Cholecystokinin-B receptor gene expression in cerebellum, pre-frontal cortex and cingulate gyrus and its association with suicide Tessi Sherrin a , Katrina Yi Ching Heng a , Yi Zhun Zhu a , Yoke Mei Tang b , Gilbert Lau b , Chay Hoon Tan a, * a Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore b Institute of Forensic Science and Medicine, Health Authority of Singapore, Outram Road, Singapore 169608, Singapore Received 8 August 2003; received in revised form 9 October 2003; accepted 26 November 2003 Abstract Suicide is a complex behaviour. Genetic and environmental factors are implicated in suicide. Both factors require genes to exert their effects. One gene hypothesized to be involved in the pathophysiology of suicide is cholecystokinin. Alterations in cholecystokinin receptor binding have been reported to be significant in young suicide victims as compared to matched controls in the frontal and cingulate cortex. In this study we report the Cholecystokinin-B gene expression using RT-PCR, between suicide completers [(N ¼ 10); mean age 37.2 ^ 12 years] and control subjects [(N ¼ 10); mean age 37.6 ^ 11.9 years]. Cholecystokinin-B gene expression was significantly higher in the cerebellum (P ¼ 0:006), cingulate gyrus (P ¼ 0:024) and pre-frontal cortex (P ¼ 0:017) of suicide completers when compared to their age and sex-matched controls. q 2003 Published by Elsevier Ireland Ltd. Keywords: Suicide; Cholecystokinin-B (CCKB); RT-PCR; Gene expression; Cerebellum; Pre-frontal cortex; Cingulate gyrus Suicide is a major public health concern in most industrialized countries worldwide. In recent years the suicide rate in Singapore has increased drastically. The underlying causes could be many. It is believed that over 90% of people who commit or attempt suicide have a diagnosable psychiatric disorder at the time of suicide, usually depression, alcohol abuse, schizophrenia or bipolar disorder [6]. Cholecystokinin (CCK) is one of the brain-gut peptides, first recognized as a gastrointestinal hormone mediating digestive function and gives ingestion produced satiety signals [10]. Receptors for CCK are divided into two groups: CCKA receptors which are abundant in the peripheral systems and some discrete brain regions and CCKB receptors which are widely present in the brain [2,8]. Neurotransmission in CCK has been implicated in the genesis of negative emotions, schizophrenia, anxiety and panic disorders [9]. The brain CCKB receptor has been implicated in mediating anxiety, panic attacks, satiety, and the perception of pain [4]. In a previous study, CCK and benzodiazepine receptor binding characteristics were analysed in the brain tissue samples from 13 suicide victims and 23 control cases [8]. There was significantly higher number of CCKB receptors and affinity constants in the frontal cortex of suicide victims. The results of investigation suggest that CCK-ergic neurotransmission is linked to self-destructive behaviour [8]. The investigation of CCK binding in the brains of suicide victims suggests an up-regulation of binding in the frontal and cingulate cortex in comparison to matched controls. However, significant differences in the CCKB receptor characteristics in the frontal cortex were observed only between younger suicides and controls [5]. Studies suggest that the cerebellum is essential to the neural circuitry subserving cognition and emotion. It connects with the reticular system (arousal), hypothalamus (autonomic function and emotional experience), limbic system (experience and expression of emotion), para limbic and neocortical association areas critical for higher order function (cognitive dimensions of affect) [7,13,14]. The cingulate gyrus is a major part of the ‘anatomical limbic system’ and is involved in emotion and mood [15]. The 0304-3940/03/$ - see front matter q 2003 Published by Elsevier Ireland Ltd. doi:10.1016/j.neulet.2003.11.072 Neuroscience Letters 357 (2004) 107–110 www.elsevier.com/locate/neulet * Corresponding author. Tel: þ 65-68743310; fax: þ 65-68737690. E-mail address: phctanch@nus.edu.sg (C.H. Tan).