An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients

BACKGROUND: It was recently reported that an interaction of the dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the behavioural approach system – as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS) scales – in a sample of healthy German subjects. The Temperament and Character Inventory (TCI), in particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146). METHODS: Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI

A dopamine transporter polymorphism is a risk factor for borderline personality disorder in depressed patients

Background. Borderline personality disorder (BPD) is often co-morbid with major depression and may complicate its treatment. We were interested in differences in genetic and developmental risk factors between depressed patients with or without a co-morbid BPD. Method. Out-patients with major depressive disorder were recruited for two treatment trials. Assessment of depressed patients included the assessment of personality disorders, developmental risk factors and DNA samples for genetic analyses. Results. In each study there was a significant association between the 9-repeat allele of the dopamine transporter (DAT1) and BPD, with odds ratios (OR) >3 and p[less-than-or-eq, slant]0·02. This association remained significant when developmental risk factors for BPD (childhood abuse and neglect and borderline temperament) were also included in the analyses. The OR was even larger in the depressed patients aged [gt-or-equal, slanted]35 years (OR 9·31, p=0·005). Conclusion. This replicated association in depressed patients between the 9-repeat allele of DAT1 and BPD may provide clues to understanding the neurobiology of BPD. The finding that the association is larger in the older depressed patients, suggests that the 9-repeat allele may be associated with a poorer prognosis BPD, rather than a young adult limited variant of BPD