Dr David Coghill

The Developmental Research Group’s research focuses on developmental psychiatric disorders in children.

Whilst the main focus is on understanding the various complexities that surround Attention Deficit Hyperactivity Disorder (ADHD), we are also interested in a range of other disorders Conduct Disorder, Depression and Autism Spectrum Disorders.

The Neuropsychology of ADHD

ADHD is a complex developmental psychiatric disorder that affects around 5% of school-age children. Hyperkinetic Disorder represents a severe pervasive and impairing form of ADHD that affects around 1.5% of UK children and young people. ADHD and HKD are highly heritable (h2 ≈ .74)) and convergent evidence has supported it having a strong neurobiological basis. Traditional models of ADHD attempted to explain the whole of ADHD as the consequence of a single pivotal neuropsychological deficit (e.g. inhibitory problems, intra-individual variability, delay aversion). Recent studies have focused on demonstrating deficits in executive functioning (higher order brain functions that include working memory, planning, inhibition and attentional set shifting) which arise as a consequence of altered frontostriatal dopaminergic neurotransmission. More recently our research and that of several other groups has challenged the single pathway models and have demonstrated ADHD to be extremely heterogeneous at the genetic, neurophysiological and neuropsychological levels of analysis. Various aspects of our research have supported, expanded and challenged the findings of others. By using a battery of tasks rooted in neuroscience (CANTAB) in a carefully selected and rigorously diagnosed group of previously drug treatment naïve boys with HKD we were able to avoid the design compromises inherent to many other studies. We were able to confirm that whilst as a group boys with HKD have significant neuropsychological deficits they are extremely heterogeneous with only a relatively small proportion of boys having a deficit on any one task. Whilst we were able to confirm the presence of deficits in executive functioning we also found significant deficits in several aspects of non-executive neuropsychological functioning. Most importantly we have found that boys with HKD and ADHD perform very poorly on several simple pattern recognition tasks that have been demonstrated to be primarily dependent on intact temporal lobe and amygdalo/hippocampal rather than frontostriatal functioning and on cholinergic rather than dopaminergic neurotransmission. Interestingly these boys performed as poorly on these tasks as did elderly subjects with Alzheimer’s Dementia in previous studies using the same task. Further data deconstructing the memory deficits in ADHD and investigating the relationships between all the key endophenotypes have been collected and are currently being analysed. These findings are relevant to both the pharmacological and psychological treatment of ADHD and we are currently engaged in studies to translate these findings from the lab to the clinic.

Pharmacological treatments of ADHD

ADHD is treated with both psychological and pharmacological therapies. When ADHD is severe pervasive and impairing drug treatments are considered to be the first line of treatment. Several medications have been demonstrated to be effective in reducing ADHD symptoms our group has been involved in running clinical trials for several of these including the psychostimulant methylphenidate, the non-stimulant atomoxetine and the amfetamine pro-drug lisdexamfetamine. Methylphenidate (often referred to by one of its trade names Ritalin) is the most commonly use medication for treating ADHD. Although press reports warning against the use of methylphenidate continue to appear the scientific evidence suggests that methylphenidate is both effective and safe. We have conducted the largest neuropsychopharmacological study to date into the effects of acute and chronic effects of methylphenidate on clinical and neuropsychological functioning in previously untreated boys with ADHD. Importantly although we found methylphenidate to improve performance on several, but not all, of the neuropsychological measures studied there was no evidence to suggest that methylphenidate impairs neuropsychological functioning. Contrary to predictions methylphenidate improved performance on several non-executive memory tasks whist not altering performance on a series of executive tasks. Interestingly we found that the strongest predictor of clinical response was pre-treatment performance on the Delayed Matching to Sample task of short term memory that was both the strongest predictor of ADHD and showed the largest response to medication. These findings have challenged the textbook view on how stimulants such as methylphenidate work and may lead to the development of new ADHD treatments and a more informed use of those currently used.

