Tic-related cognition, sensory phenomena, and anxiety in children and adolescents with Tourette syndrome.

BACKGROUND: Tourette syndrome is a protoypical example of developmental psychopathology, with the varying expressions of the disorder and its consequences appearing over time. Sensory urges typically appear after age 10 and are often followed by anxiety and depression. OBJECTIVE: To study the associations among tic-related cognitions, premonitory urges, and tic severity in children with Tourette syndrome at different stages of the illness. SUBJECTS: Fifty-seven consecutive patients referred to a tic disorders clinic. INSTRUMENTS: A battery of instruments was completed: Yale Global Tic Severity Scale, Premonitory Urge for Tics Scale, Screen for Child Anxiety Related Emotional Disorders, and Child Depression Inventory. To examine cognitions, a new measure was developed: the Beliefs About Tics Scale. RESULTS: Strong correlations were found between tic-related beliefs and both premonitory urges and tic-related impairments (as measured by the Yale Global Scale). Tic-related beliefs were also strongly correlated with depression in children older than 13 years but not in younger children. CONCLUSIONS: The significant correlations between tic-related cognitions, premonitory urges, and tic-related impairments in children emphasize the important role of psychological and sensory factors in the understanding of Tourette syndrome and in its treatment.

Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys.

Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced 2 hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hours following Albu-CocH administration. In behavioral experiments in monkeys, pre-treatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 µg/kg/injection) for over 24 hours. Pre-treatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative-stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted.

Tic disorders and the premonitory urge.

The aims of this study were to examine a non-English (Hebrew) version of a scale that measures the premonitory urge in children suffering from tic disorder, as well as examine the correlations of the urge with demographic and clinical aspects of Tourette Syndrome. Forty children and adolescents, suffering from tics participated in this study. They were assessed with the Premonitory Urge for Tics Scale (PUTS); the Yale Global Tic Severity Scale (YGTSS); the Childhood Version of the Yale Brown Obsessive Compulsive Scale (CYBOCS); the ADHD Rating Scale IV (Conners) Scale; the Screen for Child Anxiety Related Emotional Disorders (SCARED); and the Child Depression Inventory (CDI). The mean PUTS score was 20.15 (SD = 5.89). For the entire sample the PUTS was found to be internally consistent at a = 0.79. Youths older than 10 years had higher consistency (a = 0.83) than youths younger than 10 (a = 0.69). Premonitory urge was not correlated with tic severity in the entire sample. In youths older than 10, as opposed to youths younger than 10, premonitory urge did correlate with obsessions, compulsions and depression, but not with anxiety or with ADHD. The premonitory urge can be measured reliably and the PUTS is a useful instrument for measuring this important phenomena. Premonitory urges seems to be related to obsessions, compulsions, and depression in older children and this may have implications for the developmental psychopatholgy of these symptoms.