Michael Maes*, George Anderson, Susana R. Betancort Medina , Moonsang Seo and Johanna O. Ojala Pages 4405 - 4420 ( 16 )
Background: A diverse array of data has been associated with autism spectrum disorder (ASD), reflecting the complexity of its pathophysiology as well as its heterogeneity. Two important hubs have emerged, the placenta/prenatal period and the postnatal gut, with alterations in mitochondria functioning crucial in both.
Methods: Factors acting to regulate mitochondria functioning in ASD across development are reviewed in this article. Results: Decreased vitamin A, and its retinoic acid metabolites, lead to a decrease in CD38 and associated changes that underpin a wide array of data on the biological underpinnings of ASD, including decreased oxytocin, with relevance both prenatally and in the gut. Decreased sirtuins, poly-ADP ribose polymerase-driven decreases in nicotinamide adenine dinucleotide (NAD+), hyperserotonemia, decreased monoamine oxidase, alterations in 14-3-3 proteins, microRNA alterations, dysregulated aryl hydrocarbon receptor activity, suboptimal mitochondria functioning, and decreases in the melatonergic pathways are intimately linked to this. Many of the above processes may be modulating, or mediated by, alterations in mitochondria functioning. Other bodies of data associated with ASD may also be incorporated within these basic processes, including how ASD risk factors such as maternal obesity and preeclampsia, as well as more general prenatal stressors, modulate the likelihood of offspring ASD. Conclusion: Such a mitochondria-focussed integrated model of the pathophysiology of ASD has important preventative and treatment implications.Autism, mitochondria, melatonin, microRNAs, gut microbiome, aryl hydrocarbon receptor.
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, CRC Scotland & London, Eccleston Square, London, CRC Scotland & London, Eccleston Square, London, Great Ormond Street Hospital for Children NHS Foundation Trust, London, Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio