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

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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-HT4R) has been implicated in both depression and anxiety. This is the first study to investigate the association between the cerebral 5-HT4R 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-HT4R ligand [11C]-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-HT4R 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-HT4R 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-HT4R from serotonergic antidepressants. The 5-HT4R is a promising neuroreceptor for further understanding the underpinnings of concurrent anxiety in patients with depression.

TidsskriftTranslational Psychiatry
Udgave nummer1
Antal sider8
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Our gratitude goes to the participants and relatives who took part in the study, all investigators and collaborating recruiting sites within the Mental Health Services in the capital region of Denmark. We would like to recognize and thank the personnel involved in laboratory work and technical assistance, and especially; Lone Ibsgaard Freyr, Gerda Thomsen, Svitlana Olsen, Agnete Dyssegaard, Arafat Nasser, Bente Dall, Peter Steen Jensen, Dorthe Givard, Ida Marie Brandt and Anna Maria Florescu. Financial support was granted from various foundations: the Research Fund of the Mental Health Services—Capital Region of Denmark, the Innovation Fund Denmark and H. Lundbeck A/S (GrantID: 5189-00087 A), the Independent Research Fund Denmark (GrantID: DFF-6120-00038), the Lundbeck Foundation alliance BrainDrugs (GrantID: R279-2018-1145), the Research Council of Rigshospitalet, the Augustinus Foundation (GrantID: 16-0058), the G.J. Foundation and Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat. The fundings were given as unrestricted grants and did not involve decisions regarding the design of the study, data collection, analyses, interpretation, or writing.

Publisher Copyright:
© 2022, The Author(s).

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