Developmental Pattern Of Diurnal Cortisol Rhythm And Associations With Psychopathological Symptoms During Pubertal Transition

Objectives To examine the developmental trajectories of diurnal cortisol rhythm during pubertal transition,and investigate sex-specific associations with psychopathological symptoms.MethodsBased on the child health cohort in Ma’anshan of Anhui Province established in October 2015(T0),a total of 1158 children(mean age = 8.04 years)in grade 2 to 3from three elementary schools were recruited in this study with informed consent.And follow-up surveys were conducted in October 2016(T1),October 2017(T2)and October 2018(T3),respectively.Demographic information was collected through questionnaire,including birth date,parental education,household monthly income,warm parenting,adverse childhood experiences and falling asleep and getting up time.Psychopathological symptoms including internalizing and externalizing symptoms were assessed by the Mac Arthur Health & Behavior Questionnaire for Late Childhood and Adolescence(9-18 years)(HBQ-C)at follow-ups.Height and weight were assessed during each follow-up to calculate BMI.Breast Tanner stages in girls and testicular volume in boys were assessed annually.In T0,awakening saliva was collected in the morning immediately after waking up.At T1 to T3,saliva samples were collected at three time points at one weekday: upon waking in the morning,30 min after waking and before bedtime.Salivary cortisol concentration was assessed by using double-antibody sandwich enzyme-linked immunosorbent assay,and four indices of diurnal cortisol rhythm were calculated:morning awakening cortisol,the area under the curve(AUC),cortisol awakening response(CAR)and the diurnal cortisol slope(DCS).The CAR,AUC and DCS were all conducted natural log conversion to correct for a strong positive skew in the distribution(ln AUC、ln DCS 和 ln CAR).Using multilevel mixed-effect linear models in Stata to identify the trajectories of morning awakening cortisol with puberty in boys and girls based on data collected from T0 to T3,and ln AUC,ln CAR and ln DCS used data from T1 to T3.Similar strategy was applied in analyzing the correlation between psychopathological symptoms with diurnal cortisol rhythm.ResultsAt baseline(T0),90.73% of girls and 99.18% of boys were at pre-puberty.Pubertal stage was varied by sex(χ2=141.349,P<0.001)such that most of girls(93.67%)reached puberty onset while only 59.53% of boys entered puberty at T3.Average scores of internalizing and externalizing symptoms assessed at T2 were2.84±0.52 and 1.99±0.58,there were no significant associations in internalizing symptoms(2.87 vs.2.83;t = 0.12,P = 0.793)or externalizing symptoms(2.03 vs.1.95;t = 2.56,P = 0.856)between boys and girls.The percentages of participants with scores above cutoffs on internalizing and externalizing symptoms were 13.13% and7.51% at T1 and increased to 14.26%(χ2 = 32.978,P<0.001)and 14.54%(χ2 =17.219,P<0.001)at T3,respectively.After controlling for age,BMI,psychopathological symptoms,parental education,warm parenting,household monthly income,sleep duration and adverse childhood experiences,the results of multilevel mixed-effect linear models indicated that awakening cortisol(β =-0.005,P = 0.004)and total amount of diurnal cortisol secretion(ln AUC,β =-0.005,P = 0.040)decreased with pubertal development in boys while no significant pubertal changes in diurnal cortisol measures in girls were found(awakening cortisol:β =-0.004,P = 0.236;ln CAR: β = 0.010,P = 0.671;ln AUC: β =-0.006,P = 0.278;ln DCS: β =-0.097,P = 0.345).There were no significant association between ln CAR(β = 0.001,P = 0.935)and ln DCS(β =-0.082,P = 0.100)with testicular volume.After adjusting for age,BMI,pubertal development,parental education,warm parenting,household monthly income,sleep duration and adverse childhood experiences,the finding of multilevel mixed-effect linear model showed higher awakening cortisol and higher ln AUC predicted higher internalizing symptom scores in girls(awakening cortisol: β = 0.82,95%CI:0.36～1.28,P < 0.001;ln AUC: β = 0.62,95%CI:0.14～1.11,P = 0.012)and higher scores on externalizing symptom in boys(awakening cortisol: β = 0.73,95%CI:0.29～1.16,P = 0.001;ln AUC: β = 0.55,95%CI:0.09～1.01,P = 0.019).ConclusionThis study explored the trajectories of four indices of diurnal cortisol rhythm with pubertal development and the sex-specific associations between circadian cortisol rhythm with mental health outcomes based on 3-year follow-ups.The finding suggested that awakening cortisol and total amount of diurnal cortisol secretion significantly decreased with testicular volume while there were no significant pubertal changes in diurnal cortisol measures in girls.Awakening and total amount of diurnal cortisol secretion may serve as markers to predict externalizing symptoms in boys and internalizing symptoms in girls during pubertal transition.