Genetics - Tardive Dyskinesia Risk Factors
The movement disorder known as tardive dyskinesia is due to side effects caused by a class of drugs used to treat the mentally ill (primarily those who suffer from schizophrenia). These drugs are called anti-psychotics or neuroleptics, and were first developed in Europe in the late 1940s and early 1950s from a compound that doctors had studies as a non-narcotic sedative. The first such drug, known as chloropromazine or CPZ, was first introduced to in the U.S. in 1954, marketed by Smith Kline & French (now GlaxoSmithKline) under the brand name Thorazine®.
Side effects of Thorazine® and similar drugs soon became apparent; CPZ was eventually phased out and a new generation of medications were developed. However, these were not necessarily an improvement. The main benefit was that this second generation of drugs delayed the onset of the symptoms of tardive dyskinesia; these symptoms nonetheless continued to appear among patients so treated.
It has now been shown that "second generation," or "atypical" medications for schizophrenia represent only a minimal improvement over their "first generation" predecessors, also known as "typical" medications. Incredibly, "typical" prescriptions are still widely prescribed in much of the world.
Risk Factors
Although the side effects of neuroleptic medications are real and serious, they affect no more than 30 percent of the patients who take them. Therefore, a substantial amount of what little research has been done on tardive dyskinesia has focused on what makes some patients more susceptible to the side effects of antipsychotic medications.
Factors that may cause a predisposition to tardive dyskinesia include age, gender (women are more at risk), a history of smoking and/or substance abuse, and genetics. When it comes to genetic factors, what makes a patient vulnerable to tardive dyskinesia may be due to ancestry and family history, a genetic mutation, or both.
Ethnicity
Statistics indicate that people of African ancestry are more susceptible to developing tardive dyskinesia. What is not clear is why this susceptibility exists.
It has been noted that the majority of patients prescribed neuroleptic medications who are not of European ancestry are in fact African or African-American. Americans of African descent run twice the risk of developing tardive dyskinesia as other groups, but the reason for this may be economic rather than genetic; psychiatrist Dr. William Glazer has noted that African-Americans from low-income areas are "disproportionately prescribed typicals," or first-generation neuroleptics. Dr. Glazer also expresses concern that the U.S. privatized health care system in which profitability takes priority over what is best for the patient may lead to increasing use of typical medications.
Mutations
Other studies carried out in India suggest that some type of genetic mutation affecting the metabolism may in fact constitute a risk for developing tardive dyskinesia. One such gene that has been implicated is identified as CYP2D6, which is involved in the metabolism of what are known as "xenobiotics," which can include certain drugs or bodily chemicals that are somehow produced in excess amounts. Another gene that may play a part in this disorder is called CYP1A2, which appears to have a "significant association with schizophrenia." Significantly, this particular study found that patients who carried this gene and used tobacco were more likely to develop tardive dyskinesia symptoms.
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