A Three-Way Interaction of Sex, PER2 rs56013859 Polymorphism, and Family Maltreatment in Depressive Symptoms in Adolescents.

The prevalence of depressive symptoms in adolescents is 12-18% and is twice as frequent in females. Sleep problems and thoughts of death are depressive symptoms or co-occurrent phenomena. Family maltreatment is a risk factor for later depressive symptoms and the period circadian regulator (PER) has been studied in relation to neurotransmitters, adaptation to stress, and winter depression. The purpose of this work was to study the relation of the three-way interactions of sex, PER2 rs56013859, and family maltreatment in relation to core depressive symptoms, sleep complaints, and thoughts of death and suicide in self-reports from a cohort of Swedish adolescents in 2012, 2015, and 2018. Cross-sectional and longitudinal analyses with linear and logistic regressions were used to study the relationships to the three outcomes. The three-way interaction was related to core depressive symptoms at both baseline and six years later. In contrast, the model did not show any relation to the other dependent variables. At 13-15 years, a sex-related differential expression was observed: females with the minor allele C:C/C:T exposed to family maltreatment showed higher levels of core depressive symptoms. Six years later, the trend was inverted among carriers of minor alleles.

Exploration of the Moderating Effects of Physical Activity and Early Life Stress on the Relation between Brain-Derived Neurotrophic Factor (BDNF) rs6265 Variants and Depressive Symptoms among Adolescents.

Depression affects one in five persons at 18 years of age. Allele A of the brain-derived neurotrophic factor (BDNF) rs6265 is considered to be a risk factor for depression. Previous studies of the interaction between BDNF rs6265, early adversity, and/or physical activity have shown mixed results. In this study, we explored the relation between BDNF rs6265 polymorphism and childhood stress, as well as the moderating effect of physical activity in relation to depressive symptoms using binary logistic regressions and process models 1, 2 and 3 applied to data obtained at three times (waves 1, 2 and 3) from the Survey of Adolescent Life in Västmanland cohort study (SALVe). Results revealed that both childhood stress and physical activity had a moderation effect; physical activity in wave 1 with an R2 change = 0.006, p = 0.013, and the Johnson−Neyman regions of significance (RoS) below 1.259, p = 0.05 for 11.97%; childhood stress in wave 2 with the R2 change = 0.008, p = 0 002, and RoS below 1.561 with 26.71% and >4.515 with 18.20%; and a three-way interaction in wave 1 in genotype AA carriers. These results suggest that allele A is susceptible to physical activity (positive environment) and childhood stress (negative environment).

Breastfeeding moderates the relationship between fat mass and obesity-associated gene rs9939609 and body mass index among adolescents.

OBJECTIVE: Breastfeeding, which is important for early growth, is a possible moderator of genetic influence, such as the effect of the fat mass and obesity-associated gene (FTO) on body mass index (BMI). The aim of this study was to assess the moderating effect of breastfeeding duration on the relationship between FTO rs9939609 and BMI in a Caucasian sample. METHODS: Adolescents born in 1997 and in 1999, who were living in the Swedish county Västmanland in 2012, were invited to participate in the Survey of Adolescent Life in Västmanland. The adolescents and their parents completed self-reported questionnaires in 2012, 2015, and 2018. Genotyping of rs9939609 T > A polymorphism was conducted from saliva DNA samples. Interaction effects of parental reported breastfeeding duration in months, including regions of significance, on the relationship between rs9939609 and BMI plus overweight were assessed. RESULTS: Considering physical activity levels, parental reported breastfeeding duration was a moderator of the relationship between rs9939609 and BMI for the younger (regions of significance = <1.6 and >28.1 months) and older adolescents (region of significance = >19.9 months), but not for the young adults. Plots of the association between breastfeeding duration and BMI showed higher BMI for AA with short breastfeeding, but lower BMI with longer breastfeeding than AT and TT. Longer breastfeeding lowered the odds for overweight among the younger adolescents, especially among AA individuals. CONCLUSION: Rs9939609 AA individuals were more susceptible than AT and TT individuals to both short and long breastfeeding durations, which is consistent with the differential susceptibility hypothesis. FTO rs9939609 AA might be a plasticity variant with differential susceptibility to environmental influences. Breastfeeding duration may be one of many factors that affect the relationship between rs9939609 and BMI.

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants.

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.