The role of insulin/IGF1 signalling in neurodevelopmental and neuropsychiatric disorders – Evidence from human neuronal cell models

Réthelyi, János M.; Vincze, Katalin; Schall, Daniel; Glennon, Jeffrey C.; Berkel, Simone

doi:10.1016/j.neubiorev.2023.105330

Cited by 7 publications

(4 citation statements)

References 190 publications

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“…Emotional changes associated with metabolic syndrome are primarily caused by insulin resistance ( 36 , 37 ). The insulin receptor (IR) and insulin-like growth factor 1 (IGF1R) plays an important role in the development of the central nervous system ( 38 ). The common signaling cascade reactions of IR/IGF1R include PI3K/AKT/mTOR and RAS/ERK, and the activation of these pathways plays a role in neurodevelopmental disorders such as intellectual disability (ID) and ASD ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

“…The insulin receptor (IR) and insulin-like growth factor 1 (IGF1R) plays an important role in the development of the central nervous system ( 38 ). The common signaling cascade reactions of IR/IGF1R include PI3K/AKT/mTOR and RAS/ERK, and the activation of these pathways plays a role in neurodevelopmental disorders such as intellectual disability (ID) and ASD ( 38 , 39 ). Additionally, adolescents with ASD and ADHD often have metabolic syndromes and diabetes ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

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Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study

Li,

Zhou

2024

Front. Endocrinol.

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PurposeThe development of multiple system diseases is increased by obesity. However, the connection between obesity and developmental disabilities (DDs) in children is unclear. As an obesity index, the weight-adjusted waist index (WWI) assessed fat distribution and muscle mass. In this study, we examined the correlation between WWI and DDs among children 6 to 17 years of age.MethodsThis study used data from the National Health and Nutrition Examination Survey database (NHANES) covering 2003 to 2018, which included the data of 17,899 participants between 6 and 17 years of age. Data regarding their waist circumference, weight, and DDs were collected via physical examinations and questionnaire, respectively. A person’s WWI is calculated by dividing their waist circumference by their weight squared. The correlation between WWI and DDs was studied using weighted multiple logistic regression models. Additionally, a sensitivity analysis was conducted utilizing a generalized additive model and smooth curve fitting.ResultsAfter adjusting for all covariates, WWI was positively related to DDs in children ages 6-17. Based on the sensitivity analysis, the correlation between the WWI and prevalence of DDs remained consistent across subgroups. Additionally, there was a J-shaped correlation between the WWI and the prevalence of DDs in children ages 6 through 11.ConclusionChildren 6–17 years of age with a high WWI were at greater risk for DDs; however, the causal relationships and potential mechanisms require further exploration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study

Li,

Zhou

2024

Front. Endocrinol.

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“…After excluding contraindications to the treatment and providing training to the parents for the subcutaneous administration of IFG-1, a progressive dosage, aiming for 0.12 mg per kilogram per day, was initiated. Dose was selected following all available information including the recently published pilot study with 9 patients with PMS [6] . Regular endocrinologist controls following standard guidelines for the monitoring of the use of IGF-1 [9] were conducted throughout the course of the treatment, including glycemia monitoring, IGF-1 levels, and echocardiography.…”

Section: Methodsmentioning

confidence: 99%

“…Preclinical studies with murine and human neuronal models of SHANK3 deficiency suggested that IGF-1 can reverse synaptic and motor learning deficits. Following this evidence, a pilot 3-month controlled trial of IGF-1 in 9 children with PMS was conducted to assess its effect on social function and repetitive behaviors [6] . A significant improvement in both social and repetitive difficulties was reported, with good tolerance.…”

Section: Introductionmentioning

confidence: 99%

Long-term treatment with insulin-like growth factor-1 in Phelan-McDermid syndrome: a case report

Parellada,

Burdeus-Olavarrieta,

Fraguas

et al. 2024

Rare Dis Orphan Drugs J

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Phelan-McDermid syndrome (PMS) is a chromosomal microdeletion syndrome generally caused by loss-of-function variants or deletions affecting the SHANK3 gene. We report on a case of a 19-year-old woman with a diagnosis of PMS, autism, and developmental disability. She has been under clinical care since the age of 9 and received treatment with subcutaneous IGF-1 from 11 to 15 years of age. The treatment spanned 2 periods, totaling 35 months, interspersed with a 16-month off-treatment interval. Clinically significant improvement was evident during the treatment periods, particularly in the Social Responsiveness Scale, the Aberrant Behavior Checklist, and clinical assessments, contrasted with a clear deterioration during the off-treatment period. Sleep difficulties worsened during the first period, and EKG repolarization abnormalities emerged during the second period, ultimately leading to definitive treatment discontinuation. In conclusion, an experimental long-term on-off-on treatment with IGF-1 in an adolescent with PMS resulted in mixed results, showcasing positive clinical improvements alongside potentially severe adverse events in the long run.

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Introduction to Exosome and Its Role in Brain Disorders

Sharma,

Rachamalla,

Mishra

et al. 2024

Exosomes Based Drug Delivery Strategies for Brain Disorders

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The role of insulin/IGF1 signalling in neurodevelopmental and neuropsychiatric disorders – Evidence from human neuronal cell models

Cited by 7 publications

References 190 publications

Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study

Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study

Long-term treatment with insulin-like growth factor-1 in Phelan-McDermid syndrome: a case report

Introduction to Exosome and Its Role in Brain Disorders

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