Pathophysiology Linking Chronic Lead Exposure to Attention-Deficit/Hyperactive Disorder

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Pathophysiology Linking Chronic Lead Exposure to Attention-Deficit/Hyperactive Disorder

Introduction

Attention-deficit/hyperactive disorder (ADHD) is a condition commonly associated with inattentiveness, impulsiveness, and/or hyperactivity. Between five and ten percent of children are affected by the disorder, which often extends into adulthood (Scahill and Schwab-Stone 2000; Curatolo et al. 2010; Froehlich et al. 2011). The biological mechanisms and associated pathways responsible for ADHD are not entirely understood. Complex interactions between multiple genes estimate to contribute 60% to 80% toward development of the disorder, leaving a substantial portion up to environmental circumstances (Curatolo et al. 2010; Froehlich et al. 2011). From an environmental toxicology perspective, post-natal exposure to heavy metals and chemicals is of particular concern (Curatolo et al. 2010). Epidemiological studies have shown positive correlations between ADHD symptoms and exposure to toxins such as lead, manganese, phthalates and organophosphates in children (Bouchard et al. 2010; Nigg et al. 2010; Froehlich et al. 2011).

Due in part to the ambiguities surrounding ADHD causation, the pathophysiological evidence linking such contaminants as developmental factors is rather underdeveloped. Lead, for example, is the most well-established chemical risk factor (Froehlich et al. 2011). Yet current pathway models are far from comprehensive. In addition, of the many publications documenting mechanisms of lead-induced neurotoxicity, there are none, to my knowledge, which addresses the pathophysiology linking it to ADHD. This paper serves as an analytical review of proposed pathways and processes that may link lead exposure to increased risk of ADHD.

Overview of ADHD

Understanding the etiology of ADHD is critical in discerning how genetic and environmental factors might induce it. Diagnosis depends on a spread of behavioral symptoms - mainly excessive movement, impulsiveness and difficulties paying attention. The only way to know is a clinical, diagnostic assessment. The diagnostic evaluation happens by an interview with the patient or the parents where the symptoms and difficulties discussed. ADHD is diagnosed only if the symptoms have a practical impact. If this happens, the doctor, the patient and family must decide whether treatment is necessary and, if so, what kind. It is essential to evaluate the conditions and problems with a view to establishing an effective treatment plan and personalized ADHD classifies into three types: the inattentive type, the hyperactive/impulsive type, and a fusion of the two (Tripp and Wickens 2009; Curatolo et al. 2010). Variability in combinations and severity of symptoms, as well as the potential for bias in diagnosis, can make it difficult to identify phenotypic trends. However, distinguishing these subtle behavioral differences has enabled researchers to narrow down the multitude of pathophysiological possibilities to form more extensive, refined hypotheses.

Neuroimaging studies have been able to link behavioral and cognitive problems common to ADHD patients with deformities in the areas of the brain responsible for symptoms. The prefrontal cortex, basal ganglia, cingulate cortex and cerebellum, are among typically affected regions (Bush et al. 2005; Krain and Castellanos 2006; Curatolo et al. 2010). Together they make up the fronto-striato-cellebar network, or fronto-striatal network with the exclusion of the ...