Gene clue to male suicide risk

A gene mutation has been linked to a threefold increase in the risk of suicidal tendencies among men taking antidepressants, claim US scientists.

Changes to a gene encoding cyclic adenosine response element binding protein (CREB1) were associated with treatment-emergent suicidal tendency in men with depression.

CREB protein has previously been shown to be over expressed in the brains of people who have committed suicide, something that has been mirrored in animal models of depression.

Additionally, small changes - single nucleotide polymorphisms (SNPs) - in CREB1 have been linked to anger expression in men with depression, but not women.

The latest finding could lead to a pre-treatment genetic test for men with depression to identify which patients are at high risk of attempting suicide if prescribed antidepressants.

For the study, 1,447 men and women with non-psychotic major depressive disorder but no suicidal thoughts were prescribed a 12-week course of citalopram hydrobromide. Follow-up checks were carried out at two, four, six, nine and 12 weeks and suicidal tendency was assessed.

Among all the patients, 8.6 per cent reported suicidal thoughts or behaviours during at least one follow-up visit. Of the 539 men in the study, 10 per cent reported suicidal ideation.

Analysis of the CREB1 gene and nearby DNA areas was carried out in all participants.

Of five SNPs examined, the presence of two SNPs that flank CREB1 was significantly associated with treatment-emergent suicidal ideation in males.

In men with both of these high-risk alterations, a 16 per cent risk of suicidal thoughts was noted, compared with 5 per cent in men with none, said lead researcher Dr Roy Perlis, a psychiatrist at Massachusetts General Hospital.

'If we find the same thing in other studies, the goal would be to develop tests so we can predict who is more likely to have this side-effect,' he said.

'It's important to emphasise that the overall risk is still low and that more people are helped by antidepressants than experience this possible side-effect.

'I think it's likely that there are similar genes operating across gender lines, or perhaps in women alone.'

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