Foreword
Potential biomarkers of autism “
I hope that the bringing together of these different research avenues will encourage interesting discussion and debate regarding the future of biomarker research in autism.
”
Autism is a complex, life-long neurodevelop mental disorder characterized by impairments in communication, relation to others and behavioral flexibility. In 2012, a systematic review considering data from several countries and studies estimated a median autism prevalence of 17 per 10,000 individuals [1] . Diagnosis of autistic spectrum disorders is currently phenotype based with no trusted laboratory test available to aid clinicians. Some tools have been developed to help with the diagnosis of autism [2] ; however, the desire for clinically useful and reliable biomarkers remains strong. Autism is known to have a strong genetic component, but, despite numerous studies discovering genetic associations, a complete genetic explanation for the disorder remains elusive and reliable genetic markers have not yet been identified [3] . In addition, a number of nongenetic potential markers have been identified but have failed to be translated into screening tests. The themed articles in this issue of Biomarkers in Medicine aim to frame the discussion of the current progress towards the identification of biomarkers of autism. The first article in this issue, an editorial article by Steinman et al., discusses potential umbilical cord biomarkers, including IGF, serotonin and anti-MBP [4] . Previous studies have documented that IGF is essential for the myelination of developing fetal neurons; this is in addition to the well-known links between IGF, maternal inflammation, infection and autism supporting IGF as a potential marker. IGF is currently being investigated in prospective studies [4] . The article concludes by discussing how combin-
10.2217/BMM.14.21 © 2014 Future Medicine Ltd
ing IGF data with data regarding levels of the known markers, serotonin and anti-MBP, in order to calculate an autism index, could provide a new diagnostic method for at-risk neonates [4] . Due to their links with serotonin, tryptophan metabolism pathways are also being studied in autistic patients, where there is growing evidence that these function abnormally. The editorial in this issue by Schwartz highlights some of the research to date regarding impaired tryptophan metabolism and discusses the relevance to autistic patients [3] . It is hoped that findings related to this aberrant metabolism will provide an etiological insight into the disorder, in addition to potentially developing a reliable screening test. Known links between tryptophan metabolism pathways and mito chondrial dysfunction, serotonin and melatonin are also discussed in this article in relation to their potential implications in autism. The systems discussed by Schwartz are not the only pathways known to be altered in autism. The first review article in this themed section focuses on various aspects of the metabolic pathology of autism [5] . Disruptions to multiple pathophysiological systems, including redox, folate, methylation and mitochondrial metabolism, have been well documented in autistic patients. This review discusses these pathways and their pathologies in autism and continues to discuss treatments targeted to these abnormalities in addition to the potential for developing suitable biomarkers of these aberrant metabolic pathways. Gastrointestinal (GI) disturbances have been extensively documented in individuals with autism. In this issue, the review by
Biomarkers Med. (2014) 8(3), 311–312
Hannah Wilson Future Medicine Ltd., Unitec House, 2 Albert Place, London, N3 1QB, UK [email protected]
part of
ISSN 1752-0363
311
Foreword Potential biomarkers of autism Wang et al. examines this associated pathology with a particular focus on the growing potential of GI microbiota biomarkers in addition to markers of altered bacterial fermentation in the GI tract [6] . The review discusses gut Clostridia, Bacteroides, Bifidobacteria and Akkermansia spp, levels of which have been observed to be abnormal in individuals with autism. In addition, the authors also discuss gut fermentation products including short-chain fatty acids, ammonia and p-cresol. Wang et al. conclude with the hope that these factors may be potential biomarkers for the identification of autistic children at risk of GI disturbance, thus allowing for the development and use of tailored interventions.
“...maternal infection and inflammation have known links with autism. Autoimmunity has therefore been a well-studied area of autism research in recent years...
”
As mentioned earlier, maternal infection and inflammation have known links with autism. Auto immunity has therefore been a well-studied area of autism research in recent years and this topic is reviewed in this issue by Elamin et al. Autoantibodies have the ability to cross the blood–brain barrier and combine with antigens to create immune complexes capable of damaging neurological tissue [7] . In their review, Elamin et al. examine the potential of using autoantibodies as novel biomarkers for autism, in addiReferences 1
2
312
Elsabbagh M, Divan G, Koh YJ et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5(3), 160–179 (2012). Zânder E, Sturm H, Bölte S. The added value of the combined use of the Autism Diagnostic Interview–Revised and the Autism Diagnostic Observation Schedule: diagnostic validity in a clinical Swedish sample of toddlers and young preschoolers. Autism doi:10.1177/1362361313516199 (2014) (Epub ahead of print).
