Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.
OBJECTIVE
To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs).


METHODS
In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein.


RESULTS
The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses.


CONCLUSIONS
Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment.
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Electronic address: srisawasdiP@yahoo.com.
Pornpen
P
Srisawasdi
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Bangkok 10400, Thailand.
Natchaya
N
Vanwong
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Bangkok 10400, Thailand.
Yaowaluck
Y
Hongkaew
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Bangkok 10400, Thailand.
Apichaya
A
Puangpetch
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Somlak
S
Vanavanan
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Boontarika
B
Intachak
Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, Samutprakarn 10270, Thailand.
Nattawat
N
Ngamsamut
Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, Samutprakarn 10270, Thailand.
Penkhae
P
Limsila
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Bangkok 10400, Thailand.
Chonlaphat
C
Sukasem
Quest Diagnostics, 3 Giralda Farms, Madison, NJ 07940, USA.
Martin H
MH
Kroll
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001321:Autistic Disorder / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000819:agonists* / Q000097:blood*; D008297:Male; D008991:Monitoring, Physiologic; D011388:Prolactin / Q000097:blood; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects
C499918:ADIPOQ protein, human; D052242:Adiponectin; D014150:Antipsychotic Agents; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011388:Prolactin; D002097:C-Reactive Protein; D018967:Risperidone; D006854:Hydrocortisone
Adolescent; Autistic spectrum disorders; Children; Diabetes; Metabolic risk factors; Risperidone