clozapine and Abnormalities--Multiple

Clozapine is licensed for the treatment of psychotic illnesses resistant to other antipsychotic medications. Velo-cardio-facial syndrome (VCFS) is associated with a vulnerability to psychotic illness that may be resistant to treatment with conventional typical and atypical antipsychotics.. A 32-year-old man with intellectual disability (ID) and a long history of treatment-resistant psychosis was found to have VCFS. Treatment with typical antipsychotic drugs and with one atypical olanzapine produced no improvement.. Treatment with clozapine produced an improvement in psychotic symptoms and associated behavioural abnormalities, but caused hypersalivation, constipation and a seizure disorder. The latter led to two fractures, one requiring surgery. The addition of sodium valproate stopped seizures.. Clozapine may improve psychotic symptoms for people with ID associated with VCFS, but clinicians should be alert for potential adverse effects.

Topics: Abnormalities, Multiple; Adult; Antipsychotic Agents; Cleft Palate; Clozapine; Face; Genetics, Behavioral; Heart Defects, Congenital; Humans; Intellectual Disability; Male; Psychotic Disorders; Syndrome

Human chromosome 22q11.2 has been implicated in various behavioral abnormalities, including schizophrenia and other neuropsychiatric/behavioral disorders. However, the specific genes within 22q11.2 that contribute to these disorders are still poorly understood. Here, we show that an approximately 200-kb segment of human 22q11.2 causes specific behavioral abnormalities in mice. Mice that overexpress an approximately 200-kb region of human 22q11.2, containing CDCrel, GP1Bbeta, TBX1, and WDR14, exhibited spontaneous sensitization of hyperactivity and a lack of habituation. These effects were ameliorated by antipsychotic drugs. The transgenic mice were also impaired in nesting behavior. Although Tbx1 has been shown to be responsible for many physical defects associated with 22q11.2 haploinsufficiency, Tbx1 heterozygous mice did not display these behavioral abnormalities. Our results show that the approximately 200-kb region of 22q11.2 contains a gene(s) responsible for behavioral abnormalities and suggest that distinct genetic components within 22q11.2 mediate physical and behavioral abnormalities.

Topics: Abnormalities, Multiple; Amphetamines; Animals; Antipsychotic Agents; Behavior, Animal; Chromosome Deletion; Chromosomes, Human, Pair 22; Clozapine; Disease Models, Animal; Female; Heterozygote; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Psychotic Disorders; Schizophrenia; Time Factors

A case of severe schizophrenia is described in a patient with chromosomal mosaicism of Klinefelter's syndrome (XXY) and trisomy 8. The literature of both syndromes is reviewed and the aetiological implications discussed.

Topics: Abnormalities, Multiple; Behavior Therapy; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 8; Clozapine; Combined Modality Therapy; Humans; Klinefelter Syndrome; Male; Middle Aged; Mosaicism; Schizophrenia, Paranoid; Trisomy