Correlation between serotonin (5-HTT) transporter availability and hormonal stress response depends on 5-HTTLPR genotype: A [11C]DASB PET study

Abstract

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Objectives: Research on biological conditions of depression and negative mood states has focused on serotonergic dysfunction, stress hormone dysregulation and genetic vulnerability, particularly SS homozygotes (5-HTTLPR). We investigated the interrelationship between these factors in patients with major depression (DEP), obsessive compulsive disease (OCD) and healthy controls (HC).

Methods: 19 drug-naive patients (10 DEP, 9 OCD) and 19 HC were investigated with [11C]DASB-PET. In all subjects, cortisol response after stimulation with dexamethason was measured and 5-HTTLPR genotype was assessed. 5-HTT binding potential (BP) was analyzed from a thalamus ROI as well as voxelwise.

Results: In multiple regression analysis, reduced BP in the thalamus was associated with increased cortisol response (P<.05), diagnosis of DEP or OCD (P<.001), female gender (P<.05) and age (P<.001; no other effects). In SS homocygotes, the correlation between BP and cortisol response was reversed (pos. correlation; interaction: P<.05). Voxelwise analysis confirmed that three effects were overlapping in the thalamus area: (1) group difference (patients < HC) (2) correlation between BP and cortisol response and (3) statistical interaction with 5-HTTLPR.

Conclusions: This is the first report about subjects with genetical vulnerability presenting an inversed correlation between hormonal stress response and 5-HTT availability in the thalamus. This finding may help to understand genetic vulnerability in major depression.