Precipitants of adolescent suicide: possible interaction between allergic inflammation and alcohol intake

Suicide is a leading cause of mortality among adolescents. There is a pressing public health need to investigate triggers and novel vulnerabilities for suicide in order to improve risk assessment and develop innovative prevention strategies. Alcohol is a well established risk factor for adolescent suicide. In this paper, we outline a novel mechanism linking allergy, alcohol, and suicide, reviewing (a) the association between allergic inflammation, depression, and suicide; and (b) the role of alcohol in inducing phosphorylation and rearrangement of tight junction proteins of the blood-brain barrier (BBB) resulting in increased "leakiness", i.e. passage of cells and molecules. Seasonal peaks of suicide in spring have been consistently reported, but their causality is poorly understood. A preliminary epidemiologic study found increased nonviolent suicide rates in females in spring during intervals of high tree pollen, in comparison to similar intervals of low tree pollen. This initial report added to the emerging literature proposing a relationship between allergy and depression, and is being further pursued at clinical, epidemiological, animal and postmortem tissue levels. We propose that allergic inflammation influences depression-related brain function via molecular and cellular mediators, but those mediators have a very limited access to the brain when the BBB is intact. Alcohol intake disrupts BBB, allowing increased brain exposure to cellular mediators of allergy. Considering the greater prevalence of allergy in adolescence when alcohol use starts, studies investigating the connection between allergy, alcohol, and suicide should be expanded to also include a focus on youth.