tion to providing insights into the neurodevelopmental processes that lead to autism. Taking a different approach, the final review in this themed section discusses γ-band abnormalities, as observed on EEGs and MEGs, as potential biomarkers of autism [8] . γ-band responses can be measured using a variety of noninvasive techniques and these oscillations have been documented as abnormal in studies of autistic patients [9] . Rojas et al. discuss studies using various stimuli in autistic individuals and unaffected first-degree relatives [8] . Associations between γ-band abnormalities and clinical severity are also discussed with a view towards their use as both predictors of diagnosis and surrogate markers in clinical trials of new interventions. In summary, the articles highlighted in this issue of Biomarkers in Medicine give a broad view of the on going research into potential markers of autism. I hope that the bringing together of these different research avenues will encourage interesting discussion and debate regarding the future of biomarker research in autism. Financial & competing interests disclosure H Wilson is an employee of Future Medicine Ltd. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. 5
Frye RE, James SJ. Metabolic pathology of autism in relation to redox metabolism. Biomarkers Med. 8(3), 321–330 (2014).
6
Wang L, Conlon MA, Christophersen CT, Sorich MJ, Angley MT. Gastrointestinal microbiota and metabolite biomarkers in children with autism spectrum disorders. Biomarkers Med. 8(3), 331–344 (2014).
7
Elamin NE, AL-Ayadhi LY. Brain autoantibodies in autism spectrum disorders. Biomarkers Med. 8(3), 345–352 (2014).
3
Schwartz C. Aberrant tryptophan metabolism: the unifying biochemical basis for autism spectrum disorders? Biomarkers Med. 8(3), 313–315 (2014).
8
Rojas DC, Wilson LB. Gamma-band abnormalities as markers of autism spectrum disorders. Biomarkers Med. 8(3), 353–368 (2014).
4
Steinman G, Mankuta D. Umbilical cord biomarkers in autism determination. Biomarkers Med. 8(3), 317–319 (2014).
9
Orekhova EV, Stroganova TA, Nygren G et al. Excess of high frequency electroencephalogram oscillations in boys with autism. Biol. Psychiatry 62(9), 1022–1029 (2007).
Biomarkers Med. (2014) 8(3)
future science group
Potential biomarkers of autism “
I hope that the bringing together of these different research avenues will encourage interesting discussion and debate regarding the future of biomarker research in autism.
”
Autism is a complex, life-long neurodevelop mental disorder characterized by impairments in communication, relation to others and behavioral flexibility. In 2012, a systematic review considering data from several countries and studies estimated a median autism prevalence of 17 per 10,000 individuals [1] . Diagnosis of autistic spectrum disorders is currently phenotype based with no trusted laboratory test available to aid clinicians. Some tools have been developed to help with the diagnosis of autism [2] ; however, the desire for clinically useful and reliable biomarkers remains strong. Autism is known to have a strong genetic component, but, despite numerous studies discovering genetic associations, a complete genetic explanation for the disorder remains elusive and reliable genetic markers have not yet been identified [3] . In addition, a number of nongenetic potential markers have been identified but have failed to be translated into screening tests. The themed articles in this issue of Biomarkers in Medicine aim to frame the discussion of the current progress towards the identification of biomarkers of autism. The first article in this issue, an editorial article by Steinman et al., discusses potential umbilical cord biomarkers, including IGF, serotonin and anti-MBP [4] . Previous studies have documented that IGF is essential for the myelination of developing fetal neurons; this is in addition to the well-known links between IGF, maternal inflammation, infection and autism supporting IGF as a potential marker. IGF is currently being investigated in prospective studies [4] . The article concludes by discussing how combin-
10.2217/BMM.14.21 © 2014 Future Medicine Ltd
ing IGF data with data regarding levels of the known markers, serotonin and anti-MBP, in order to calculate an autism index, could provide a new diagnostic method for at-risk neonates [4] . Due to their links with serotonin, tryptophan metabolism pathways are also being studied in autistic patients, where there is growing evidence that these function abnormally. The editorial in this issue by Schwartz highlights some of the research to date regarding impaired tryptophan metabolism and discusses the relevance to autistic patients [3] . It is hoped that findings related to this aberrant metabolism will provide an etiological insight into the disorder, in addition to potentially developing a reliable screening test. Known links between tryptophan metabolism pathways and mito chondrial dysfunction, serotonin and melatonin are also discussed in this article in relation to their