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

Abstract

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.

Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction

“…This finding indicates that the association between verbal memory and 5-HT 4 receptor in MDD was independent from the previously reported association between anxiety and 5-HT 4 receptor in this patient cohort. 38…”

“…Taking into account the educational level or the severity of depressive or anxiety symptoms did not substantially change the association between memory dysfunction and 5-HT 4 receptor. This finding indicates that the association between verbal memory and 5-HT 4 receptor in MDD was independent from the previously reported association between anxiety and 5-HT 4 receptor in this patient cohort …”

“…In this case-control study, we analyzed the primary outcome of the baseline program of the NeuroPharm trial; a detailed overview of the complete NeuroPharm trial is provided elsewhere . Additional analyses of the secondary and exploratory aims in the same cohort have been published, including data on functional MRI, electroencephalogram and event-related potential, cognition, oxidative stress, and anxiety symptoms …”

“…Reported P values for the secondary cognitive outcomes were corrected for 4 tests using the Bonferroni-Holm method to control for the familywise error rate (adjusted P value). To assess the potential role of educational, depression, and anxiety levels in the association between 5-HT 4 receptor BP ND and cognitive scores, we conducted post hoc analyses in which years of education, HAMD-17 scores, and 10-item Generalized Anxiety Disorder (GAD-10) scores, respectively, were included as covariates in the models.…”

“…27 Additional analyses of the secondary and exploratory aims in the same cohort have been published, including data on functional MRI, 31,32 electroencephalogram and event-related potential, 33,34 cognition, 35,36 oxidative stress, 37 and anxiety symptoms. 38…”