Prefrontal cortex resting state perfusion is determined by 5HTTLPR-polymorphism in patients with MDD

Abstract

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Objectives: Neuroimaging studies in major depressive disorder (MDD) have indicated dysregulation in a network involving prefrontal cortex, subgenual cingulate and amygdala. The serotonergic system is the principal target for pharmacologic treatment in MDD and the functional variable serotonin promotor polymorphism (5HTTLPR) influences susceptibility, course and treatment-response of MDD. In this study we examined resting state perfusion depending on 5HTTLPR-status in a large sample of MDD-patients.

Methods: 99mTc-HMPAO-SPECT was performed in 89 patients with MDD, stratified according to receptor polymorphism (group A: 41 patients with S/S and S/L genotype; group B: 34 patients with L/L genotype). Each patient received 2 SPECT-scans: initially (T1) and after 4 weeks of Citalopram treatment (T2). Two sample t-tests were performed in SPM 2 between the two subgroups at both time-points.

Results: There were no significant differences between both subgroups regarding age, gender, severity of depression, medication or treatment response (p<0.05). Group A, compared to group B, revealed a significantly higher resting state perfusion in the (mesial) prefrontal cortex (p<0.05, FWE-corrected). This effect was only significant at T1. Additional ROI analyses showed that the amygdala was also relatively overactive in group A.

Conclusions: Our data in patients with MDD demonstrate the influence of the 5HTTLPR gene polymorphism on resting state perfusion in key structures of the mood circuit. While the clinical significance of these imaging findings needs to be further investigated, the necessity to monitor 5HTTLPR-status is highly recommended in future MDD-imaging studies.