Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

Benachenhou, Sérine; Etcheverry, Antoine; Galarneau, Luc; Dubé, Jean; Çaku, Artuela

doi:10.1002/aur.2183

Cited by 23 publications

(17 citation statements)

References 48 publications

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“…In addition, lower LRs cholesterol was associated with a higher score of autistic traits as evaluated by the SCQ questionnaire. These data agree with our previous report in ASD population that showed an increase of cognitive impairment risk when the plasma cholesterol is below the 10th centile of normalized population 45 . Taken together, these findings suggest a potential mechanistic implication of low cholesterol in cognitive dysfunction of FXS individuals probably through disruption of cholesterol content in LRs.…”

Section: Discussionsupporting

confidence: 93%

Association of lipid rafts cholesterol with clinical profile in fragile X syndrome

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Benachenhou

Abolghasemi

et al. 2022

Sci Rep

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Fragile X syndrome (FXS) is the most prevalent monogenic cause of intellectual disability and autism spectrum disorder (ASD). Affected individuals have a high prevalence of hypocholesterolemia, however, the underlying mechanisms and the clinical significance remains unknown. We hypothesized that decrease in the plasma cholesterol levels is associated with an alteration of cholesterol content within the lipid rafts (LRs) which ultimately affects the clinical profile of FXS individuals. The platelets LRs were isolated by ultracentrifugation on sucrose gradient from 27 FXS and 25 healthy controls, followed by measurements of proteins, cholesterol, and gangliosides content. Autistic and adaptive behaviour of affected individuals were respectively assessed by the Social Communication Questionnaire and Adaptive Behavior Assessment System. Our results suggest a decrease in the cholesterol content of LRs in FXS individuals as compared to controls. As opposed to controls, LR cholesterol was significantly associated with plasma total cholesterol (r = 0.47; p = 0.042) in the FXS group. Furthermore, the correlation between LRs cholesterol and the clinical profile showed a significant association with autistic traits (r = − 0.67; p < 0.001) and adaptative behavior (r = 0.70; p < 0.001). These results support the clinical significance of LR cholesterol alterations in FXS. Further studies are warranted to investigate the implication of LRs in FXS pathophysiology and ASD.

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Section: Discussionsupporting

confidence: 93%

Association of lipid rafts cholesterol with clinical profile in fragile X syndrome

Toupin

Benachenhou

Abolghasemi

et al. 2022

Sci Rep

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“…The lower levels of cholesterol detected in PRRSVchallenged pigs relative to control gilts indicate that MIA may cause hypocholesterolemia. Serum hypocholesterolemia has been associated with autism spectrum disorder, a neurodevelopmental and behavioral disorder linked to MIA (Benachenhou et al, 2019).…”

Section: Effects Of Maternal Immune Activation On Metabolic Profilesmentioning

confidence: 99%

Impact of Weaning and Maternal Immune Activation on the Metabolism of Pigs

Southey

Bolt

Rymut

et al. 2021

Front. Mol. Biosci.

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Weaning wields environmental, social, and nutritional stresses that are detectable in the blood metabolite levels of the offspring. Prenatal stress in the form of maternal immune activation (MIA) in response to infection, which is associated with health and behavior disorders, also elicits prolonged changes in blood and brain cytokine and metabolite levels of the offspring. The goal of this study was to investigate the effects of weaning and MIA on the offspring’s liver function to advance the understanding of the impact of stressors on peripheral and central nervous systems, physiology, and health. Gas chromatography–mass spectrometry analysis was used to compare the level of hepatic metabolites from 22-day-old pigs (n = 48) evenly distributed among weaning (nursed or weaned), viral MIA exposure (yes or no), and sexes. Weaning effects were detected on 38 metabolites at p-value < 0.05 (28 metabolites at FDR p-value < 0.05), and sex-dependent MIA effects were detected on 11 metabolites. Multiple intermediate and final products of the enriched (FDR p-value < 0.05) glycolysis and gluconeogenesis and pentose phosphate pathways were over-abundant in nursed relative to weaned pigs. The enriched pathways confirm the impact of weaning on hepatic metabolic shift, oxidative stress, and inflammation. Higher levels of the glucogenic amino acid histidine are observed in pigs exposed to MIA relative to controls, suggesting that the role of this metabolite in modulating inflammation may supersede the role of this amino acid as an energy source. The lower levels of cholesterol detected in MIA pigs are consistent with hypocholesterolemia profiles detected in individuals with MIA-related behavior disorders. Our findings underline the impact of weaning and MIA stressors on hepatic metabolites that can influence peripheral and central nervous system metabolic products associated with health and behavior disorders.

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“…Moreover, a retrospective case-control study of a group of French-Canadian ASD individuals observed four times more hypocholesterolemia in ASD than in the general population [28]. Furthermore, low TC in ASD was associated with higher rates of ASD-associated intellectual disability and anxiety/depression [28]. These results suggest that decreased level of TC may be related to ASD.…”

Section: Discussionmentioning

confidence: 97%

“…Interestingly, a nested case-control study demonstrated that lower maternal postpartum plasma LDL concentration was associated with increased odds of ASD in offspring [27]. Moreover, a retrospective case-control study of a group of French-Canadian ASD individuals observed four times more hypocholesterolemia in ASD than in the general population [28]. Furthermore, low TC in ASD was associated with higher rates of ASD-associated intellectual disability and anxiety/depression [28].…”

Section: Discussionmentioning

confidence: 99%

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

Chen

et al. 2021

Lipids Health Dis

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Background About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon. Methods A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents. Results Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors. Conclusions Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

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Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

Cited by 23 publications

References 48 publications

Association of lipid rafts cholesterol with clinical profile in fragile X syndrome

Association of lipid rafts cholesterol with clinical profile in fragile X syndrome

Impact of Weaning and Maternal Immune Activation on the Metabolism of Pigs

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

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