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. 2023 Nov 17;14(1):44.
doi: 10.1186/s13229-023-00577-y.

Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study

Simon Maier  1 , Kathrin Nickel  2 , Thomas Lange  3 , Georg Oeltzschner  4   5 , Michael Dacko  3 , Dominique Endres  2 , Kimon Runge  2 , Anke Schumann  6 , Katharina Domschke  2 , Michalis Rousos  2 , Ludger Tebartz van Elst  2
Affiliations

Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study

Simon Maier et al. Mol Autism. .

Abstract

Introduction: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs).

Materials and methods: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated.

Results: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p = 0.028; Cohen's d = 0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p = 0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels.

Limitations: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality.

Conclusion: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function.

Keywords: Autism spectrum disorder; Lactate; Magnetic resonance spectroscopy; Mitochondria; Mitochondrial dysfunction; Posterior cingulate cortex.

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Conflict of interest statement

KD: Steering Committee Neurosciences, Janssen. LTvE: Advisory boards, lectures, or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag, Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors declare that they do not have any conflicts of interest.

Figures

Fig. 1
Fig. 1
MRS voxel Placement in the Posterior Cingulate Cortex and Aggregate OFF and Difference Spectra. The figure displays the superimposed MRS voxel placements for all participants within the posterior cingulate cortex, as shown in the sagittal (A) and transversal (B) views. The average spectra are represented by the green line, with the gray shading indicating standard deviation, and the yellow line depicting the model fit for the editing-off (C) and difference editing spectra (D)
Fig. 2
Fig. 2
Comparison of Lac+ Concentration in the Posterior Cingulate Cortex between ASD and NTC Groups via Boxplot. This figure illustrates the significant difference (p = 0.028) in the mean Lac+ concentration between the ASD and NTC groups in the posterior cingulate cortex. Notches indicate the standard deviation
Fig. 3
Fig. 3
Correlation Matrix of Psychometric Scores and Age with Lac+ Concentration and fractional Voxel Volumes. This matrix shows the correlations among psychometric scores and age with Lac+ concentration and GM/WM/CSF voxel volume fractions in the posterior cingulate cortex for the ASD group (upper graph) and both groups combined (lower graph). Circle size and color indicate the strength of the correlation (“R”). Notations: SRS-2 = Social Responsiveness Scale, AQ = Autism Spectrum Quotient, EQ = Empathy Quotient, BDI-II = Beck Depression Inventory, WURS-k = Wender Utah Rating Scale, STAI = State Anxiety Inventory, GM = Gray Matter, WM = White Matter, CSF = Cerebrospinal Fluid. Significance levels: *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 4
Fig. 4
Scatterplot of Serum and Cerebral Lactate Levels in Posterior Cingulate Cortex. The scatterplot shows serum lactate concentration (x axis) against cerebral Lac+ concentration in the posterior cingulate cortex for the ASD group (red) and NTC group (blue). Regression lines with confidence intervals demonstrate no significant relationship between serum and cerebral lactate levels
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