Psychopharmacology (2005) 178: 286–295 DOI 10.1007/s00213-004-1993-5 ORIGINAL INVESTIGATION Danielle C. Turner . Andrew D. Blackwell . Jonathan H. Dowson . Andrew McLean . Barbara J. Sahakian Neurocognitive effects of methylphenidate in adult attention-deficit/hyperactivity disorder Received: 19 April 2004 / Accepted: 10 July 2004 / Published online: 27 August 2004 # Springer-Verlag 2004 Abstract Rationale: Features of childhood attention- deficit/hyperactivity disorder (ADHD) often persist into adulthood. It has been shown that adult ADHD is associated with various neurocognitive deficits, including impairments in spatial working memory (SWM) and attention. It is not known whether these deficits are ameliorated by methylphenidate in adult ADHD. Objectives: The aim of this study was to evaluate the neurocognitive effects of a single dose of methylphenidate on SWM, visual memory, spatial span and sustained attention in adult ADHD. Methods: Twenty-four adult patients, recruited from a specialised clinic for the assessment of adult ADHD, were entered into a double- blind, randomised, placebo-controlled crossover study using a single 30 mg dose of methylphenidate. Results: Eighteen patients met DSM-IV criteria for adult ADHD. Methylphenidate resulted in an improvement in SWM performance and sustained attention, together with a speeding in response time, in these patients. Six patients with attentional difficulties, who did not meet a DSM-IV diagnosis of ADHD, showed a different pattern of response to methylphenidate compared to the ADHD group. For the combined group, moderate correlations were shown between childhood ratings of ADHD (both self-reported and informant ratings) and response to methylphenidate on the SWM task. Conclusions: Adults with ADHD had a similar neurocognitive response to methylphenidate to that previously reported for childhood ADHD. Our results provide further support for the validity of the ADHD syndrome as defined by DSM-IV and indicate possible neurocognitive substrates for clinical improvement with chronic methylphenidate. Keywords Norepinephrine . Dopamine . Working memory . Attention . Impulsivity . Human . Attention- deficit/hyperactivity disorder . Cognitive enhancement . Spatial working memory Introduction Attention-deficit/hyperactivity disorder (ADHD) in chil- dren is characterised by symptoms of inattention, impulsivity and hyperactivity (American Psychiatric As- sociation 1994) and is associated with significant func- tional impairment (Faraone et al. 2000b). Increasingly it is being recognised that features of ADHD often persist into adulthood (Spencer et al. 1994; Barkley 1998; NIH 1998; Faraone et al. 2004), particularly the difficulties with attention and organisation of thought and actions (Galla- gher and Blader 2001). Impaired neurocognitive perfor- mance related to frontal lobe functions has also been described in this population (Seidman et al. 1998; Walker et al. 2000; Barkley et al. 2001; Dinn et al. 2001; Murphy 2002a; Ossmann and Mulligan 2003). For example, it has been shown that adult ADHD is associated with deficits in spatial working memory (SWM), planning, attention and response inhibition (Dinn et al. 2001; Gallagher and Blader 2001; Murphy 2002b; Nigg et al. 2002; Aron et al. 2003; Wodushek and Neumann 2003; McLean et al. 2004). Many of these neurocognitive deficits are reminis- cent of those seen in childhood ADHD (Solanto 1998; Logan et al. 2000), particularly the attentional and executive impairments (Barkley et al. 1992; Tannock et al. 1995; Pennington and Ozonoff 1996; Kempton et al. 1999; Barnett et al. 2001). Biological abnormalities have been associated with ADHD, including consistent demonstrations of abnormal cerebral catecholamine functioning (Castellanos and D. C. Turner . A. D. Blackwell . J. H. Dowson . B. J. Sahakian (*) Department of Psychiatry, School of Clinical Medicine, Addenbrooke’ s Hospital, University of Cambridge, Hills Road, Cambridge, CB2 2QQ, UK e-mail: dct23@cam.ac.uk Tel.: +44-1223-331209 Fax: +44-1223-336968 A. McLean Department of Psychological Medicine, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, UK