Suicide is the devastating result of complex interactions among multiple factors. To afflicted individuals, psychological pain becomes intolerable, and death seems to be the only option for escaping the pain. The specific biological changes in the brain that produce these overwhelming feelings are not completely understood. New evidence suggests that the immune system plays a significant role.

Clinical depression is the most common psychiatric disorder associated with completed suicides. It is likely that areas of the brain that are functioning abnormally in depression predispose a person to suicidal thinking.

Certain personality traits such as impulsivity may also increase the risk of suicide. This may be especially true in younger individuals. Environmental and social adversity may also contribute to suicidality.

Lena Brundin and colleagues recently published a paper in the journal Neuropsychopharmacology entitled “Role of Inflammation in Suicide: From Mechanism to Treatment.” As we discussed in our last post, the immune system is intimately involved in brain functioning. In their paper, Brundin and colleagues review a substantial amount of data demonstrating that immune mechanisms can contribute to suicidality.

This evidence is multifaceted. For instance, certain types of medications used to treat cancers by enhancing immune responses increase the risk of depression and suicidal thinking. Specific autoimmune disorders that attack the brain are also associated with increased suicidal behaviors. Multiple sclerosis and lupus are examples of such disorders. The immune system responds to fight infections, and certain brain infections are associated with increased suicidal behaviors. Traumatic brain disorders are also associated with inflammatory responses in the brain and can lead to behavioral changes including suicidal thinking.

Investigators have found that specific immune-related chemicals that mediate brain inflammatory responses are elevated in persons with suicidal behaviors. Similarly, levels of these chemicals have been shown to be increased in the brains of persons who died from suicide.

Certain medications diminish suicidal thoughts. For example, lithium, a drug helpful in treating bipolar disorder, diminishes the risk of suicide. One of lithium’s biochemical actions is to decrease levels of immune-related chemicals. A very different medication, ketamine, has recently been shown to rapidly diminish depressive symptoms and suicidal thoughts. Ketamine has several effects; one of these is the ability to block some of the chemicals involved in the immune response. 

Brundin and colleagues present cogent arguments that immune-related mechanisms can influence suicidal behaviors especially in the context of increased depressive thinking. Stimulating the production of pro-inflammatory chemicals in the brain is associated with increased depressive symptoms (particularly “sickness behaviors” such as dysphoria, sleep pattern changes, appetite changes, and fatigue among others) and suicidal thoughts. On the other hand, decreasing levels of immune chemicals in the brain may be associated with diminished depressive thinking and suicidal thoughts.

Does this mean that medications that block the action of certain immune-related chemicals could have anti-suicidal and anti-depressant properties? Such medications are currently at various stages of study. Results from such studies are encouraging but preliminary.

Suicidal behavior is a complex phenomenon and cannot be reduced to overly simplistic biochemical explanations. At the same time, it should be no surprise that certain chemical pathways in the brain are involved in this complex behavior. Medications that interact with these pathways may have the ability to reduce such behaviors and provide a person with the opportunity to more actively participate in therapy. Such a treatment strategy could have the potential to save lives.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.

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