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

¹ Nuclear Medicine, PET and Radiopharmacy; ² Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany; ³ Psychiatry and Psychotherapy, Charité (CCM), Berlin, Germany

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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.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Reimold, M. Articles by Heinz, A. PubMed Articles by Reimold, M. Articles by Heinz, A.