Association between blood mitochondrial DNA copy number and mental disorders: A bidirectional two-sample mendelian randomization study.

BACKGROUND: Mitochondria is essential for cellular energy production, oxidative stress, and apoptosis. Mitochondrial DNA (mtDNA) encodes essential proteins for mitochondrial function. Although several studies have explored the association between changes in mtDNA copy number (mtDNA-CN) and risk of mental disorders, the results remain debated. This study used a bidirectional two-sample Mendelian randomization (MR) analysis to examine the genetic causality between mtDNA-CN and mental disorders. METHODS: Genome-wide association study (GWAS) data for mtDNA-CN were sourced from UK biobank, involving 383,476 European cases. GWAS data for seven mental disorders-attention deficit/hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, anxiety, and obsessive-compulsive disorder-were primarily obtained from the Psychiatric Genomics Consortium. Causal associations were assessed using inverse variance weighting, with sensitivity analyses via the weighted median and MR-Egger methods. Reverse MR considered the seven mental disorders as exposures. All analyses were replicated with additional mtDNA-CN GWAS data from 465,809 individuals in the Heart and Ageing Research in Genomic Epidemiology consortium and the UK Biobank. RESULTS: Forward MR observed a 27 % decrease in the risk of ASD per standard deviation increase in genetically determined blood mtDNA-CN (OR = 0.73, 95%CI: 0.58-0.92, p = 0.002), with no causal effects on other disorders. Additionally, reverse MR did not indicate a causal association between any of the mental disorders and mtDNA-CN. Validation analyses corroborated these findings, indicating their robustness. CONCLUSIONS: Our study supports the potential causal association between mtDNA-CN and the risk of ASD, suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.

Comparison of the Clancy Autism Behavior Scale and Autism Behavior Checklist for Screening Autism Spectrum Disorder.

PURPOSE: To make early detection of individuals with autism spectrum disorder (ASD), caregiver-report instruments remain an efficient and adaptable option for the preliminary assessment. This study aimed to compare the psychometric properties of the Clancy Autism Behavior Scale (CABS) and Autism Behavior Checklist (ABC) as screening tools for ASD by caregivers. METHODS: The data were collected from 154 pairs of children and their parents, who sought medical attention for suspected autism at Peking University Sixth Hospital. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Youden index, and area under the receiver operating characteristics curves (AUC) of the CABS and ABC were calculated and compared using recommended cut-off values from initial papers. The optimal cut-off values for CABS and ABC were determined according to the maximum Youden index. RESULTS: The ABC performed better than the CABS in screening autistic persons. Specifically, the ABC demonstrated higher sensitivity than the CABS in identifying children with ASD, while the CABS exhibited superior specificity compared to the ABC. According to the maximum Youden index, the optimal cut-off value was determined to be 13 for CABS and 62 for ABC. CONCLUSION: The ABC exhibits higher sensitivity and overall performance in screening individuals with ASD compared to the CABS. The ABC is more suitable as a screening tool for caregivers in both domestic and clinical settings, while the CABS may be utilized when evaluation time or medical resources are limited due to its shorter completion time and fewer items.