Whilst methylphenidate generally effective and safe, not everyone responds to the same degree, some are unable to tolerate this medication because of adverse effects. Very occasionally someone taking methylphenidate will die suddenly and although it is not clear whether such rare occurrences are related to the drug itself neither is it certain that they are not. Pharmacogenetic studies have the potential to address these questions. Methylphenidate is metabolised by a single enzyme. Carboxylesterase 1A (CES1A). Along with Professor Coughtrie's lab We have recently cloned the CES1A gene and two of its most common coding variants and demonstrated that the variants are less effective at metabolizing methylphenidate than the wild type. This would mean that those with either of these gene variants are likely to be less effective at clearing methylphenidate from their systems and that they may also be exposed to much higher levels during treatment with regular doses and may therefore be more at risk of certain adverse effects. Clinical studies are in progress to address the real world importance of these novel findings.

Just how much does ADHD actually affect children and young people? – Measuring health related quality of life in ADHD

Despite evidence to the contrary there are still those who question the importance of ADHD as a disorder and those who claim that these are just lazy and disruptive children. Recent studies have however demonstrated just how much ADHD interferes with the day to day lives of those who suffer from it. Together with colleagues across Europe we conducted a 2 year observational study of 1400 newly diagnosed children with ADHD (ADORE) focussing on both their quality of life and their ADHD symptoms. As a group their quality of life was severely impaired with scores on most measures being 2 standard deviations below the norms. However after systematically reviewing the literature on the measurement of quality of life in children with mental health problems it became clear that there are many measurement issues inherent to this type of work. We have therefore embarked on a series of studies, both independently and in collaboration with colleagues in the European Network for Hyperkinetic Disorders (EUNETHYDIS) to develop a clearer understanding of the relationships between quality of life as rated by different raters and instruments, between quality of life and clinical symptoms and impairment and ultimately to develop refined tools for measuring quality of life in children. We have also conducted health economic studies from which the measurement of QALYs for ADHD treatment used by NICE in their calculations were derived.

Translating research findings into clinical practice

Whilst it is of paramount importance that we generate a strong evidence base across all medical disciplines this evidence is of little practical value if it is not translated into clinical practice. Along with colleagues in the European Network for Hyperkinetic Disorders (EUNETHYDIS) we have developed several clinical guidelines for the assessment and management of ADHD and a programme to aid clinicians implement these guidelines into practice. We are also engaged in a 5 year project with colleagues in China (BANNANAS) assisting them to enhance clinical practice and to develop new models for ADHD care that facilitate accurate assessments to be conducted by non specialists. Much of this research would not be possible without the cooperation of the NHS Tayside Developmental Disorders Team whose flexibility and willingness to try out new ideas and models of service delivery have resulted the development of an internationally renowned clinical care pathway for ADHD and ensures the recruitment of well assessed children into our studies.

Current research includes

• The neuropsychology of ADHD and Conduct Disorder
• Neuropsychopharmacology of ADHD
• Pharmacogenomics of ADHD
• Clinical trials in ADHD and related disorders
• Molecular genetics and proteomics in ADHD (with Dr Kent @ St Andrews)
• Quality of life in ADHD and diabetes
• Development of service models for the assessment of ADHD in China (BANNANAS)

Coghill, D., Danckaerts, M., Sonuga-Barke, E., Sergeant, J., & the ADHD European Guidelines Group. (2009) Practitioner review: quality of life in child mental health - conceptual challenges and practical choices. Journal of Child Psychology & Psychiatry. vol. 50, no.5, p. 544 – 561

McCarthy, S., Asherson, P., Coghill, D., Hollis, C., Murray, M., Potts, L., Sayal, K., de Soysa, R., Taylor, E., Williams, T., & Wong, I. C. 2009, "Attention-deficit hyperactivity disorder: treatment discontinuation in adolescents and young adults", Br.J.Psychiatry, vol. 194, no. 3, pp. 273-277.

Coghill, D., Soutullo, C., d'Aubuisson, C., Preuss, U., Lindback, T., Silverberg, M., & Buitelaar, J. 2008, "Impact of attention-deficit/hyperactivity disorder on the patient and family: results from a European survey", Child Adolesc.Psychiatry Ment.Health, vol. 2, no. 1, p. 31.

Banaschewski, T., Coghill, D., Santosh, P., Zuddas, A., Asherson, P., Buitelaar, J., Danckaerts, M., Dopfner, M., Faraone, S., Rothenberger, A., Sergeant, J., Steinhausen, H.-C., Sonuga-Barke, E., & Taylor, E. 2008a, "Langwirksame Medikamente zur Behandlung der hyperkinetischen Störungen; Eine systematische Übersicht und europäische Behandlungsleitlinien Teil 1: Übersicht und Empfehlungen", Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie, vol. 36, no. 2, p. Mar.

