Association between telomere length and cortical thickness in adults with adhd

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by symptoms of inattention, hyperactivity, and impulsivity. These symptoms often first present during childhood or adolescence and can persist into adulthood. Adult ADHD has been associated with a range of features, including psychiatric comorbidities, brain traits, and molecular phenotypes. One such molecular feature is the shortening of telomere length (TL). Telomeres are structures located at the end of chromosomes that protect them from damage during cell division. Shorter TL is a potential marker of cellular aging and has been linked to a variety of health outcomes, including the risk for psychiatric disorders and alterations in brain structure and function. Findings concerning ADHD and TL have been mixed, some studies have suggested that individuals with ADHD may have shorter telomeres compared to those without the disorder. This study utilized two time points selected from our longitudinal study. The first time point (T1) involved the collection of DNA and standardized psychiatric interviews, while the second time point (T2), which occurred an average of 14 years after T1, also included MRI scans. At T1, we assessed telomere length (TL) in 238 individuals with ADHD (mean age=32.33; 53% female) and 125 healthy controls (mean age=31.25; 50% female). At T2, TL was assessed in a subsample of 107 subjects (39 ADHD cases and 68 healthy controls) with accompanying MRI data. DNA was extracted from peripheral blood, and TL was measured in triplicate using quantitative multiplex PCR. Our analysis focused on evaluating the association between normalized TL and ADHD, as well as other outcomes of interest, such as lifetime psychiatric comorbidities and measures of cortical thickness. Our initial findings presented here are focused on T1 data. We observed that subjects with ADHD had shorter telomeres compared to the healthy controls (p=0.024). Furthermore, females had shorter telomeres than males (p=0.019). Additionally, we also identified a negative correlation between telomere length and age (p=0.021). To investigate the association between telomere length and other outcomes, such as neuroimage features and psychiatric comorbidities, we applied a multiple linear regression model. This model included sex, age, and ADHD diagnosis as covariates. Our results indicated that telomere length was predictive of superior frontal gyrus cortical thickness (beta= -0.227, R²= 0.029, p=0.018) and lifetime diagnosis of substance use disorder (beta= 0.104, R²= 0.051, p=0.05). These are preliminar and very promissive results, nevertheless additional analyses will be performed to scrutinize these findings and their relations, besides include and compare our longitudinal data. Overall, our preliminary findings provide additional evidence for TL as a potential biomarker for ADHD, its brain features and psychiatric comorbidities. In addition to the future analyses of our own data, further research is needed to clarify the implications of TL in the neurobiology of ADHD.