Neuroticism Mediates the Association of the Serotonin Transporter Gene with Lifetime Major Depression
Munafo MR, Clark TG, Roberts KH and Johnstone EC;
Commented by , 17 Jan 2006
Background
An increasing number of studies suggest that neuroticism is a predictor of depression. If this is the case it may also explain the female preponderance of depression since neuroticism is more frequent among women.
The 5-HTTLPR serotonin transporter polymorphism has been associated with both neuroticism and depression. The 5-HTTLPR is a base pair insertion/deletion polymorphism in the 5’ regulatory region of the 5-HTT gene that results in a short and a long variant of the gene.
Nevertheless, few studies have investigated the interrelation between serotonin transporter polymorphism, neuroticism and depression.
Methods
A total of 752 patients from general practice in UK were invited to participate in the study including a blood test and two questionnaires: the Eysenck Personality Questionnaire (EPQ) and a questionnaire on depression assessing lifetime major depression according to DSM-IIIR criteria.
Results
Questionnaires and genotypes were available for 33% of the original 752 patients. No difference was found between participants and non-participants in age, sex distribution or allelic distribution.
A total of 54% reported lifetime major depression among patients with the s/s allel, 34% among the s/l allel and 34% among the l/l allel. Similarly, the neuroticism score on the EPQ was highest among the s/s group with no difference among the l/l group and the l/s group.
Additionally, those who reported a history of lifetime major depression had a higher neuroticism score. Finally, when the association between neuroticism and lifetime major depression was controlled for, the strength of the association between 5HTT-LPR genotype and lifetime major depression was significantly decreased.
Neuroticism accounted for 42% of the effect of the 5HTT-LPR genotype on lifetime major depression.
Professor Kessing's comments
These results suggest that neuroticism at least partly mediates the association between 5HTT-LPR genotype and lifetime major depression. It is still unclear whether neuroticism is a predictor of depression or a consequence of depression, i.e. a so-called "scar" effect following depression.
The present study cannot answer this due to its cross sectional design. Further, the study does not address the gender question related to depression or the influence of negative life events.
The clinical perspective of research like the present is that it would be possible to identify individuals who are at increased risk of developing depression and recurrence of depression on the background of genotyping and endophenotypes such as neuroticism.
It opens up for potential primary prophylaxis and better secondary prophylaxis. However, so far we need to understand the nature of depression in more detail.