Iron Deficiency and Internalizing Symptoms Among Adolescents in the National Health and Nutrition Examination Survey

Abstract

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans. Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association between ID status (defined based on the total body iron model) and (1) total Patient Health Questionnaire (PHQ-9) score, (2) one item examining anxiety severity, and (3) one item examining overall mental well-being. Covariates included age, sex, race and ethnicity, body mass index, household income, head-of-household marital status, and psychotropic medication use. Sensitivity analyses examined the robustness of the findings when ID was defined based on the ferritin model. Results: In 1990 adolescents (age [mean ± SD]: 14.5 ± 1.7 years; 85.7% females), ID with and without anemia was significantly associated with a higher PHQ-9 score in multiracial adolescents (Cohen’s d = 1.09, p = 0.0005 for ID without anemia; d = 0.92, p = 0.0395 for ID with anemia). Moreover, ID with anemia was associated with more severe anxiety (d = 3.00, p = 0.0130) and worse mental well-being (d = 2.75, p = 0.0059) in multiracial adolescents. The findings remained significant after adjusting for psychotropic use and in the sensitivity analyses. Conclusions: Iron deficiency is associated with poorer mental health in adolescents of multiracial background. Future studies should confirm these findings prospectively and examine the underlying mechanism.