Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms.

22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS.

Asynchronicity of Organic and Psychiatric Symptoms in a Case of Sertraline Intoxication.

Sertraline is a selective serotonin reuptake inhibitor used as an antidepressant and antipanic agent in children and adolescents. Sertraline is well tolerated and its safety profile in overdose is favorable. However, sertraline overdose may cause a toxic hyperserotonergic state known as serotonin syndrome (SS). Serotonin syndrome may be misdiagnosed in children because it has been reported mostly in adults. In the present case report, we describe a 16-year-old female patient who ingested 2000 mg of sertraline to attempt suicide. The patient showed symptoms and signs suggestive of SS, characterized by an asynchronicity between organic and psychiatric symptoms. In addition, the patient showed a variability of psychiatric symptoms through time. Thirteen hours after sertraline overdose, she was poorly cooperative with poverty of speech and marked emotional tension, but she was oriented in space and time and was able to remember what happened to her and to reconstruct the dynamics of the fact. Twenty-four hours after sertraline overdose, the patient developed a delusion of reference associated with intense anxiety and depressed mood. In the present case report, we discuss the pathophysiologic mechanisms of the observed clinical manifestations and propose an observation period for sertraline overdose in children and adolescents that is sufficiently long (at least 72 hours) even in the absence of unstable vital signs.