Keith Matthews

+44 (0)1382 383008
Head Of Neuroscience Division

Biography

Professor Matthews trained in medicine and psychiatry in Aberdeen and in behavioural neuroscience and experimental psychology in San Diego and Cambridge, respectively. He obtained his MBChB (1984) and MD (1997) degrees at the University of Aberdeen and his PhD (1998) from the University of Cambridge. His research interests include the influences of early experience on behavioural and neural development and the neurobiology and treatment of developmental psychiatric disorders, drug addiction, mood and anxiety disorders.

Research

Psychiatric disorders represent the great remaining “undiscovered country” of biomedical sciences. Despite the high prevalence rates of psychiatric disorders and the associated global health burden, research into aetiological mechanisms and the neurobiology underpinning treatment effects (and ‘treatment resistance’) remains in its infancy. There are many highly effective treatments for psychiatric disorders; indeed much of general psychiatric practice is supported by an extensive, high quality evidence base. For example, despite repeated and consistent media misrepresentation of the research evidence, antidepressant drug therapies are highly effective and safe treatments for most patients with Major Depression and Obsessive Compulsive Disorder. However, it is imperative that we develop novel and improved treatments, most notably for the many patients who do not experience satisfactory treatment responses to ‘first line’ therapies such as antidepressant medication and cognitive behavioural therapy. It order to achieve this goal, we must first improve our understanding of relevant aetiological factors and of underlying mechanisms of illness and mechanisms of action of existing effective therapies.

Professor Matthews’ main research interests fall within the domains of behavioural neuroscience, experimental psychology and clinical studies of the pathogenesis and treatment of Major Depression, Obsessive Compulsive Disorder (OCD), substance use disorders and addiction, and developmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD). Recent research projects have applied structural and functional neuroimaging approaches to the study of the pathophysiology of Major Depression (in collaboration with Professor Douglas Steele, Dr Reiner Sprengelmeyer -University of St Andrews, and Dr David Christmas), opiate addiction (in collaboration with Professor Douglas Steele and Dr Alex Baldacchino) and ADHD (in collaboration with Professor Douglas Steele and Dr David Coghill). Other active areas of research include:

  1. the efficacy and mechanisms of ventral striatum and subthalamic nucleus deep brain stimulation for refractory OCD (MRC-funded study with Professor Eileen Joyce, Institute of Neurology, London as Principal Investigator).
  2. the use of health informatics to evaluate treatment outcomes for treatment seeking substance misuse populations (with Dr Brian Kidd and Dr Alex Baldacchino)
  3. the use of neuropsychological testing to refine the behavioural phenotyping of developmental psychiatric disorders – ADHD and Conduct Disorder (with Dr David Coghill, Dr Sarah Seth and Dr Helen Smith).
  4. the evaluation of psychological therapies for chronic Major Depression (with John Swan, Bob MacVicar and Dr David Christmas)

Neurosurgery for Mental Disorder

Targeted lesions in brain structures are used to treat to a small number of individuals each year with severe, chronic, and treatment-refractory depressive illness and obsessive-compulsive disorder. Dundee hosts the only UK centre performing such procedures within a national specialist service funded by the National Service Division of NHS Scotland (http://www.advancedinterventions.org.uk). There has been a neurosurgical treatment programme for psychiatric disorders in Dundee since 1992. This was established by George Fenton (my predecessor as Professor of Psychiatry) and local neurosurgeon T.K. Varma. International studies confirm that a significant proportion of patients accrue long-term benefits from surgery, with surprisingly modest rates of adverse effects (Shields et al., Biol Psychiatry 2008, 64, 449-454), including a key study from Dundee (Steele et al., Biol Psychiatry 2008, 63, 670-677). The mechanism(s) of action remain unknown, although we have recently reported a striking relationship between lesion placement and clinical outcome (as above), confirming that the structural and functional impact of such lesions is critically dependent upon which groups of neurons and/or fibres of connection are affected.

