TY - JOUR T1 - Increased sigma-1 receptor (Sig-1R) binding in the brain of unmedicated patients with acute major depressive disorder (MDD) using the novel Sig-1R-specific radioligand (-)-[<sup>18</sup>F]Fluspidine and PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 551 LP - 551 VL - 59 IS - supplement 1 AU - Philipp Meyer AU - Maria Strauss AU - Georg Becker AU - Swen Hesse AU - Klara Bednasch AU - Barbara Ettrich AU - Franziska Zientek AU - Michael Rullmann AU - Stephan Wilke AU - Julia Luthardt AU - Marianne Patt AU - Bernhard Wuensch AU - Peter Brust AU - Osama Sabri Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/551.abstract N2 - 551Objectives: The Sig-1R is a chaperone protein localized at the endoplasmatic reticulum (ER) that can translocate under ER stress, a mechanism which is critically involved in the pathophysiology of MDD. In order to investigate the pathophysiology of Sig-1R regulation in MDD, for the first time we quantitatively assessed Sig-1R binding in the brain of unmedicated, acute MDD and compared it with healthy controls (HC) using the novel radioligand (-)-[18F]Fluspidine and PET. Methods: Unmedicated patients with moderate to severe, acute MDD (n=12; 33±13ys; 6 males; HAMD: 19.0±4.3; MDD+ with family history [n=6] and MDD- without family history of depression [n=6]), were investigated using (-)-[18F]Fluspidine PET (~300 MBq, ECAT Exact HR+) and compared with age-/sex-matched healthy controls (HC; n=9; 37±16ys [n.s.]; 4 males [n.s.]). Distribution volume parameters (VT) were determined using full pharmacokinetic modelling (2TCM, metabolite correction). Regional VOI analyses were carried out. Results: Compared with HC, in MDD, VT was significantly higher within the ncl. Caudatus, ncl. Accumbens, fronto-temporo-parieto-occipital and cingulate cortices, insula, amygdala, thalamus and midbrain/raphe (+15 to +24%, P&lt;0.05). Compared with MDD-, in MDD+, VT was higher in the fronto-temporo and cingulate cortices, insula, hippocampus, putamen, thalamus (P&lt;0.05). There was an inverted-U relationship between the severity of MDD (HAMD) and VT in the fronto-temporo-parietal and posterior cingulate cortices and thalamus (P&lt;0.05). Conclusions: Using (-)-[18F]Fluspidine PET, we demonstrate for the first time higher Sig-1R binding in meso-striato-cortico-limbic and paralimbic brain regions of unmedicated patients with acute MDD. Higher Sig-1R binding in MDD+, compared with MDD-, may express different subtypes of depression. Increased Sig-1Rs in acute MDD and the inverted-U relationship between severity and Sig-1R may reflect neuroadaptive upregulation of Sig-1R counteracting ER stress that is exhausted in the severest stages of MDD leading to apoptosis. ER -