Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous
neurological disease in childhood, a growing body of evidence associates it with mitochondrial
dysfunction explaining the observed comorbidities.
Introduction: The aim of this study is to identify variations in cellular bioenergetics and
metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral
Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular
pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease.
Methods: PBMC from children with ASD and a control group of the same age and gender were isolated.
All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian
children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed
with a Seahorse XFp analyzer.
Results: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity
(by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative
stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and
impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the
control group. These results can contribute to a better understanding of the underlying causes of
ASD, which is crucial for selecting a successful treatment.
Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics
and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities
that do not allow mitochondria to adapt and meet the increased energetic requirements
of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead
to the discovery of new approaches for nutrition and therapy.