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These studies demonstrated significant methodological heterogeneity (i.e. age range, sex, presence of antidepressant use, method of depression measure, severity of depressive symptoms, duration and study design (RCT vs. cohort)).

The prevalence of comorbid depression varies considerably by method of depression assessment.

Meta-regression Because stratifying by (controlling for) method of depression measurement (diagnosis or questionnaire) reduced the significant overall study heterogeneity to non-significance, meta-regression analysis was performed to examine this further.

A priori meta-regression analysis was then performed to assess whether conclusions were sensitive to restricting studies to subgroups that might modify the effect size: i) mean age; ii) sex; iii) method of depression assessment; and iv) method of IR assessment.

In the included studies, method of depression assessment could be either 1) a diagnosis of depression assessed by a diagnostic psychiatric interview, 2) assessment of depressive symptoms by a self-report questionnaire, 3) a diagnosis by a physician, or 4) in combination with a prescription of antidepressant medication.

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However, the prevalence varied significantly by sex, study design, subject sources, and assessment methods of depression and MetS.

In general, the strength of the association between inflammation and major depression may vary depending on methods of depression diagnosis, sample characteristics, and control for confounders.

Heterogeneity between studies was not explained by age or sex, but could be partly explained by the methods of depression and IR assessments.

A series of random-effects subgroup analyses and meta-regression was conducted to examine whether the association between depression and IR varied across demographic groups and the methods of depression and IR assessments.

Using a standardized data extraction sheet, the following information (if available) was extracted and recorded from studies: authors; year of publication; country of origin; study design; total sample size of nondiabetic participants; age; sex; methods of IR assessment; methods of depression assessment; and type of confounders.

As Fig. 7 shows, methods of depressions filling, flow direction calculation, flow accumulation, and drainage network extraction are selected to compose the workflow.

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