Binding potential changes of SERT in patients with depression are associated with remission: A prospective...

The status of remission in patients with major depressive disorder treated with selective serotonin reuptake inhibitors (SSRIs) is mostly evaluated with clinical rating scales. Morphological correlates of the remission status remain a rare event. Addressing this challenge, we investigated functional correlates of remission by assessment of serotonin and dopamine transporter availability (SERT and DAT) using single-photon emission computed tomography (SPECT). Our purpose was to identify changes in the SERT/DAT binding potential in accordance with the clinical improvement. Nineteen drug-naïve patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of major depression were included. [¹²³I]2β-carbomethoxy-3β-(4-iodophenyl)tropane(β-CIT) SPECT was obtained from each participant before (baseline) and after 6 weeks (follow-up) of standardized treatment with escitalopram. The [¹²³I]β-CIT-SPECT recordings were acquired 4 hr (SERT-weighted) and 20-24 hr p.i (DAT-weighted), and binding potentials (˜BP_ND: baseline, follow-up, and rate of change) were calculated for thalamus, midbrain, pons (SERT), and striatum (DAT). From all study participants, neuropsychiatric symptoms were assessed using Hamilton depression (HAM-D) and Beck Depression Inventory scores. At follow-up, patients were divided into responders and nonresponders (as well as remitters and nonremitters). Compared to nonremitted, remitted patients showed over the course of 6 weeks a significantly higher loss of SERT binding potential in the thalamus (p = .036) and in the midbrain (p = .019). Additionally, the correlation of HAM-D with SERT binding potential in the thalamus showed a trend toward significance (p = .057) with higher HAM-D scores (at baseline) leading to lower SERT binding potential. No significant associations were identified for the analysis of baseline prediction of therapy response with SERT and DAT. Our results suggest that patients who remit from their depressive symptoms under escitalopram are characterized by stronger decreases of SERT, indicating that escitalopram blocking of SERT leads to clinical improvement. Therefore, this study shows that measuring SERT availability with SPECT could be an efficient and applicable technique to illustrate a possible underlying pathophysiology of symptom remission in response to treatment. In addition, the present results could help to stimulate new treatment approaches based on SERT and DAT binding. (PsycInfo Database Record (c) 2023 APA, all rights reserved).