Bioenergetic variation is related to autism symptomatology - PubMed (original) (raw)

. 2017 Dec;32(6):2021-2031.

doi: 10.1007/s11011-017-0087-0. Epub 2017 Aug 29.

Ekim Nur Kilinc 1 2, Li Yin 3, John Slattery 1 2, Marie Tippett 1 2, Rebecca Wynne 1 2, Shannon Rose 1 2, Stephen Kahler 1 2, Shirish Damle 4, Agustin Legido 4, Michael J Goldenthal 4, Richard E Frye 5 6

Affiliations

Leanna Delhey et al. Metab Brain Dis. 2017 Dec.

Abstract

Autism spectrum disorder (ASD) has been associated with mitochondrial dysfunction but few studies have examined the relationship between mitochondrial function and ASD symptoms. We measured Complex I and IV and citrate synthase activities in 76 children with ASD who were not receiving vitamin supplementation or medication. We also measured language using the Preschool Language Scales or Clinical Evaluation of Language Fundamentals, adaptive behavior using the Vineland Adaptive Behavioral Scale, social function using the Social Responsiveness Scale and behavior using Aberrant Behavior Checklist, Childhood Behavior Checklist and the Ohio Autism Clinical Impression Scale. Children with ASD demonstrated significantly greater variation in mitochondrial activity compared to controls with more than expected ASD children having enzyme activity outside of the normal range for Citrate Synthase (24%), Complex I (39%) and Complex IV (11%). Poorer adaptive skills were associated with Complex IV activity lower or higher than average and lower Complex I activity. Poorer social function and behavior was associated with relatively higher Citrate Synthase activity. Similar to previous studies we find both mitochondrial underactivity and overactivity in ASD. This study confirms an expanded variation in mitochondrial activity in ASD and demonstrates, for the first time, that such variations are related to ASD symptoms.

Keywords: Autism Spectrum disorder; Complex I; Complex IV; Electron transport chain; Mitochondrial dysfunction.

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Conflict of interest statement

All authors’ have no conflicts of interest to declare.

Figures

Fig. 1

Fig. 1

Activity of Citrate Synthase and activities of Complex I and IV normalized to Citrate Synthase for children with Autism Spectrum Disorder (ASD). For each graph the control mean and minimal and maximum limits of normal controls are provided on the right. Individual participant data is provided in the center of each graph with individuals having values outside of the normal range highlighted in red. The mean of the ASD group is depicted on the left of the individual data points as diamond

Fig. 2

Fig. 2

Mitochondrial enzymes activities (uncorrected) demonstrate moderate correlations. Shaded area represents the normal range with the horizontal and vertical black lines representing the mean of the control group

Fig. 3

Fig. 3

Vineland Adaptive Behavior Scale subscales are related to uncorrected Complex IV activity. Shaded area represents the normal range with the vertical black line representing the mean of the control group. Blue points represent children with ASD while the orange points represent typically developing control children

Fig. 4

Fig. 4

Vineland Adaptive Behavior Scale subscales are related to uncorrected Complex I activity in a linear manner. Shaded area represents the normal range with the vertical black line representing the mean of the control group. Blue points represent children with ASD while the orange points represent typically developing control children

Fig. 5

Fig. 5

Social Responsiveness Scale subscales are related to Citrate Synthase activity. Shaded area represents the normal range with the vertical black line representing the mean of the control group

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