The study showed that girls who had early conduct problems in elementary school also were at an increased risk for depression in early adulthood.
However, it did not show any link for boys between academic, behaviour or social problems and depression at age 21.
"For girls there are broader implications of school failure. We already know that it leads to more poverty, higher rates of being on public assistance and lower rates of job stability. And now this study shows it is having mental health implications for girls," said Carolyn McCarty, a UW research associate professor of paediatrics and lead author of the study.
During the study, researchers found that girls who were expelled from school were more than twice as likely to suffer depression - 44 percent compared to 20 percent of girls who were not expelled.
They found that 33 percent of the girls who dropped out of school later became depressed compared to 19 percent who were not dropouts.
The study also showed that 28 percent of the girls who were suspended later suffered depression versus 19 percent of girls who weren't suspended.
Overall, 45 percent of the girls and 68 percent of the boys in the study experienced a major school failure, but McCarty said these rates were not surprising since the participants in the study came from high-crime neighbourhoods.
However, the depression rate was higher among girls, 22 percent versus 17 percent for the boys.
"This gender paradox shows that while school failure is more atypical for girls it appears to have more severe consequences when it does occur," McCarty said
"One reason may be that school failure stigmatizes girls more strongly or is harder for them to overcome. We do know that girls with conduct problems, such as school failure, tend to have long-term problems with cascading effects," McCarty added.
The study is published this week in the Journal of Adolescent Health.