Neuroprogressive nature of sigma-1 receptor (Sig-1R) pathophysiology in unmedicated patients with acute major depressive disorder as investigated by (-)-F-18-Fluspidine PET

Ziel/Aim:

We have previously demonstrated that Sig-1R availability is increased in unmedicated acute MDD (MDD) using (-)-F-18-Fluspidine PET. In order to assess whether the Sig-1R pathophysiology in MDD is progressive, we investigated the relationship between Sig-1R and disease duration (DS), number of depressive episodes (DE) and Hamilton Score (HAMD) in this ongoing (-)-F-18-Fluspidine PET trial.

Methodik/Methods:

Moderate to severe MDD (n = 15; 31 ± 12ys; 8 males; DS 5 ± 9ys; DE 1.5 ± 0.8ys; HAMD: 20 ± 4) were studied using (-)-F-18-Fluspidine PET (300 MBq, ECAT Exact HR+) and compared with sex-/age-matched healthy controls (HC; n = 16; 33 ± 14ys [n.s.]; 7 males [n.s.]). Distribution volume parameters (V_T) were assessed by kinetic modeling (2TCM, metabolite correction). VOI-analyses were performed.

Ergebnisse/Results:

In MDD, vs. HC, V_T was sign. higher in fronto-temporal, cingulate and insular cortices, amygdala, striatum, thalamus and ncl. raphe (P < 0.05). There were sign. positive correlations between HAMD and V_T in cingulate and insular cortices, ncl. caudatus and thalamus (r = 0.48 to 0.75, P < 0.05, adjusted for DS, BMI) and sign. negative correlations between DS and V_T in orbitofrontal cortex and hypothalamus (r =-0.46 to -0.58, P < 0.05, adjusted for severity of MDD) and between DE and V_T in orbitofrontal cortex, hypothalamus, temporo-parietal and cingulate cortices, thalamus and cerebellum (r =-0.47 to -0.70, P < 0.05, adjusted for severity of MDD).

Schlussfolgerungen/Conclusions:

Using (-)-F-18-Fluspidine PET, we showed increased cortico-(para-)limbic Sig-1R availability in MDD, as compared with HC, that is associated with severity of acute depressive symptoms (HAMD). Remarkably, there is a negative relationship between DS and DE of MDD and Sig1-R availability, especially in orbitofrontal cortices and hypothalamus as well as in various (sub)cortical-(para)limbic and cerebellar brain regions. Although verification by longitudinal Sig1-R PET studies is needed, we demonstrated for the first time a neuroprogressive nature of Sig-1R pathophysiology in MDD.