Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response

Abstract

Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients (N = 153) from the CAN-BIND-1 cohort were treated for 8 weeks, and depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale at 0, 2, 4, 6, and 8 weeks. We identified three groups of patients according to response status: early responders (22.9%), later responders (32.0%), and nonresponders (45.1%). RNA sequencing was performed in blood obtained at weeks 0, 2, and 8. RNA expression was modeled using growth models, and differences in the longitudinal changes in expression according to response were investigated using multiple regression models. The expression of RNAs related to response was investigated in the brains of depressed individuals, as well as in neuronal cells in vitro. We identified four RNAs (CERCAM, DARS-AS1, FAM228B, HBEGF) whose change over time was independently associated with a response status. For all except HBEGF, responders showed higher expression over time, compared to nonresponders. While the change in all RNAs differentiated early responders from nonresponders, changes in DARS-AS1 and HBEGF also differentiated later responders from nonresponders. Additionally, HBEGF was downregulated in the brains of depressed individuals, and increased in response to escitalopram treatment in vitro. In conclusion, using longitudinal assessments of gene expression, we provide insights into biological processes involved in the intermediate stages of escitalopram response, highlighting several genes with potential utility as biomarkers of antidepressant response.

Correlations between patterns of activity and the response to treatment yield distinct signatures for different antidepressive treatments

“…For iCBT, the response appears linear (see [18]), and the response is most reliably evaluated at the end of the course (10 weeks). The response to SSRIs has been classified as either fast (stable response is reached within 2 weeks after treatment onset), or slow (response stabilizes after about 4-6 weeks) [42], while the drop in symptom severity can be documented within hours after a single dose of ketamine administration and is stable for a couple of days [5,43]. We assumed that symptom severity was stable before treatment and had reached a plateau after treatment at the time of recording.…”

SNORA69 is up-regulated in the lateral habenula of individuals with major depressive disorder

“…To test if antidepressant drugs have any effects on the expression of SNORA69 we utilized human NPC cultures were as described in Fiori et al 27 . Human neuronal cultures were screened for cytotoxic effects using the MTT assay, and antidepressants were applied at nontoxic concentrations as described by Lopez et al, 28 .…”

CompCorona: A Web Portal for Comparative Analysis of the Host Transcriptome of PBMC and Lung SARS-CoV-2, SARS-CoV, and MERS-CoV

“…The ubiquitous expression of the FAM228B gene, whose function has not yet been determined, in most tissues, including the brain, shows its functional importance. Changes in the expression of FAM228B are mentioned in depressed individuals who are treated with antidepressants and die from suicide (Fiori et al 2021). Also, overlapping relationships have been identified between the severity of inflammation, brain structure, and function during acute COVID-19, with the severity of depression and post-traumatic distress in survivors (Benedetti et al, 2021;Yang et al, 2021).…”