Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Abstract

To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

Neuroimmune Mechanisms and Sex/Gender-Dependent Effects in the Pathophysiology of Mental Disorders

“…Within weeks after administration of the cytokine IFN-a, patients experience symptoms (Capuron et al, 2002;Capuron and Miller, 2004) due to dopamine loss (Capuron et al, 2012). Similar results were reported in animal studies (Felger et al, 2007(Felger et al, , 2013 in which lipopolysaccharide or cytokine administration (IL-1b or IL-6) in mice resulted in loss of interest and reduction in reward sensitivity (Yohn et al, 2016;Bartlett et al, 2018). Another essential cofactor in monoamine synthesis, tetrahydrobiopterin, decreases in response to inflammation-induced oxidative stress (ROS and reactive nitrogen species), inducing anxiety and depressive symptoms (Neurauter et al, 2008;Haroon et al, 2012;Felger et al, 2013).…”

Widespread Morphometric Abnormalities in Major Depression

“…61 Moreover, an early increase in hippocampal volume and in rostral anterior cingulate thickness after 1 week of treatment was predictive of improved clinical response to antidepressant treatment with serotonin and noradrenaline reuptake inhibitor antidepressant drugs, suggesting that neuroplastic cellular changes may occur early and are predictive of subsequent clinical efficacy. 62,63 Furthermore, decreased hippocampal gray matter in MDD in a current depressive episode, relative to healthy participants and MDD in remission, subsequently showed increased gray matter after SSRI antidepressant treatment, 61 perhaps representing a human in vivo correlate of cellular neurogenesis with SSRI pharmacologic treatment in animal models. 64 MR imaging observable changes in hippocampal structure, as well as in other cortical and subcortical regions, reflect the complex inter-relationships of neurotoxic and neuroplastic cellular effects.…”

Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder

“…A multivariate pattern analysis using the gray matter and white matter magnetic resonance image at baseline differentiated treatment-sensitive patients from treatment-resistant patients with 82.9% accuracy [34]. A large, multisite, and placebo-controlled MRI study examined the association between the efficacy of sertraline and the cortical thickness at baseline and after 1 week [35]. It was found that increased cortical thickness of the rostral anterior cingulate cortex after 1 week of treatment was associated with better response to selective serotonin reuptake inhibitors (SSRI) at 8 weeks; however, the predictive accuracy (63.9%) in differentiating treatment response from nonresponse was relatively limited [35].…”

“…A large, multisite, and placebo-controlled MRI study examined the association between the efficacy of sertraline and the cortical thickness at baseline and after 1 week [35]. It was found that increased cortical thickness of the rostral anterior cingulate cortex after 1 week of treatment was associated with better response to selective serotonin reuptake inhibitors (SSRI) at 8 weeks; however, the predictive accuracy (63.9%) in differentiating treatment response from nonresponse was relatively limited [35]. The structural MRI results of 53 unipolar depressed patients showed that a larger amygdala volume was significantly associated with a lower post-electroconvulsive therapy (ECT) Montgomery-Asberg Depression Rating Scale score.…”