Banaschewski, T., Coghill, D., Santosh, P., Zuddas, A., Asherson, P., Buitelaar, J., Danckaerts, M., Dopfner, M., Faraone, S., Rothenberger, A., Sergeant, J., Steinhausen, H.-C., Sonuga-Barke, E., & Taylor, E. 2008b, "Langwirksame Medikamente zur Behandlung der hyperkinetischen Störungen; Eine systematische Übersicht und europäische Behandlungsleitlinien Teil 2: Ein quantitativer Vergleich der langwirksamen Präparate", Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie, vol. 36, no. 2, p. Mar.

Matthews, K., Coghill, D., & Rhodes, S. 2008, "Neuropsychological functioning in depressed adolescent girls", J.Affect.Disord., vol. 111, no. 1, pp. 113-118.

Bangs, M. E., Hazell, P., Danckaerts, M., Hoare, P., Coghill, D. R., Wehmeier, P. M., Williams, D. W., Moore, R. J., & Levine, L. 2008, "Atomoxetine for the treatment of attention-deficit/hyperactivity disorder and oppositional defiant disorder", Pediatrics, vol. 121, no. 2, p. e314-e320.

Du, Y., Kou, J., & Coghill, D. 2008, "The validity, reliability and normative scores of the parent, teacher and self report versions of the Strengths and Difficulties Questionnaire in China", Child Adolesc.Psychiatry Ment.Health, vol. 2, no. 1, p. 8

Graham, J. & Coghill, D. 2008, "Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: epidemiology, prevention and management", Cns Drugs, vol. 22, no. 3, pp. 213-237.

Sonuga-Barke, E. J., Van Lier, P., Swanson, J. M., Coghill, D., Wigal, S., Vandenberghe, M., & Hatch, S. 2007, Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder : A growth mixture modelling analysis, Eur.Child Adolesc.Psychiatry. DOI, 10.1007/s00787-007-0667-3

Coghill, D. 2007, "Adding multimodal behavioural therapy to methylphenidate does not improve ADHD outcomes", Evid.Based Ment.Health, vol. 10, no. 4, p. 124.

*Coghill, D. R. , Rhodes, S. M, & Matthews, K., The neuropsychological effects of chronic methylphenidate on drug-naïve boys with Attention-Deficit/Hyperactivity Disorder (2007) Biological Psychiatry vol. 62, no. 9, pp. 954-962.

Sonuga-Barke, E. J., Coghill, D., Markowitz, J. S., Swanson, J. M., Vandenberghe, M., & Hatch, S. J. 2007, "Sex Differences in the Response of Children With ADHD to Once-Daily Formulations of Methylphenidate", J.Am.Acad.Child Adolesc.Psychiatry, vol. 46, no. 6, pp. 701-710.

Coghill, D., Spiel, G., Baldursson, G., Dopfner, M., Lorenzo, M. J., Ralston, S. J., & Rothenberger, A. 2006, "Which factors impact on clinician-rated impairment in children with ADHD?", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i30-i37.

Dopfner, M., Steinhausen, H. C., Coghill, D., Dalsgaard, S., Poole, L., Ralston, S. J., & Rothenberger, A. 2006, "Cross-cultural reliability and validity of ADHD assessed by the ADHD Rating Scale in a pan-European study", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i46-i55.

Preuss, U., Ralston, S. J., Baldursson, G., Falissard, B., Lorenzo, M. J., Rodrigues, P. R., Vlasveld, L., & Coghill, D. 2006, "Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i4-i14.

Riley, A. W., Coghill, D., Forrest, C. B., Lorenzo, M. J., Ralston, S. J., & Spiel, G. 2006a, "Validity of the health-related quality of life assessment in the ADORE study: Parent Report Form of the CHIP-Child Edition", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i63-i71.

Riley, A. W., Spiel, G., Coghill, D., Dopfner, M., Falissard, B., Lorenzo, M. J., Preuss, U., & Ralston, S. J. 2006b, "Factors related to Health-Related Quality of Life (HRQoL) among children with ADHD in Europe at entry into treatment", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i38-i45.

