Early Life Stress in Adolescent Migraine and the Mediational Influence of Symptoms of Depression and Anxiety in a Canadian Cohort. 
This study sought to examine the association between early life stressors and adolescent headache in the Canadian population, and the potential mediating influence of symptoms of depression and anxiety.  Early life stress or adverse childhood experiences have a well-documented association with migraine and headache in adulthood, as do symptoms of depression and anxiety.  However, there is limited evidence examining the relationship between early life environmental stressors and adolescent headache, and a lack of longitudinal research.  Family-level factors including parenting behaviors and parental influences such as maternal distress have been implicated in pediatric chronic pain.  This study used data from 2313 respondents of the National Longitudinal Survey of Children and Youth, followed prospectively from age 0 to 1 years at baseline (1994/1995) until age 14 to 15 years (2008/2009).  The relationships between 4 measures of early life family level stressors, and outcomes of incident health professional-diagnosed migraine and self-reported, unclassified frequent headache (>1 per week) were examined.  We conducted a series of mediation analyses of the indirect effect (IE) of family-level stressors on headache outcomes through symptoms of depression and anxiety in late childhood.  The IE and 95% bias-corrected confidence interval (CIBC ) were estimated using maximum likelihood logistic regression methods (log odds scale).  The proportion of respondents with incident migraine and frequent headache was 3.1% and 11.1%, respectively.  There were no direct associations between distal early life family-level factors and adolescent headache.  Symptoms of depression- and anxiety-mediated relationships between family dysfunction (IE 0.0181, 95% CIBC 0.0001-0.0570), punitive parenting (IE 0.0241, 95% CIBC 0.0015-0.0633), parental depressive symptomatology (IE 0.0416, 95% CIBC 0.0017-0.0861), and incident migraine but not frequent headache.  Indirectly, presence of family dysfunction, punitive parenting, and higher parental depressive symptomatology in early life were associated with a greater likelihood of migraine in adolescence, through greater symptoms of depression and anxiety in late childhood.  Findings provide support for the influence of early life family-level factors on prospective risk of developing migraine, through symptoms of depression and anxiety.  Addressing family dynamics in clinical practice may reduce unnecessary stress-related burdens on children and adolescents, which could lead to improvements in their somatic complaints.