Potential Biomarkers in Studying Autism and Other Neurodevelopmental Disorders

Potential Biomarkers in Studying Autism and Other Neurodevelopmental Disorders

Bertoglio Kiah C, Hendren Robert L

US Psychiatry 2009;2(1):48-53

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Abstract
Growing evidence suggests that autism is a syndrome with a number of etiologies and different mechanisms that lead to abnormal development. This article highlights the pressing need to identify autism subgroups with differing etiologies and underlying mechanisms as they may each require different approaches for prevention or treatment. This article proposes a shift in the way research for autism is traditionally conceptualized, toward a focus on translational, mechanism-driven research. By targeting treatments to specific mechanisms and assessing whether changes in biomarkers correspond with changes in behavior, we can advance our understanding of how to classify and treat the various autism subgroups. The use of biomarkers that point to specific mechanisms of disease will help to identify meaningful subtypes of autism and will help tailor the treatment or prevention strategy to each mechanism. This empirical but mechanistically driven approach has the goal of rapidly alleviating or preventing symptoms even if the cause or causes of autism remain unknown for some time.

Keywords
Autism, biomarkers, treatment, research, neurodevelopmental disorders

Disclosure: Kiah C Bertoglio, BS, has no conflicts of interest to declare. Robert L Hendren, DO, has received research grants from Pfizer Inc., Forest Pharmaceuticals Inc., AstraZeneca, Otsuka America Pharmaceutical Inc., Bristol Meyer Squibb, Neuropharm, LTD, Janssen, Autism Speaks, and the National Institute of Mental Health (NIMH).
Received: April 5, 2008 Accepted: June 8, 2008
Correspondence: Robert L Hendren, DO, The Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis Medical Center, 2825 50th Street, Sacramento, CA 95817. E: rlhendren@ucdavis.edu

Autism is a complex neurodevelopmental disorder characterized by impairments in communication, social interaction, and repetitive behaviors. The pathogenesis of autism is thought to involve an interaction between multiple and variable susceptibility genes, epigenetic effects, and environmental factors. The large spectrum of symptom severity, diverse laboratory profiles, varying associated symptoms, and inconsistent response to treatment across individuals with autism strongly supports the presence of mechanistic subgroups within the current diagnosis of autism, each of which may have a different etiology and response to treatment. However, despite extensive research, these subgroups have not yet been clearly defined.

A paradigm shift is occurring in how we understand and develop treatment targets for neurodevelopmental disorders. We once thought of disorders as based on externally manifested symptoms or on a single finding of pathology, for instance characterizing autism as a disorder of socialization or as a brain disorder. Based in part on what is being learned about metabolic mechanisms such as oxidative stress and immune function leading to disordered functioning associated with diseases such as cancer, we are beginning to discover that abnormal metabolic whole-body mechanisms are also involved in autism and other developmental disorders. A more productive way of characterizing these epigenetic mechanisms that go from DNA to surface symptoms might be as layers in the Earth’s crust, with DNA at the core, proceeding to messenger RNA (mRNA), cell modulation, physiological processes, neuromodulators, brain structure, cognition, and, finally, externally observable behavioral symptoms (see Figure 1). The epigenetic translation of genetic vulnerability and environmental stresses into the disorder may prove useful in identifying subtypes of neurodevelopmental disorders as well as biomarkers, leading to more specific and effective treatment targets. Successful treatment targets may interact with and ameliorate other pathophysiological processes within the body’s epigenetic layers, producing a domino effect that may alter processes from gene expression through behavioral symptoms.

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