The World Journal of Biological Psychiatry ISSN: 1562-2975 (Print) 1814-1412 (Online) Journal homepage: http://www.tandfonline.com/loi/iwbp20 Biomarkers for attention-deficit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD Johannes Thome, Ann-Christine Ehlis, Andreas J. Fallgatter, Kerstin Krauel, Klaus W. Lange, Peter Riederer, Marcel Romanos, Regina Taurines, Oliver Tucha, Marat Uzbekov & Manfred Gerlach To cite this article: Johannes Thome, Ann-Christine Ehlis, Andreas J. Fallgatter, Kerstin Krauel, Klaus W. Lange, Peter Riederer, Marcel Romanos, Regina Taurines, Oliver Tucha, Marat Uzbekov & Manfred Gerlach (2012) Biomarkers for attention-deficit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD, The World Journal of Biological Psychiatry, 13:5, 379-400, DOI: 10.3109/15622975.2012.690535 To link to this article: http://dx.doi.org/10.3109/15622975.2012.690535 Published online: 27 Jul 2012. Submit your article to this journal Article views: 470 View related articles Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iwbp20 Download by: [Bibliothek der MedUniWien], [Professor Siegfried Kasper] Date: 25 May 2016, At: 02:36 The World Journal of Biological Psychiatry, 2012; 13: 379–400 ORIGINAL INVESTIGATION Biomarkers for attention-defi cit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD JOHANNES THOME 1,2 , ANN-CHRISTINE EHLIS 3 , ANDREAS J. FALLGATTER 3 , KERSTIN KRAUEL 4 , KLAUS W. LANGE 5 , PETER RIEDERER 6 , MARCEL ROMANOS 7 , REGINA TAURINES 8 , OLIVER TUCHA 9 , MARAT UZBEKOV 10 & MANFRED GERLACH 8 1 Department of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany, 2 College of Medicine, Swansea University, Swansea, UK, 3 Department of Psychiatry and Psychotherapy, University of T ü bingen, Tü bingen, Germany, 4 Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Magdeburg, Magdeburg, Germany, 5 Department of Experimental Psychology, University of Regensburg, Regensburg, Germany, 6 Department for Psychiatry, Psychosomatics and Psychotherapy, University of Wü rzburg, Wü rzburg, Germany, 7 Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Munich, Munich, Germany, 8 Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wü rzburg, Wü rzburg, Germany, 9 Department of Clinical and Developmental Neuropsychology, Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, The Netherlands, and 10 Department of Brain Pathology, Research Institute of Psychiatry, Moscow, Russia Abstract Objective. Psychiatric “ nosology ” is largely based on clinical phenomenology using convention-based diagnostic systems not necessarily refl ecting neurobiological pathomechanisms. While progress has been made regarding its molecular biology and neuropathology, the phenotypic characterization of ADHD has not improved. Thus, validated biomarkers, more directly linked to the underlying pathology, could constitute an objective measure for the condition. Method. The task force on biological markers of the World Federation of Societies of Biological Psychiatry (WFSBP) and the World Federation of ADHD commissioned this paper to develop a consensus report on potential biomarkers of ADHD. The criteria for biomarker-candidate evaluation were: (1) sensitivity Ͼ 80%, (2) specifi city Ͼ 80%, (3) the candidate is reliable, reproduc- ible, inexpensive, non-invasive, easy to use, and (4) confi rmed by at least two independent studies in peer-reviewed journals conducted by qualifi ed investigators. Results. No reliable ADHD biomarker has been described to date, but some promis- ing candidates (e.g., olfactory sensitivity, substantial echogenicity) exist. A problem in the development of ADHD markers is sample heterogeneity due to aetiological and phenotypic complexity and age-dependent co-morbidities. Conclusions. Most likely, no single ADHD biomarker can be identifi ed. However, the use of a combination of markers may help to reduce heterogeneity and to identify homogeneous subtypes of ADHD. Key words: Biomarker , attentention-defi cit/hyperactivity disorder , olfaction , transcranial echosonography , neuroimaging , proteomics Downloaded by [Bibliothek der MedUniWien], [Professor Siegfried Kasper] at 02:36 25 May 2016 Introduction (Polanczyk et al. 2007). Epidemiological studies Attention-defi cit/hyperactivity disorder (ADHD) is have shown that ADHD can persist into adulthood one of the most prevalent psychiatric disorders in (reviewed by Biederman and Faraone 2005). There children and adolescents and characterized by the tends to be an age-dependent decline in symptoms, core symptoms