Biomarkers for neurodevelopmental disorders

Abstract

Background: Much progress has been made in the ubiquitous recognition of attention deficit hyperactivity/hyperkinetic disorder (ADHKD) as a distinct neuro-pathological entity, yet its full biological underpinnings have not yet been fully elucidated. Although most therapeutic agents appear to exert a dopaminergic effect, certain clinical diagnostic features are considered to be related to serotonergic function. This can lead to, at times, a lack of clarity around both diagnosis and treatment. A recognised association exists between AD-HKD and Autistic Spectrum Disorders, with both disorders recognised as having a neuro-developmental basis and a high degree of co-morbidity observed in clinical practice. Aims: This study is a case control study which furthers previous research measuring urinary 5-H1AA. Using validatedmethodology, this study will extend testing to AD-HKD children of both sexes and will include preliminary studies of childrenwith confirmedAutistic Spectrum Disorder. Urinary 5-H1AA levels, serotonin and dopamine will be measured in medicated and un-medicated subjects. We postulate that subjects withADHDandASDwill have altered levels of 5H1AAand that this biomarker will vary by sex and administration of stimulant medication. The ASD armof the study is exploratory in nature and focuses on the putative role of endocannabinoids and biomarkers of oxidative stress in ASD subjects and matched controls. Methods: A test group of 20 children with a confirmed diagnosis of AD-HKD attending child and adolescent mental health services were recruited together with an age and gender matched control group. 10 children with ASD were recruited to participate in the exploratory arm of the study. A mid stream urinary specimen was taken from all participants and analysed with a liquid chromatographic mass spectrometry assay. Results: Quantitative measurements were carried out for each of the potential markers in the urine samples collected. All quantitative measurements of urine sampleswere presented as a ratio of urinary creatinine concentration to correct for differences in kidney function.We previously identified 5-HIAA as a potential biomarker for AD-HKD and validated the analysis of serotonin, its keymetabolite hydroxyindole acetic acid (5- HIAA) and dopamine in urine using a nanoelectrospray-MSn method interfaced with an LTQ Orbitrap mass spectrometer. Statistical analysis indicates that 5-H1AA was significantly lower in the test population, in comparison to healthy controls (p<0.001).