Investigation of the relationship between cognitive functions and the endocannabinoid system, BDNF, klotho and NfL in patients diagnosed with attention-deficit/hyperactivity disorder

AIM: In our study, we aimed to investigate the relationship between cognitive functions and the levels of AEA, 2-AG, BDNF, NfL, and klotho in adults diagnosed with ADHD and healthy individuals. MATERIALS AND METHODS: The study included 52 adult patients diagnosed with ADHD who were followed up at the outpatient clinics of Sakarya Training and Research Hospital, along with 50 healthy control participants. All individuals completed a sociodemographic data form and underwent neuropsychiatric testing. Serum levels of AEA, 2-AG, BDNF, klotho, and NfL were measured in both the patient and control groups. RESULTS: No significant differences were found in biomarker levels between patients and healthy controls. ADHD patients performed worse on neuropsychiatric tests. In the CT, the ADHD group was found to perform worse than the control group, with the difference being particularly pronounced on the left side. Serum biomarker levels correlated with cognitive functions, and these associations differed between groups. In the patient group, regression analysis revealed that AEA levels predicted inattention severity and total ADHD scores. AEA levels were negatively correlated with inattention severity and the severity and frequency of ADHD-related problems. 2-AG levels were negatively correlated with hyperactivity/impulsivity severity. Serum biomarker levels showed moderate-to-strong intercorrelations in both groups. Differences in AEA, 2-AG, and NfL were observed between medicated and unmedicated ADHD patients. CONCLUSION: The relationship between serum levels of AEA, 2-AG, BDNF, klotho, and NfL and cognitive functions appears to differ between the two groups, and these differences seem to be linked to a regulatory mechanism rather than to variations in the mean serum concentrations of these molecules. Despite being matched for age and education level, patients with ADHD demonstrated notable impairments in cognitive performance. The findings also suggest that serum endocannabinoid levels may be associated with the severity of ADHD symptoms. Keywords: ADHD, BDNF, endocannabinoid, klotho, NfL