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Background  Compared to general children, orphans and vulnerable children (OVC) are more exposed to negative outcomes in life such as abuse and neglect. Consequently, OVC are more susceptible to depression. This paper investigated factors associated with depressive symptoms among OVC in Cambodia.    Methods  In this cross-sectional study, data of 606 OVC from the Sustainable Action against HIV and AIDS in Communities (SAHACOM) project were analyzed. The data were collected from five provinces and analyzed separately for boys and girls. Multiple linear regression analysis was used to identify factors independently associated with levels of depressive symptoms.    Results  Both boys and girls who reported having been too sick making them unable to attend school or go to work in the past six months (boys: B = 3.5; 95 % CI = 0.7, 6.2; girls: B = 5.7; 95 % CI = 2.9, 8.5) and who had witnessed violence in the family (boys: B = 5.6; 95 % CI = 1.6, 9.6; girls: B = 5.8; 95 % CI = 1.7, 9.9) had a higher level of depressive symptoms. Girls who were older (B = 8.5; 95 % CI = 3.0, 14.0), who did not have enough food in the past six months (B = −8.7; 95 % CI = −13.7, −3.7) and whose parents were separated, divorced or dead (B = 3.9; 95 % CI = 0.5, 7.2) had a higher level of depressive symptoms. Higher level of school attachment was negatively associated with depressive symptoms in both genders (boys: B = −1.4; 95 % CI = −2.0, −0.9; girls: B = −1.4; 95 % CI = −2.0,-0.9).    Conclusions  Factors such as physical health and exposure to violence may affect mental health of OVC in Cambodia. As health is of utmost importance, better healthcare services should be made easily accessible for OVC. Schools have the potential to act as a buffer against depressive symptoms. Therefore, efforts should be made to keep OVC in school and to improve the roles of school in Cambodia.

What are the factors associated with depressive symptoms among orphans and vulnerable children in Cambodia?