sample consisted of 1788 adults between 40 and 69 years of age without diabetes. Cognitive function and metabolic risk factors were assessed at baseline. Three cognitive domains were assessed: processing speed, episodic memory and executive function. History of depression was assessed five years later by a clinical interview. Logistic regression analysis was conducted to evaluate interactions between individual metabolic factors, low cognitive function, and depression history.Results: Participants with a comorbidity of at least one metabolic factor, history of depression and low cognitive function had the highest risk of experiencing a depressive episode in middle age. The highest risk was observed in individuals with abdominal obesity, low cognitive function, and a history of depression (OR= 8.66, 95% CI 3.83-19.59). The risks for those with abdominal obesity only, depression history only, and low cognitive function were 1.20 (95%CI 0.71-2.02), 3.10 (95%CI 1.81-5.24), and 1.39 (95%CI 0.72-2.67), respectively.Limitations: Depression was only assessed at follow-up.Conclusion: Metabolic risk factors comorbid with low cognitive function in middle-aged individuals with a history of depression were associated with an increased risk of a future depressive episode. This study highlights the importance of screening for metabolic and cognitive comorbidities in patients with a history of depression. [ABSTRACT FROM AUTHOR]