With the context of delivering a national specialist service for NHS Scotland, the Advanced Interventions Service is committed to the rigorous evaluation of a range of treatment approaches for patients with chronic, refractory mood disorders and OCD. These approaches include psychological therapies (e.g. CBASP, ERP and CBT), neurostimulation (vagus nerve stimulation – VNS and deep brain stimulation – DBS) and lesion surgery (anterior capsulotomy and anterior cingulotomy).

Professor Matthews is executive adviser to the World Society for Stereotactic & Functional Neurosurgery Psychiatric Neurosurgery Committee.

Professor Matthews is Clinical Lead for Tayside and a member of the Management Board of the Scottish Mental Health Research Network (http://www.smhrn.org.uk/).

Professor Matthews is a Member of the Clinical Advisory Group for the charity OCD action

PhD supervision

ongoing, Cassie Higgins Chronic Pain and Opioid Dependence, PhD (p/t), 1st

ongoing, Tracy Stewart (University of Strathclyde) Depression and suicidal ideation in adolescents, PhD, 2nd

2014, Helen Smith The neuropsychological functioning of boys with Conduct Disorder, MD, 1st

2013, Brian Kidd Long Term Outcomes of Methadone Substitution Therapy (OST-M) for Opiate Dependency: The Effect of Patient Characteristics and Co-Morbidities, MD, 1st

2012, Benson Mwangi Predictive Modelling of Neuroimaging data in Major Depressive Disorder, PhD, 2nd

2012, Alex Baldacchino Neuropsychological function as a result of chronic exposure to methadone and other opioids, PhD, 1st

2009, David Coghill Heterogeneity in Hyperkinetic Disorder, MD, 1st

2008, Gominda Ponnamperuma Development, implementation and evaluation of a medical school selection test: the objective structured selection examination (OSSE), PhD, 2nd

2006, David Christmas Functional Neurosurgery for Intractable Mental Disorder: Long Term Effects on Mental Health, Neuropsychological Performance, Social Function, and Quality of Life, MD, 1st

2004, Eleanor Sorrell The management of depression: treatment outcomes and the prediction of response., PhD, 1st

2002, Sinead Rhodes The neuropsychopharmacology of ADHD, PhD, 1st

Group members

  • Mrs. Christine Matthews
  • Ms. Cassandra Higgins

Teaching

Teaching commitments include lectures and tutorials within the Phase II undergraduate medical curriculum during the block teaching on Psychiatry.

Publications

McMurdo, M.E.T., Witham, M.D., Johnston, D., Struthers, A.D., Guthrie, B., Matthews, K. (2014) Identifying older heart failure patients with major depression in primary care; a feasibility study. International Journal of Geriatric Psychiatry Vol 29 Issue 5, 547-9 doi: 10.1002/gps.4089

Powell, T.R. McGuffin, P., D’Souza, U.M., Cohen-Woods, S., Hosang, G.M., Martin, C., Matthews, K., Day, R.K., Farmer, A.E., Tansey, K.E., Schalkwyk, L.C. (2014) PLoS One Mar 11:9(3):e91076. Doi:10.1371/journal.pone.0091076

Nuttin, B., Wu, H., Mayberg, H., Hariz, M., Gabriëls, L., Galert, T., Merkel, R., Kubu, C., Vilela-Filho, O., Matthews, K., Taira, T., Lozano, A., Schechtmann, G., Doshi, P., Broggi, G., Régis, J., Alkhani, A., Sun, B., Eljamel, M., Schulder, M., Kaplitt, M., Eskandar, E., Rezai, A., Krauss, J., Hilven, P., Schuurman, R., Ruiz, P., Chang, J.W., Cosyns, P., Lipsman, N., Voges, J., Cosgrove, R., Li, Y & Schlaepfer, T. (2014) Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders. Journal of Neurology, Neurosurgery and Psychiatry Jan 20 doi: 10.1136/jnnp-2013-306580

Swan, J. S., Macvicar, R., Christmas, D., Durham, R., Rauchhaus, P., McCullough, J. P. & Matthews, K. (2014) Cognitive Behavioural Analysis System of Psychotherapy (CBASP) for chronic depression: Clinical characteristics and six month clinical outcomes in an open case series. Journal of Affective Disorders Vol 152, 268-276 doi: 10.1016/j.jad.2013.05.080

