Exploring the genetic and socioeconomic interplay between ADHD and anxiety disorders using Mendelian randomization.

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.

Abnormal Serum BDNF and p-mTOR in MDD in Adolescents with Childhood Trauma.

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.

Different serum protein factor levels in first-episode drug-naive patients with schizophrenia characterized by positive and negative symptoms.

AIM: The clinical features of schizophrenia can be mainly divided into two symptom domains: positive and negative. Patients in each symptom domain respond differently to treatments, and their prognoses vary accordingly. Serum protein factors, such as nerve growth factor (NGF), neurotrophin-3 (NT-3), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and the calcium-binding protein, S100ß, have been reported to be involved in the pathogenesis of schizophrenia. However, their roles in the positive and negative symptom domains have not been determined. In this study, we investigated whether the serum levels of these five protein factors differed among first-episode drug-naive schizophrenia patients in each symptom domain and in healthy controls. METHODS: Double-antibody sandwich ELISA were used to quantify the amounts of the five protein factors in serum. RESULTS: Compared with the levels in the controls (n = 60), increased serum levels of IL-6, IL-1ß, and S100ß and decreased serum levels of NGF and NT-3 were observed in first-episode drug-naive schizophrenia patients. Additionally, the serum levels of IL-6 and IL-1ß were significantly higher in schizophrenia patients characterized by negative symptoms (negative group, n = 37) than in those characterized by positive symptoms (positive group, n = 46). Based on multivariate regression analyses, serum levels of IL-1ß were positively associated with the Negative Symptom subscore of the Positive and Negative Syndrome Scale in the negative group and in all patients with schizophrenia. CONCLUSION: The two subtypes of schizophrenia may have different pathological mechanisms. Patients characterized by negative symptoms probably have more serious disturbances in neuroimmunology.