J Neural Transm (2007) 114: 939–945 DOI 10.1007/s00702-007-0631-x Printed in The Netherlands Comparison of cognitive functions between people with silent and wild-type butyrylcholinesterase I. Manoharan 1 , A. Kuznetsova 2 , J. D. Fisk 3 , R. Boopathy 1 , O. Lockridge 4 , S. Darvesh 5 1 Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, India 2 Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada 3 Departments of Psychology, Psychiatry and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada 4 Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA 5 Departments of Medicine, Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada Received: October 12, 2006 = Accepted: January 11, 2007 = Published online: February 22, 2007 # Springer-Verlag 2007 Summary In the human brain, butyrylcholinesterase (BuChE) is expressed in neurons and glia. For example, many nuclei in the human thalamus, with projections to the cerebral cortex, contain a large number of neurons with intense BuChE activity. Thalamocortical projections subserve a variety of cognitive functions. Due to genetic mutations, there are individuals who do not have detectable BuChE activity (silent BuChE). While the prevalence of silent BuChE is only 1:100,000 in European and American populations, it is 1:24 in the Vysya community in Coimbatore, India. To examine whether there are differences in cognitive functions between individuals with silent BuChE and those expressing normal BuChE (wild-type), twelve healthy individuals with silent BuChE and thirteen healthy individuals with wild- type BuChE, all from the Vysya community in Coimbatore, were tested for cognitive function using the Automated Neuropsychological Assessment Metrics test battery. The silent BuChE group was slightly faster on simple reaction tasks, but slower on a visual perceptual matching task. Furthermore, discriminant function analyses correctly classified 11=12 silent and 8=13 wild-type BuChE subjects (76% correct classification overall) based on BuChE status. Different profiles of cognitive test performance between indi- viduals with silent and wild-type BuChE were observed. These observations suggest a function for BuChE in cognition. Keywords: Butyrylcholinesterase genetic polymorphism, thalamus, cerebral cortex Introduction Human butyrylcholinesterase (BuChE; EC 3.1.1.8) is a gly- coprotein enzyme belonging to the family of serine esterases. It is found in various compartments in the body including the plasma and the brain. Although its biological function has yet to be clearly defined, it catalyses the hydrolysis of endogenous esters of choline such as acetylcholine, propion- ylcholine and butyrylcholine (Silver, 1974), as well as the growth hormone secretagogue, octanoyl ghrelin (De Vriese et al., 2004). In the plasma, BuChE deactivates several classes of compounds that are potentially harmful to the nor- mal physiological functions. These toxic compounds include naturally occurring ingested esters and carbamates, as well as glycoalkaloids found in solanacea plants such as pota- toes, tomatoes and eggplants (McGehee et al., 2000). It also detoxifies highly poisonous synthetic compounds such as the organophosphates (Silver, 1974; Taylor and Radic, 1994). Furthermore, BuChE is involved in the metabolism of various drugs including the deactivation of succinylcho- line and the conversion of prodrugs such as bambuterol into active drugs (Tunek et al., 1988). In the brain, the function of BuChE remains an enigma. Histochemical examination of the distribution of BuChE in the mammalian brain shows that it is expressed in the endothelium of the cerebral blood vessels, glia and neurons (Okinaka et al., 1961; Friede, 1967; Tago et al., 1992; Darvesh et al., 1998; Darvesh and Hopkins, 2003). In the human brain, BuChE is expressed in high numbers of neurons in areas that subserve a variety of cognitive func- tions (Darvesh et al., 1998; Darvesh and Hopkins, 2003). Expression of BuChE in a distinct and precise manner within brain structures suggests that this enzyme may have important roles in the function of the brain. For example, in the human thalamus, many nuclei that project to the ce- rebral cortex (Steriade et al., 1997), contain a large number Correspondence: S. Darvesh, Room 1308, Camp Hill Veterans’ Memorial, 5955 Veterans’ Memorial Lane, Halifax, Nova Scotia, B3H 2E1, Canada e-mail: sultan.darvesh@dal.ca