Rothenberger, A., Coghill, D., Dopfner, M., Falissard, B., & Steinhausen, H. C. 2006, "Naturalistic-observational studies in the framework of ADHD health care", Eur.Child Adolesc.Psychiatry, vol. 15 Suppl 1, p. i1-i3.

Wilson, H. K., Cox, D. J., Merkel, R. L., Moore, M., & Coghill, D. 2006, "Effect of extended release stimulant-based medications on neuropsychological functioning among adolescents with Attention-Deficit/Hyperactivity Disorder", Arch.Clin.Neuropsychol., vol. 21, no. 8, pp. 797-807.

Coghill D., Seth S. 2006 Osmotic, controlled-release methylphenidate for the treatment of ADHD. Expert Opin. Pharmacother. 7 (15) 2119 – 2138

*Rhodes, S. M., Coghill, D. R., & Matthews, K. Acute neuropsychological effects of methylphenidate in stimulant drug-naive boys with ADHD II – broader executive and non-executive domains. 2006 Journal of Child Psychology and Psychiatry 47:11 (2006), pp 1184–1194

Banaschewski, T., Coghill, D., Santosh, P., Zuddas, A., Asherson, P., Buitelaar, J., Danckaerts, M., Dopfner, M., Faraone, S. V., Rothenberger, A., Sergeant, J., Steinhausen, H. C., Sonuga-Barke, E. J., & Taylor, E. 2006, "Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline", Eur.Child Adolesc.Psychiatry, vol. 15, no. 8, pp. 476-495.

Coghill D. Making the most of scant resources: The development of an effective ADHD service ACAMH Occasional Papers No 24 (2006) 39 – 49

Remschmidt,H., Banaag, C., Bange,F., Bouvard,M. Castellanos,F.X., Coghill,D.R., Gomez-Plascencia,J., Greenhill,L., Huss,M.;, Rohde,L., Santosh,P., Schmidt,M., ShinY.-J., Taylor,E., Whiting,K. 2005, Global consensus on ADHD/HKD Eur.Child Adolesc.Psychiatry Vol. 14 Issue 3, pp127-137

Coghill D. (2005) Use of stimulants for attention deficit hyperactivity disorder, BMJ, 329, 907-908

Coghill D. (2005) Stimulant treatments for attention deficit/hyperactivity disorder - How safe are they really? Evidence.-based.Healthcare.& Public Health. 9, 83 - 85

*Rhodes, S. M., Coghill, D. R., & Matthews, K. Neuropsychological Performance in Drug Naïve Boys with ADHD, (2005) Psychological Medicine, 35, 1109–1120.

Banaag, C., Bange,F., Bouvard,M. Castellanos,F.X., Coghill,D.R., Gomez-Plascencia,J., Greenhill,L., Huss,M.; Remschmidt,H., Rohde,L., Santosh,P., Schmidt,M., ShinY.-J., Taylor,E., Whiting,K. (2005) Global Consensus on ADHD/HKD, European Child and Adolescent Psychiatry, 14, 127-137

Coghill, D. (2005) Delay of reinforcement gradients and Attention Deficit/Hyperactivity Disorder (ADHD): The challenges of moving from causal theories to causal models. Behavioural and Brain Sciences, 28, 428- 429

Coghill, D., Nigg, J. T., Rothenberger, A., Sonuga-Barke, E. J., & Tannock, R. (2005) Whither causal models in the neurobiology of ADHD. Developmental Science, 8, 105–114.

*Rhodes, S. M., Coghill, D. R., & Matthews, K. (2004), "Methylphenidate restores visual memory, but not working memory function in attention deficit-hyperkinetic disorder", Psychopharmacology (Berl), 175, 319-330

Taylor, E., Dopfner, M., Sergeant, J., Asherson, P., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Rothenberger, A., Sonuga-Barke, E., Steinhausen, H. C., & Zuddas, A. (2004), "European clinical guidelines for hyperkinetic disorder -- first upgrade", Eur.Child Adolesc.Psychiatry, vol. 13 Suppl 1, pp. I7-30.

Sonuga-Barke, E. J., Swanson, J. M., Coghill, D., DeCory, H. H., & Hatch, S. J. (2004) "Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: Preliminary indications from a secondary analysis of the COMACS study data", BMC.Psychiatry, vol. 4, no. 1, p. 28.