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Genetics of Antipsychotic-induced Side Effects and Agranulocytosis

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Abstract

Antipsychotic medication has been enormously helpful in the treatment of psychotic symptoms during the past several decades. Unfortunately, several important side effects that can cause significant morbidity and mortality. The two most common are abnormal involuntary movements (tardive dyskinesia) and weight gain progressing through diabetes to metabolic syndrome. A more rare and life-threatening adverse effect is clozapine-induced agranulocytosis (CIA), which has been linked to clozapine use. Clozapine itself has a unique position among antipsychotic medications, representing the treatment of choice in refractory schizophrenia. Unfortunately, the potential risk of agranulocytosis, albeit small, prevents the widespread use of clozapine. Very few genetic determinants have been clearly associated with CIA due to small sample sizes and lack of replication in subsequent studies. The HLA system has been the main hypothesized region of interest in the study of CIA, and several gene variants in this region have been implicated, particularly variants of the HLA-DQB1 locus. A preliminary genome-wide association study has been conducted on a small sample for CIA, and a signal from the HLA region was noted. However, efforts to identify key gene mechanisms that will be useful in predicting antipsychotic side effects in the clinical setting have not been fully successful, and further studies with larger sample sizes are required.

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Dr. Gary Remington states that he has no conflict of interest. Dr. James Kennedy has received funding from Eli Lilly.

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  1. Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada

    Nabilah I. Chowdhury & James L. Kennedy

  2. Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St., Toronto, Ontario, M5T 1R8, Canada

    Gary Remington

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Chowdhury, N.I., Remington, G. & Kennedy, J.L. Genetics of Antipsychotic-induced Side Effects and Agranulocytosis. Curr Psychiatry Rep 13, 156–165 (2011). https://doi.org/10.1007/s11920-011-0185-3

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