RT Journal Article SR Electronic T1 Relationship between sigma-1 receptor availability and depressive or cognitive symptoms in acute early onset unipolar depression: a (S)-(-)-[18F]Fluspidine PET investigation JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 106 OP 106 VO 62 IS supplement 1 A1 Philipp Meyer A1 Maria Strauss A1 Georg Becker A1 Swen Hesse A1 Klara Bednasch A1 Barbara Ettrich A1 Franziska Zientek A1 Michael Rullmann A1 Julia Luthardt A1 Steffen Fischer A1 Marianne Patt A1 Barthel Henryk A1 Bernhard Wunsch A1 Peter Brust A1 Osama Sabri YR 2021 UL http://jnm.snmjournals.org/content/62/supplement_1/106.abstract AB 106Objectives: The sigma-1 receptor (S1R) acts as a neuromodulator and may play an important role for cognitive and behavioral processes in neuropsychiatric disorders. Cognitive dysfunction is common in unipolar major depressive disorder (MDD). Using S1R-specific (S)-(-)-[18F]Fluspidine PET, the purpose of this study was to investigate the S1R availability and its relationship to depressive and cognitive symptoms in untreated patients with acute early onset MDD (EO-MDD). Methods: Acute, moderate to severe EO-MDD patients without antidepressive therapy (n = 13; age: 26 ± 6 years; 6 females; age at disease onset: 22 ± 5 years; Hamilton depression rating scale [HAMD-17] 19 ± 4) were investigated and compared with age- and sex-matched healthy controls (HC; n = 12; age: 25 ± 3 years; 6 females [n.s.]) using (S)-(-)-[18F]Fluspidine PET (300 MBq; 0-90 min p.i.; ECAT Exact HR+). Total distribution volumes (VT) were determined using kinetic modeling (2TCM, metabolite correction). Regional VOI-analyses were carried out. Cognitive state (memory, attention, executive function and working memory) was evaluated using the Wechsler memory scale (WMS) and the cognitive screening test PANDA. Results: In EO-MDD, compared with HC, WMS and PANDA scores were significantly lower indicating cognitive dysfunction (P < 0.05) and (S)-(-)-[18F]Fluspidine VT values were significantly higher especially within the nucleus caudatus, nucleus accumbens, orbitofronto-temporal, anterior cingulate and insular cortices, nucleus raphe and pons (P < 0.01). In EO-MDD, HAMD-17 correlated positively with VT, especially within the anterior and posterior cingulate and occipital cortices and midbrain (R ≥ 0.79; P < 0.01; nuisance WMS/PANDA), however, there were no significant correlations between VT and cognitive dysfunction (P < 0.05; nuisance HAMD-17). Conclusions: Using (S)-(-)-[18F]Fluspidine PET, we showed an increase of meso-striato-cortico-limbic and paralimbic S1R availability in untreated patients with acute, moderate to severe EO-MDD which was strongly correlated with the degree of depressive symptoms, but not with the cognitive state. These results provide motivation to apply S1R PET to a larger cohort of depressed patients at different disease stages, potentially also in follow-up after therapy initiation.