Gradin, V. B., Baldacchino, A., Balfour, D., Matthews, K., Steele, J. D. (2014) Abnormal Brain Activity During a Reward and Loss Task in Opiate Dependent Patients Receiving Methadone Maintenance Therapy. Neuropsychopharmacology vOL 39 iSSUE 4, 885-894. doi: 10.1083/NPP.2013.289

Coghill, D. R., Seth, S., Matthews, K. A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway model. Psychological Medicine Oct 31:1-13

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Cross-Disorder Group of the Psychiatric Genomics Consortium. Nature Genetics. (2013) 45: 484-494.

Christmas, D., Tolomeo, S., Steele, J.D., Eljamel, M.S. & Matthews, K. Vagus nerve stimulation for chronic major depressive disorder: 12-month outcomes in highly treatment-refractory patients. Journal of Affective Disorders. (in press) http://dx.doi.org/10.1016/j.jad.2013.05.080

Coghill, D.R., Hayward, D., Grimmer, C., Rhodes, S., Matthews, K. (2013) A longitudinal examination of neuropsychological and clinical functioning in boys with ADHD: Improvements in executive functioning do not explain clinical improvement. Psychological Medicine Jul 19:1-13 doi:10.1017/S0033291713001761

Hazari, H., Christmas, D. & Matthews, K. (2013) The clinical utility of different quantitative methods for measuring treatment resistance in major depression. Journal of Affective Disorders Vol 150 Issue 2 231-236 doi: 10.1016/j/jad. 2013.03.030 http://dx.doi.org/10.1016/j.jad.2013.03.030

Johnston, BA., Mwangi, B., Matthews, K., Coghill, D., Steele, JD. (20130 Predictive Classification of Individual Magnetic Resonance Imaging Scans from Children and Adolescents. Eur Child Adol Psychiatry dEC, 22(12)733-44 doi: 10.1007/s00787-012-0319-0

Gradin, V., Waiter, G., Kumar, P., Stickle, C., Milders, M., Matthews, K., Reid, I., Hall, J., Steele, J.D. (2012) Abnormal Neural Responses to Social Exclusion in Schizophrenia. PLoS ONE 7(8): e42608.

Gradin V., Waiter G., O'Connor A., Romaniuk L., Stickle C., Matthews K., Hall J., Steele J.D. Salience network-midbrain dysconnectivity and blunted signals in schizophrenia. Psychiatry Research: Neuroimaging. (2013) 211; 104-111

Baldacchino A, Balfour DJ, Passetti F, Humphris G & Matthews K. Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis. Neurosci Biobehav Rev. (2012); 36(9): 2056-2068.

Mwangi, B., Ebmeier, K., Matthews, K. & Steele, J.D. Multicentre Diagnostic Classification of Individual Structural Neuroimaging Scans from Patients with Major Depressive Disorder. Brain (2012); 35(1): 64-71

Mwangi, B., Matthews, K. & Steele, J.D. Prediction of Illness Severity in Patients With Major Depression Using Structural MR Brain Scans. Journal of Magnetic Resonance Imaging (2012); 35: 64–71

Stone J, Carson A, Duncan R, Roberts R, Coleman R, Warlow C, Murray G, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Sharpe M. Which neurological diseases are most likely to be associated with ‘‘symptoms unexplained by organic disease’’? J. Neurol. (2012); 259: 33-38.

Christmas D, Eljamel MS, Butler S, Hazari H, MacVicar R, Steele JD, Livingstone A & Matthews K. Long term outcome of thermal anterior capsulotomy for chronic, treatment refractory depression. Journal of Neurology, Neurosurgery and Psychiatry 2011; 82(6):594-600

Sklar P, Ripke S, Scott JL, Andreassen AO, Cichon S, Craddock N, Edenberg JH, Nurnberger IJ, Rietschel M, Blackwood D, Matthews K, Day, R, et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genetics (2011); 43: 977-83.

