Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study

Abstract

Background: The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy.

Methods: 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later.

Results: Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio.

Conclusion: Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

Keywords: antidepressants; depression; magnetic resonance spectroscopy; maintenance therapy; recurrence.

Figure 1

Study schematic.

Figure 2

MRS measurements of NAA/Cr. (____) Followed-up until recurrence of depressive episode. (-----) Followed-up until start of antidepressant medication withdrawal. Horizontal axis: 1 – Start of the recovery phase; 2 – Start of the recovery phase + 6 months. Error bars denote 95%CI of means. *p < 0.005 t-test.

Figure 3

MRS measurements of Cho/Cr. (____) Followed-up until recurrence of depressive episode. (-----) Followed-up until start of antidepressant medication withdrawal. Horizontal axis: 1 – Start of the recovery phase; 2 – Start of the recovery phase + 6 months. Error bars denote 95%CI of means. **p < 0.001 t-test.

Figure 4

MRS measurements of Glx/Cr. (____) Followed-up until recurrence of depressive episode. (-----) Followed-up until start of antidepressant medication withdrawal. Horizontal axis: 1 – Start of the recovery phase; 2 – Start of the recovery phase + 6 months. Error bars denote 95%CI of means.