Increased sigma-1 receptor (S1R) availability and its association with depressive and cognitive symptoms in untreated patients with acute early onset unipolar depression (EO-UP): a (-)-F-18-Fluspidine PET study

Ziel/Aim The S1R acts as a neuromodulator and may play a pivotal role for cognitive and behavioral processes in neuropsychiatric disorders. Cognitive dysfunction is common in UP. Using S1R-specific (-)-F-18-Fluspidine PET, the aim of this study was to investigate the S1R availability and its relationship to depressive and cognitive symptoms in untreated patients with acute EO-UP.

Methodik/Methods Unmedicated patients with acute, moderate to severe EO-UP (n = 13; 26 ± 6ys; 6 females; age at disease onset 22 ± 5ys; Hamilton depression scale [HAMD] 19 ± 4) were investigated using (-)-F-18-Fluspidine PET (300 MBq, ECAT Exact HR+) and compared with age- and sex-matched healthy controls (HC; n = 12). Total distribution volumes (V_T) were determined using kinetic modeling (2TCM, metabolite correction) and regional VOI analyses. Cognitive state (memory, attention, executive function and working memory) was evaluated using the Wechsler memory scale (WMS) and the cognitive screening test PANDA.

Ergebnisse/Results In EO-UP (vs. HC), WMS and PANDA scores were sign. lower indicating cognitive dysunction (P < 0.05). Also, (-)-F-18-Fluspidine V_T values were sign. higher especially within the ncl. caudatus, ncl. accumbens, orbitofronto-temporal and anterior cingulate cortices, insula, ncl. raphe and pons (P < 0.01). In EO-UP, HAMD correlated positively with V_T, 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 sign. correlations btw. V_T and cognitive dysfunction (P < 0.05; nuisance HAMD).

Schlussfolgerungen/Conclusions Using (-)-F-18-Fluspidine PET, we showed higher meso-striato-cortico-limbic and paralimbic S1R binding in untreated patients with acute, moderate to severe EO-UP 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.

Publication History

Article published online:
08 April 2021