BALTIMORE – Researchers identified markers in two genes involved in the production of norepinephrine that significantly linked with an increased rate of suicide attempts among patients with schizophrenia in an exploratory study of 241 patients.
If the findings are confirmed in expanded clinical studies, the results could advance physicians’ ability to identify patients with schizophrenia who have an elevated risk for attempting suicide, provide important leads for developing new agents to treat patients at risk for suicide, and help better target existing treatments to suicidal patients who could most benefit from them, Dr. Vincenzo De Luca said at the annual conference of the American Association of Suicidology.
Dr. Vincenzo De Luca
Elevated noradrenergic activity is associated with aggressive behavior, which led Dr. De Luca and his associates to explore the hypothesis that a link exists between genes involved in norepinephrine metabolism and suicidal behavior in patients with schizophrenia, explained Dr. De Luca, a psychiatrist at the University of Toronto. Prior work by his group led to preliminary evidence linking a marker in a gene involved in regulating the hypothalamic-pituitary-adrenal pathway to an increased risk for suicide attempts in patients with schizophrenia (J. Psychopharmacol. 2010;24:677-82).
The current study involved 241 patients who met the DSM-IV criteria for schizophrenia and were recruited from several psychiatric care facilities in the Toronto area. The patients averaged 36 years old, with an average duration of illness of 16 years; 71% were men; and 80% were white. Fifty-three of the patients (22%) had a history of at least one well-documented suicide attempt, a rate that fits with prior reports of suicide attempt rates of 20%-50% among patients with schizophrenia, he said.
A series of analyses showed no demographic or clinical differences between the suicide attempters and nonattempters. However, the genetic analysis showed two very statistically significant differences in the prevalence of specific genetic polymorphisms in two different genes involved in norepinephrine production. One marker was in the gene for tyrosine hydroxylase (the enzyme that converts tyrosine to dopamine), and the second marker was in the gene for dopamine beta-hydroxylase (the enzyme that converts dopamine to norepinephrine).
The tyrosine hydroxylase polymorphism linked with a 3.7-fold increased rate of suicide attempts, compared with patients without the marker. And the dopamine beta-hydroxylase polymorphism linked with a 3.5-fold increased rate of suicide attempts, compared with patients who lacked this marker.
If this finding is confirmed in a larger number of patients, it might mean that these markers could constitute "a predictive test to help clinicians assess a patient’s suicide risk," Dr. De Luca said in an interview. The findings may apply not only to patients with schizophrenia, but also to patients with bipolar disorder, a possibility that also needs assessment in future clinical studies, he said. Key elements in trying to make these genetic links are having "clean," well-characterized, and well-documented data about patients’ clinical status; their diagnosed phenotypes; their suicide-attempt histories; and their ethnicity, as well as a large number of potential genetic markers.
Dr. De Luca said he had no relevant financial disclosures.