Anxiety and Depression Traits Are Moderated by a Sex-Dependent Genetic Interaction Between 5-HTTLPR and BDNF

Serotonin transporter polymorphism (5-HTTLPR) is associated with post-awakening cortisol measures in previous depression

Elevated cortisol levels have been linked to major depressive disorder (MDD), but cortisol dynamics vary substantially across individuals and clinical states. Genetic variation in the serotonin transporter polymorphism (5-HTTLPR) has been proposed as one contributor to differences in hypothalamic-pituitary-adrenal axis functioning. The present study examined associations between cortisol awakening measures and 5-HTTLPR genotype groups in individuals with a history of depression compared with healthy controls, and explored whether current depressive symptom severity was related to cortisol indices. A total of 108 individuals with a history of depression were genotyped and compared with 59 healthy controls. Participants completed structured diagnostic interviews and self-reported depressive symptoms. Salivary cortisol was sampled in the evening and at five consecutive timepoints after awakening (15-min intervals). Cortisol was analyzed using a linear mixed-effects model of repeated measures and by cortisol awakening response (CAR) summary indices: area under the curve with respect to ground (AUCg) and area under the curve with respect to increase (AUCi). Cortisol changed significantly over time, but there was no evidence that genotype groups differed in the overall cortisol timecourse. In CAR summary analyses, group differences were observed for AUCg, whereas AUCi did not show corresponding group differences. Regression analyses indicated that BDI-II was not associated with AUCg or AUCi after adjustment for covariates. These findings suggest that 5-HTTLPR-related differences, when present, may be more detectable in overall post-awakening cortisol output than in baseline-relative increase.

Exploring the influence of BDNF Val66Met gene polymorphism and coping mechanisms on depression, anxiety, and stress among allied health sciences undergraduates

Mental health is influenced by genetic and psychological factors. While higher education supports personal and professional growth, it also poses challenges to student well-being. This research aimed to explore the influence of BDNF Val66Met gene polymorphisms and coping mechanisms on mental health among medical and allied health sciences undergraduates at Universiti Malaysia Sabah. A total of 109 undergraduates completed a series of questionnaires, including a demographic questionnaire, the Depression, Anxiety, Stress Scale-21 (DASS-21), the Brief-Coping Orientation to Problems Experienced (Brief-COPE), and the World Health Organisation Quality of Life – BREF (WHOQOL-BREF). Participants then submitted their saliva samples for gene polymorphism analysis. Results showed that 20.2% of participants had severe to extremely severe symptoms of depression, 43.1% for anxiety, and 15.6% for stress. While homozygous Met allele carriers (Met/Met) had higher mean anxiety and stress scores than Val allele carriers (Val/Val and Val/Met), the differences were not statistically significant. For homozygous Met allele carriers, problem-focused coping showed a negative correlation, whereas emotion-focused coping showed a positive correlation with depression and stress. Avoidant-focused coping was positively predicted by depression among Val allele carriers. Importantly, the Multivariate Analysis of Covariance (MANCOVA) indicated that coping strategies exerted a stronger influence on mental health outcomes than BDNF genotype, even after controlling for demographic variables. Additionally, the psychological quality-of-life subscale significantly predicted mental health outcomes. These findings highlight the need for coping-based interventions to improve students' mental well-being, as well as further research into genetic influences.

Relationship between BDNF rs6265 (VAL66MET) polymorphism and serum BDNF LEVELS in anxiety disorders

association of BDNF Val66Met polymorphism with hPa and saM axis reactivity to psychological and physical stress

Exploratory study of the association between blood immune markers and clinical symptoms in adolescent depression: Stratified by body mass index.

BACKGROUND Major Depressive Disorder (MDD) and obesity are prevalent and burdensome public health issues linked by a complex, bidirectional association potentially driven by systemic inflammation. Nevertheless, this relationship remains poorly understood in adolescents with MDD. METHODS We enrolled 339 adolescents with MDD and stratified them by body mass index (BMI) into underweight, normal weight, overweight, and obese groups. Depression and anxiety severity were evaluated using the Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Rating Scales. Hematological inflammatory markers, including neutrophils, monocytes, lymphocyte, platelets, white blood cells, high-sensitivity C-Reactive Protein (hs-CRP), derived ratios, and systemic immune-inflammation index (SII), were assessed across groups. Linear regression and mediation analyses evaluated associations among clinical symptoms, BMI, and inflammatory markers. RESULTS The association between BMI and depressive symptoms differed significantly by sex. Among females, the abnormal BMI group had significantly higher total HAMD scores than the normal-weight group, with the obese group demonstrating a higher score on the cognitive impairment factor of HAMD. Inflammatory markers increased progressively across ascending BMI categories. BMI and blood inflammatory markers were associated with depression severity in adolescents. Neutrophil count and monocyte-to-lymphocyte ratio (MLR) showed significant positive indirect effects, accounting for part of the association between obesity and depressive symptoms. CONCLUSIONS High BMI correlates with more severe depressive symptoms and increased inflammatory status in adolescents with MDD, especially among females. Systemic inflammation partially accounts for the association between high BMI and depression, suggesting that interventions targeting immune and metabolic pathways may offer additional therapeutic benefits.

The Longitudinal Association Between Parent-Child Attachment and Adolescent Depressive Symptoms: Moderation by Oxytocin Receptor Polymorphisms

Maternal and paternal attachment may relate differently to adolescent depressive symptoms, but the potential contribution of oxytocin receptor (OXTR) gene single nucleotide polymorphisms (SNPs) to these associations remains unclear. This six-month longitudinal study included 746 seventh- and tenth-grade students (50.7% female) from Guangzhou, China. Parent-child attachment and saliva samples for genotyping were collected at baseline, and depressive symptoms were assessed at follow-up using the CES-D-10. Overall, 48.8% of adolescents screened positive for depressive symptoms. Compared with adolescents below the cutoff, those who screened positive reported lower parental trust/communication and higher alienation (all p < 0.01). In adjusted linear regression models, father-child trust/communication was negatively associated with subsequent depressive symptoms (β = −0.26, p < 0.01), whereas mother-child alienation was positively associated with subsequent depressive symptoms (β = 0.15, p = 0.02). Exploratory moderation analyses showed a nominal rs2254295 × mother-child alienation interaction before correction (β = −0.07, p = 0.046), but this effect did not survive FDR correction. Father-child trust/communication and mother-child alienation showed distinct associations with adolescent depressive symptoms. The possible moderating role of OXTR rs2254295 should be regarded as preliminary and requires replication in larger independent samples.