TY - JOUR

T1 - Macrophage migration inhibitory factor (MIF) gene is associated with adolescents’ cortisol reactivity and anxiety

AU - Lipschutz, Rebecca

AU - Bick, Johanna

AU - Nguyen, Victoria

AU - Lee, Maria

AU - Leng, Lin

AU - Grigorenko, Elena

AU - Bucala, Richard

AU - Mayes, Linda C.

AU - Crowley, Michael J.

PY - 2018/9

Y1 - 2018/9

N2 - Emerging evidence points to interactions between inflammatory markers and stress reactivity in predicting mental health risk, but underlying mechanisms are not well understood. Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine involved in inflammatory signaling and Hypothalamus Pituitary Adrenal (HPA) axis stress-response, and has recently been identified as a candidate biomarker for depression and anxiety risk. We examined polymorphic variations of the MIF gene in association with baseline MIF levels, HPA axis reactivity, and self-reported anxiety responses to a social stressor in 74 adolescents, ages 10–14 years. Genotyping was performed for two polymorphisms, the -794 CATT5-8 tetranucleotide repeat and the -173*G/C single nucleotide polymorphism (SNP). Youth carrying the MIF-173*C and CATT7 alleles displayed attenuated cortisol reactivity when compared with non-carriers. Children with the CATT7-173*C haplotype displayed lower cortisol reactivity to the stressor compared to those without this haplotype. Additionally, the CATT5-173*C and CATT6-173*C haplotypes were associated with lower self-reported anxiety ratings across the stressor. Results extend prior work pointing to the influence of MIF signaling on neuroendocrine response to stress and suggest a potential pathophysiological pathway underlying risk for stress-related physical and mental health disorders. To our knowledge, these are the first data showing associations between the MIF gene, HPA axis reactivity, and anxiety symptoms during adolescence.

AB - Emerging evidence points to interactions between inflammatory markers and stress reactivity in predicting mental health risk, but underlying mechanisms are not well understood. Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine involved in inflammatory signaling and Hypothalamus Pituitary Adrenal (HPA) axis stress-response, and has recently been identified as a candidate biomarker for depression and anxiety risk. We examined polymorphic variations of the MIF gene in association with baseline MIF levels, HPA axis reactivity, and self-reported anxiety responses to a social stressor in 74 adolescents, ages 10–14 years. Genotyping was performed for two polymorphisms, the -794 CATT5-8 tetranucleotide repeat and the -173*G/C single nucleotide polymorphism (SNP). Youth carrying the MIF-173*C and CATT7 alleles displayed attenuated cortisol reactivity when compared with non-carriers. Children with the CATT7-173*C haplotype displayed lower cortisol reactivity to the stressor compared to those without this haplotype. Additionally, the CATT5-173*C and CATT6-173*C haplotypes were associated with lower self-reported anxiety ratings across the stressor. Results extend prior work pointing to the influence of MIF signaling on neuroendocrine response to stress and suggest a potential pathophysiological pathway underlying risk for stress-related physical and mental health disorders. To our knowledge, these are the first data showing associations between the MIF gene, HPA axis reactivity, and anxiety symptoms during adolescence.

KW - Adolescents

KW - Anxiety

KW - Cortisol

KW - Cytokine

KW - HPA-axis

KW - MIF

KW - Stress reactivity

KW - Stress response

UR - http://www.scopus.com/inward/record.url?scp=85047827636&partnerID=8YFLogxK

U2 - 10.1016/j.psyneuen.2018.05.033

DO - 10.1016/j.psyneuen.2018.05.033

M3 - Article

C2 - 29870971

AN - SCOPUS:85047827636

VL - 95

SP - 170

EP - 178

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

SN - 0306-4530

ER -