"Major depressive disorder is thought to result from the complex interplay of multiple inherited factors and subsequent exposure to a wide range of environmental variables through life," write Dr. Mathew and coauthors.

The review provides a framework for this complex disease that requires a diverse approach in research, diagnosis and treatment. Current treatment options are limited by their delayed onset of action, lack of efficacy and adverse outcomes.

The authors conclude that "much needs to be explored in terms of how genes interact with other environmental variables to influence the risk of major depressive disorder."


Having a mental illness alone at the first interview did not predict whether an individual would have violent behavior before the second interview. However, individuals with both mental illness and substance abuse or dependence were at higher risk for future violence. "The highest risk was shown for dual-disordered subjects with a history of violence, who showed nearly 10 times higher risk of violence compared with subjects with severe mental illness only," the authors write.

Other factors that predicted future violence included a history of juvenile detention, physical abuse or having witnessed parental fighting; a recent divorce, unemployment or victimization; or being younger, male or lower-income. Most of these risk factors were present more often in individuals with mental illness.

"Because severe mental illness did not independently predict future violent behavior, these findings challenge perceptions that mental illness is a leading cause of violence in the general population," the authors conclude. "Still, people with mental illness did report violence more often, largely because they showed other factors associated with violence. Consequently, understanding the link between violent acts and mental disorder requires consideration of its association with other variables such as substance abuse, environmental stressors and history of violence."