Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study

• Published in: Translational psychiatry Vol. 12; no. 1; p. 273
• Main Authors: Köhler-Forsberg, Kristin, Ozenne, Brice, Larsen, Søren V., Poulsen, Asbjørn S., Landman, Elizabeth B., Dam, Vibeke H., Ip, Cheng-Teng, Jørgensen, Anders, Svarer, Claus, Knudsen, Gitte M., Frokjaer, Vibe G., Jørgensen, Martin B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.07.2022; Nature Publishing Group
• Subjects: 59/78; 631/378/340; 692/53/2423; Antidepressants; Anxiety; Behavioral Sciences; Biological Psychology; Medicine; Medicine & Public Health; Mental depression; Neurosciences; Pharmacotherapy; Psychiatry
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-022-02034-5

Concurrent anxiety is frequent in major depressive disorder and a shared pathophysiological mechanism between anxiety and other depressive symptoms is plausible. The serotonin 4 receptor (5-HT 4 R) has been implicated in both depression and anxiety. This is the first study to investigate the association between the cerebral 5-HT 4 R binding and anxiety in patients with depression before and after antidepressant treatment and the association to treatment response. Ninety-one drug-free patients with depression were positron emission tomography scanned with the 5-HT 4 R ligand [ 11 C]-SB207145. Depression severity and concurrent anxiety was measured at baseline and throughout 8 weeks of antidepressant treatment. Anxiety measures included four domains: anxiety/somatization factor score; Generalized Anxiety Disorder 10-items (GAD-10) score; anxiety/somatization factor score ≥7 (anxious depression) and syndromal anxious depression. Forty patients were rescanned at week 8. At baseline, we found a negative association between global 5-HT 4 R binding and both GAD-10 score ( p  < 0.01) and anxiety/somatization factor score ( p  = 0.06). Further, remitters had a higher baseline anxiety/somatization factor score compared with non-responders ( p  = 0.04). At rescan, patients with syndromal anxious depression had a greater change in binding relative to patients with non-syndromal depression ( p  = 0.04). Concurrent anxiety in patients with depression measured by GAD-10 score and anxiety/somatization factor score is negatively associated with cerebral 5-HT 4 R binding. A lower binding may represent a subtype with reduced natural resilience against anxiety in a depressed state, and concurrent anxiety may influence the effect on the 5-HT 4 R from serotonergic antidepressants. The 5-HT 4 R is a promising neuroreceptor for further understanding the underpinnings of concurrent anxiety in patients with depression.