Sprengelmeyer, R, Steele, J.D., Mwangi, B., Kumar, P, Christmas, D., Milders, M. & Matthews. K. The insular cortex and the neuroanatomy of major depression. Journal of Affective Disorders 2011; 133: 120–127

Tozzi F, Manchia M, Galwey N, Severino G, Del Zompo M, Day R, Matthews K, Strauss J, Kennedy J, McGuffin P, Vincent J, Farmer A & Muglia P. Admixture analysis of age at onset in bipolar disorder. Psychiatry Research 2011; 185: 27-32.

Bajbouj M, Merkl A, Schlaepfer T, Frick C, Zobel A, Maier W, Corcoran C, Adolfsson A, Trimble M, Rau H, Hoff H-J, Padberg F, Müller-Siecheneder F, Audenaert F, van den Abbeele D, Matthews K, Christmas D, Eljamel M & Heuser I. Two-year Outcome of Vagus Nerve Stimulation (VNS) in Treatment-resistant Depression. 2010; 30 (3): 273-281.

Rhodes S, Riby D, Matthews K & Coghill D. ADHD and Williams syndrome: shared behavioural and neuropsychological profiles. Journal of Clinical and Experimental Neuropsychology 2010; 33(1): 147-156.

Liu JZ, Tozzi F, Waterworth D, et al. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics 2010; 42: 436–440.

Stone J, Carson A, Duncan R, Coleman R, Roberts R, Warlow C, Hibberd C, Murray G, Cull R, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Smyth R, Walker J, MacMahon AD & Sharpe M. Who is referred to neurology clinics? The diagnoses made in 3781 new patients. Clinical Neurology and Neurosurgery 2010; 112: 747-751.

Sharpe M, Stone J, Hibberd C, Warlow C, Duncan R, Coleman R, Roberts R, Cull R, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Smyth R, Walker A, Walker J, MacMahon A, Murray G & Carson A. Neurology out-patients with symptoms unexplained by disease: illness beliefs and financial benefits predict 1-year outcome. Psychological Medicine 2010; 40: 689-698.

Scott LJ, Muglia P, Kong XQ, Guan W, Flickinger M, Upmanyu R, Tozzi F, Li JZ, Burmeisterg M, Absher D, Thompson RC, Francks C, Meng F, Antoniades A, Southwick AM, Schatzberg AF, Bunney WE, Barchask JD, Jones EG, Day R, Matthews K, McGuffin P, Strauss JS, Kennedy JL, Middleton L, Roses AD, Watson SJ, Vincent JB, Myers RM, Farmer AE, Akil H, Burns DK & Boehnke M. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. PNAS 2009; 106 (18): 7501-7506.

Wilkie MJV, Smith G, Day RK, Matthews K, Smith D, Blackwood D, Reid IC & Wolf CR. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics Journal 2009; 9(1): 61-70.

Stone J, Carson A, Duncan R, Coleman R, Roberts R, Warlow C, Hibberd C, Murray G, Cull R, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Smyth R, Walker J, MacMahon AD & Sharpe M. Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up? Brain 2009; 132: 2878-2888.

Ridout, N., Dritschel, B., Matthews, K., McVicar, M., Reid, I. & O’Carroll, R. Memory for emotional faces in major depression following judgement of physical facial characteristics at encoding. Cognition and Emotion 2009; 23: 739-752.

Cruikshank G, MacGillivray S, Bruce D, Mather A, Matthews K, Williams B. Cross-sectional survey of patients in receipt of long-term repeat prescriptions for antidepressant drugs in primary care. Mental Health in Family Medicine 2008; 5: 105–9.

Matthews K, Coghill D. & Rhodes S. Neuropsychological functioning in depressed adolescent girls. Journal of Affective Disorders 2008; 111: 113-118.

Schlaepfer, T., Frick, C., Zobel, A. et al., Vagus Nerve Stimulation for depression: Efficacy and Safety in a European Study. Psychological Medicine 2008; 38: 651-661.

Steele, J.D., Christmas, D., Eljamel, M.S., Matthews, K. Anterior Cingulotomy for major depression: Clinical outcome and relationship to lesion characteristics. Biological Psychiatry 2008; 63: 670-677.