potential implications in autism. The systems discussed by Schwartz are not the only pathways known to be altered in autism. The first review article in this themed section focuses on various aspects of the metabolic pathology of autism [5] . Disruptions to multiple pathophysiological systems, including redox, folate, methylation and mitochondrial metabolism, have been well documented in autistic patients. This review discusses these pathways and their pathologies in autism and continues to discuss treatments targeted to these abnormalities in addition to the potential for developing suitable biomarkers of these aberrant metabolic pathways. Gastrointestinal (GI) disturbances have been extensively documented in individuals with autism. In this issue, the review by
Biomarkers Med. (2014) 8(3), 311–312
Hannah Wilson Future Medicine Ltd., Unitec House, 2 Albert Place, London, N3 1QB, UK [email protected]
part of
ISSN 1752-0363
311
Foreword Potential biomarkers of autism Wang et al. examines this associated pathology with a particular focus on the growing potential of GI microbiota biomarkers in addition to markers of altered bacterial fermentation in the GI tract [6] . The review discusses gut Clostridia, Bacteroides, Bifidobacteria and Akkermansia spp, levels of which have been observed to be abnormal in individuals with autism. In addition, the authors also discuss gut fermentation products including short-chain fatty acids, ammonia and p-cresol. Wang et al. conclude with the hope that these factors may be potential biomarkers for the identification of autistic children at risk of GI disturbance, thus allowing for the development and use of tailored interventions.
“...maternal infection and inflammation have known links with autism. Autoimmunity has therefore been a well-studied area of autism research in recent years...
”
As mentioned earlier, maternal infection and inflammation have known links with autism. Auto immunity has therefore been a well-studied area of autism research in recent years and this topic is reviewed in this issue by Elamin et al. Autoantibodies have the ability to cross the blood–brain barrier and combine with antigens to create immune complexes capable of damaging neurological tissue [7] . In their review, Elamin et al. examine the potential of using autoantibodies as novel biomarkers for autism, in addiReferences 1
2
312
Elsabbagh M, Divan G, Koh YJ et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5(3), 160–179 (2012). Zânder E, Sturm H, Bölte S. The added value of the combined use of the Autism Diagnostic Interview–Revised and the Autism Diagnostic Observation Schedule: diagnostic validity in a clinical Swedish sample of toddlers and young preschoolers. Autism doi:10.1177/1362361313516199 (2014) (Epub ahead of print).
tion to providing insights into the neurodevelopmental processes that lead to autism. Taking a different approach, the final review in this themed section discusses γ-band abnormalities, as observed on EEGs and MEGs, as potential biomarkers of autism [8] . γ-band responses can be measured using a variety of noninvasive techniques and these oscillations have been documented as abnormal in studies of autistic patients [9] . Rojas et al. discuss studies using various stimuli in autistic individuals and unaffected first-degree relatives [8] . Associations between γ-band abnormalities and clinical severity are also discussed with a view towards their use as both predictors of diagnosis and surrogate markers in clinical trials of new interventions. In summary, the articles highlighted in this issue of Biomarkers in Medicine give a broad view of the on going research into potential markers of autism. I hope that the bringing together of these different research avenues will encourage interesting discussion and debate regarding the future of biomarker research in autism. Financial & competing interests disclosure H Wilson is an employee of Future Medicine Ltd. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. 5
Frye RE, James SJ. Metabolic pathology of autism in relation to redox metabolism. Biomarkers Med. 8(3), 321–330 (2014).
6
Wang L, Conlon MA, Christophersen CT, Sorich MJ, Angley MT. Gastrointestinal microbiota and metabolite biomarkers in children with autism spectrum disorders. Biomarkers Med. 8(3), 331–344 (2014).
7
Elamin NE, AL-Ayadhi LY. Brain autoantibodies in autism spectrum disorders. Biomarkers Med. 8(3), 345–352 (2014).
3
Schwartz C. Aberrant tryptophan metabolism: the unifying biochemical basis for autism spectrum disorders? Biomarkers Med. 8(3), 313–315 (2014).
8
Rojas DC, Wilson LB. Gamma-band abnormalities as markers of autism spectrum disorders. Biomarkers Med. 8(3), 353–368 (2014).
4
Steinman G, Mankuta D. Umbilical cord biomarkers in autism determination. Biomarkers Med. 8(3), 317–319 (2014).
9
Orekhova EV, Stroganova TA, Nygren G et al. Excess of high frequency electroencephalogram oscillations in boys with autism. Biol. Psychiatry 62(9), 1022–1029 (2007).
Biomarkers Med. (2014) 8(3)
future science group
