Decreased serum levels of adiponectin in subjects with autism

Abstract

The neurobiological basis for autism remains poorly understood. We hypothesized that adipokines, such as adiponectin, may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of adiponectin are altered in subjects with autism. We measured serum levels of adiponectin in male subjects with autism (n = 31) and age-matched healthy male subjects (n = 31). The serum levels of adiponectin in the subjects with autism were significantly lower than that of normal control subjects. The serum adiponectin levels in the subjects with autism were negatively correlated with their domain A scores in the Autism Diagnostic Interview—Revised, which reflects their impairments in social interaction. This study suggests that decreased levels of serum adiponectin might be implicated in the pathophysiology of autism.

Introduction

Autism is a neurodevelopmental disorder resulting in pervasive abnormalities in social interaction and communication, repetitive behaviors, and restricted interests. Although the precise mechanism underlying the pathophysiology of autism remains to be determined, accumulating evidence suggests that the abnormality of inflammatory events may be implicated in the pathophysiology of autism (Licinio et al., 2002, Cohly & Panja, 2005, Pardo et al., 2005, Okada et al., 2007, Tsuchiya et al., 2007).

Adiponectin is a recently discovered protein that is produced by adipose tissue, circulates in high concentrations in the peripheral blood, and involved in the control of energy metabolism (Kadowaki and Yamauchi, 2005). Its plasma levels are inversely correlated with insulin resistance and parameters of obesity such as body mass index (BMI) (Maeda et al., 2002, Spranger et al., 2003, Weiss et al., 2004). Adiponectin belong to adipokines, which consist of biologically active substances found in adipocytes of white adipose tissue (Pan and Kastin, 2007). Many adipokines exert pro-inflammatory effects and may be causally involved in obesity and diabetes. These include leptin, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), plasminogen activator inhibitor-1, angiotensinogen, and resistin. A few others, particularly transforming growth factor beta-1 (TGF-β1) and adiponectin, are anti-inflammatory and may exert protective functions against metabolic disturbance. Interestingly, some of pro-inflammatory adipokines are implicated in the pathophysiology of autism. For instance, children with autism had significantly higher plasma leptin levels compared with typically developed controls (Ashwood et al., 2008). Lipopolysaccharide-stimulated productions of TNF-α and IL-6 were greater in peripheral blood mononuclear cells from patients with autism spectrum disorder than those from controls (Jyonouchi et al., 2001). Postmortem study showed that protein levels of TNF-α and IL-6 were significantly increased in the brains of patients with autism spectrum disorder compared with controls (Li et al., 2009). In contrast, anti-inflammatory adipokine TGF-β1 has shown to be decreased in serum (Okada et al., 2007) as well as plasma (Ashwood et al., 2008) in subjects with autism. These findings suggest that the inflammatory events in autism may be inappropriately regulated (Pardo et al., 2005) due to enhanced responses of pro-inflammatory adipokines, such as TNF-α and IL-6, and to reduced anti-inflammatory adipokine, TGF-β1. Furthermore, concerning treatment, thiazolidinedione, which exert anti-inflammatory effects in glial cells is currently being tested in clinical trials of autistic disorder (Boris et al., 2007).

At present, no studies demonstrating alterations in the adiponectin in autism have been reported. Considering the anti-inflammatory function of adiponectin, we hypothesized that peripheral adiponectin levels may be reduced in subjects with autism. To test this, we examined serum levels of adiponectin in subjects with autism in comparison with age-matched control subjects. Furthermore, we also examined any relationship between serum levels of adiponectin and clinical variables in autistic patients.