of age-inappropriate levels of inatten- but even if symptoms are not suffi ciently prominent tion, hyperactivity and impulsivity (Taylor et al. to prompt a diagnosis, they are frequently associated 2004; Biederman and Faraone 2005). The condition with signifi cant clinical problems (ibid.). Thus, affects approximately 5% of children worldwide although most individuals with childhood ADHD Correspondence: Johannes Thome, MD, PhD, Professor of Psychiatry, Department of Psychiatry, University of Rostock, Gehlsheimer Stra ß e 20, 18147 Rostock, Germany. E-mail: [email protected] (Received 21 March 2012 ; accepted 23 April 2012 ) ISSN 1562-2975 print/ISSN 1814-1412 online © 2012 Informa Healthcare DOI: 10.3109/15622975.2012.690535 380 J. Thome et al. will no longer meet the full threshold criteria for the individual effect on the increasing vulnerability to disorder by the age of 30– 40 years, approximately the disorder and leading to different pathophysiolog- half of them will exhibit ongoing psychosocial impair- ical pathways (Biederman and Faraone 2005; Thome ment consistent with the DSM-IV diagnosis of and Reddy 2009). This multi-factorial and multi- “ ADHD in partial remission ” , suggesting that many pathway view of ADHD is consistent with the observed still will require treatment. heterogeneity from genetics to behaviour. Despite widespread public scepticism regarding ADHD is a highly heritable disease, with estimated the legitimacy of ADHD as a valid psychiatric dis- heritability rates of up to 80% (e.g., Levy et al. 1997; order (Buitelaar and Rothenberger 2004; Faraone Freitag et al. 2010). Results from molecular genetic 2005), several recent fi ndings demonstrate the valid- studies indicate a complex genetic architecture of ity of the diagnosis with biological underpinnings ADHD, i.e. genetic vulnerability is mediated by a such as multiple genetic factors, ADHD-related dif- multitude of risk genes with small individual effects ferences in brain structure and function, and changes (Faraone et al. 2005). In order to gain more insight in neurotransmission especially in the basal ganglia into the mechanisms leading from a genetic/biological thalamocortical neurocircuitries (see Biederman and basis of the disease to the full clinical phenotype, Faraone 2005; Konrad et al. 2006; Mehler-Wex intermediate phenotypes (so-called “ endophenotypes ” ) et al. 2006; Volkow et al. 2007; Albayrak et al. 2008; have proven to be useful mediators. Endophenotypes Gerlach et al. 2008a; Thome and Reddy 2009). are assumed to be more closely linked to the relevant The diagnosis of ADHD requires the identifi ca- underlying psycho- or neuropathology, i.e. aetiolog- tion of specifi c behaviours that meet international ical factors, than categorical clinical diagnoses. They diagnostic criteria as delineated in the Diagnostic are also usually less complex, and therefore more and Statistical Manual of Mental Disorders (DSM- readily assessable, than diverse clinical phenotypes. IV-R; American Psychiatric Association 1992). Different neuropsychological variables have been Other criteria include those of the International considered as putative endophenotypes of ADHD, Statistical Classifi cation of Diseases and Related Health and more recently, functional imaging methods and Problems (ICD-10; World Health Organization 1992) neurophysiological techniques have been used to which allows the diagnosis of “ hyperkinetic disor- establish corresponding markers grounded in neuro- der ” , basically a more severe and “ refi ned ” subset science (Castellanos and Tannock 2002; Gould and of DSM-IV ADHD. Manji 2004). Evidence from both clinical and epidemiological A biomarker (or biological marker) is defi ned as a studies demonstrates that children with ADHD are characteristic that can be “ objectively ” measured at higher risk for other psychiatric and substance use and evaluated as an indicator of normal biological disorders (Biederman and Faraone 2005). Common processes, pathogenetic processes or pharmacologic co-morbidities in children and adolescents include responses to a therapeutic intervention (Biomarkers oppositional defi ant disorder and conduct disorder, Defi nitions Working Group 2001). According to the anxiety disorders, mood disorders, tic disorders, type of information that they provide, biomarkers for motor coordination disorder, learning disabilities CNS disorders can be classifi ed as clinical, neuroim- and problems in reciprocal social interaction and aging, biochemical, genetic or proteomic