Elsevier

Brain and Development

Volume 26, Issue 5, August 2004, Pages 292-295
Brain and Development

Original article
Serum neurotrophin concentrations in autism and mental retardation: a pilot study

https://doi.org/10.1016/S0387-7604(03)00168-2Get rights and content

Abstract

To evaluate the availability of the serum neurotrophins for the diagnosis of the patients with neurodevelopmental disorder, we measured the serum concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in the patients diagnosed with autism (n=18) and mental retardation (n=20), or healthy controls (n=16), using enzyme-linked immunosorbent assay. There tended to be a higher concentration of serum BDNF found in the autistic group (P<0.05 by analysis of variance (ANOVA)) and the mental retardation group (P<0.001 by ANOVA) compared to the control group. Serum NT-4 concentration tended to be increased in the mental retardation group (P<0.05 by ANOVA). We conclude that measuring the serum concentration of two neurotrophins, BDNF and NT-4, might be helpful to diagnose or classify disorders such as autism or mental retardation.

Introduction

The importance of early intensive intervention to children with autism or mental retardation disorders (MR) has been widely perceived [1]. Although many of the cases are usually recognized or suspected in as early as the first 2–3 years of life, the final diagnoses and following behavioral intervention may often be delayed until the children reach school age, because of the difficulty to evaluate their social activity and communication.

Therefore, an establishment of reliable sub-diagnostic biochemical markers for these diseases has been considered as a prerequisite and urgent task. Until now, hyperserotonemia [2], low tetrahydrobiopterin [3], high γ-aminobutyric acid (GABA) concentration [4], and genetic linkage [5] were suspected for a relation with autism or MR and were investigated intensively; however, the results turned out to be equivocal.

A recent retrospective study by Nelson et al. [6] showed higher neonatal blood concentration of two neurotrophins (brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5)) as well as two neuropeptides (calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP)) in the subjects who were subsequently diagnosed with autism or MR, compared with the control subjects. The study is suggestive of the potentiality of these substances’ usefulness as sub-diagnostic biological markers of autism and MR.

BDNF and NT-4/5 belong to the neurotrophin family, which is widely expressed in the developing brain and is known to regulate neuronal cell survival, differentiation, and plasticity [7]. Moreover, a recent study showed that BDNF and NT4/5 themselves up-regulate the mRNA expression of BDNF through the glutamate receptor pathway [8], which suggested the close relation between these two factors.

We, therefore, chose the serum enzyme-linked immunosorbent assay (ELISA) quantification method to examine whether the concentrations of the serum neurotrophins, BDNF and/or NT-4/5, are suitable as supportive diagnostic markers along with the conventional behavioral diagnostic criteria to segregate the autism and MR patients from the control subjects in the Japanese population.

Section snippets

Subjects and methods

The study design was approved by the Ethical Committee of University of Tsukuba and Koshigaya Hospital, Dokkyo University School of Medicine, before the study began. Patients from the pediatric neuropsychiatry outpatient clinic of Koshigaya Hospital, Dokkyo University School of Medicine were enrolled in the study. Informed consent was obtained from the patients and/or their legal guardians in written form prior to the sample collection. Control samples were obtained from the healthy volunteers.

Results

The clinical features of the patients enrolled in this study were described in Table 1. Sixteen controls (five males, 11 females, age 22–24, mean 23.3 years), 18 autism patients (17 males, one female, age 3–27, mean 7.6 years), and 20 MR patients (11 males, nine females, age 1–20, mean 11 years) were enrolled in the study. The diagnosis was made by a child psychiatrist in accordance with the Diagnostic and Statistical Manual of Mental Disorders revised edition 4 (DSM-IV) [9]. Among the children

Discussion

In the present study, we presented a pilot investigation of the measurement of two serum neurotrophins, BDNF and NT-4/5, of those patients diagnosed with autism or MR.

Although there were some overlaps between values for patients and controls, statistical analyses revealed that there are significant differences in values of control BDNF vs. autism BDNF, control BDNF vs. MR BDNF, and control NT-4 vs. MR NT-4. This suggests that BDNF and NT-4 can segregate the autism and MR patients from the

Acknowledgements

This work is supported by grants-in-aid from the Japan Society for the Promotion of Science, the Naito Foundation, the Takeda Foundation, and Special Coordination Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. We express our sincere regret over the death of Dr. Nobuo Okado.

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