ABSTRACT
Background: ADHD and anxiety disorders often co-occur, sharing symptoms and dysfunctions, yet the underlying mechanisms remain elusive. Methods: To explore the shared and distinct genetic variations between ADHD and anxiety disorders, we applied Mendelian randomization (MR) analysis to ADHD, anxiety disorders, and three socioeconomic factors: income, educational attainment (EA), and intelligence. MR analysis utilized genome-wide association study summary datasets (anxiety disorder: 7,016 cases and 14,745 controls; ADHD: 38,691 cases and 275,986 controls; EA: 766,345 participants; intelligence: 146,808 participants; household income: 392,422 participants), with inverse-variance weighting as the primary method. Results: Our MR analysis revealed no discernible genetic-level causal effect between ADHD and anxiety disorders (p > 0.77). Additionally, the independent variables for ADHD (25 SNPs) and anxiety disorders (18 SNPs) did not overlap, highlighting the genetic distinction between the two conditions. Higher income (p < 0.002) and EA (p < 0.005) were found to serve as protective factors for both ADHD and anxiety disorders. Genetic predisposition to higher income (86 SNPs) and EA (457 SNPs) were identified as a potential common protective factors for both conditions. Lastly, genetic predisposition to higher intelligence was found to potentially guard against ADHD (p < 0.001) but not against anxiety disorders (p > 0.55). Conclusion: Our findings indicate that the shared symptoms observed between ADHD and anxiety disorders are more likely influenced by genetic predispositions related to socioeconomic factors rather than by the genetic predispositions specific to the disorders themselves.
ABSTRACT
Background: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma. Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control. Results: The serum levels of BDNF were significantly lower (p<0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p<0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=-0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value. Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.