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Background Depressive disorders are frequently under diagnosed in resource-limited settings because of lack of access to mental health care or the inability of healthcare providers to recognize them. The Patient Health Questionnaire (PHQ)-2 and the PHQ-9 have been widely used for screening and diagnosis of depression in primary care settings; however, the validity of their use in rural, Spanish-speaking populations is unknown. Method We used a cross-sectional design to assess the psychometric properties of the PHQ-9 for depression diagnosis and estimated the sensitivity and specificity of the PHQ-2 for depression screening. Data were collected from 223 adults in a rural community of Chiapas, Mexico, using the PHQ-2, the PHQ-9, and the World Health Organization Quality of Life BREF Scale (WHOQOL- BREF). Results Confirmatory factor analysis suggested that the 1-factor structure fit reasonably well. The internal consistency of the PHQ-9 was good (Cronbach's alpha > = 0.8) overall and for subgroups defined by gender, literacy, and age. The PHQ-9 demonstrated good predictive validity: Participants with a PHQ-9 diagnosis of depression had lower quality of life scores on the overall WHOQOL-BREF Scale and each of its domains. Using the PHQ-9 results as a gold standard, the optimal PHQ-2 cutoff score for screening of depression was 3 (sensitivity 80.00%, specificity 86.88%, area under receiver operating characteristic curve = 0.89; 95% confidence interval [0.84, 0.94]). Conclusion The PHQ-2 and PHQ-9 demonstrated good psychometric properties, suggesting their potential benefit as tools for depression screening and diagnosis in rural, Spanish-speaking populations. [ABSTRACT FROM AUTHOR]