A single dose of mirtazapine attenuates neural responses to self-referential processing

Abstract

Increased self-focus is a core factor in the psychopathology of depression. Cortical midline structures (CMS) are implicated in the neurobiology of self, depression and antidepressant treatment response. Mirtazapine, an antidepressant that increases serotonin and norepinephrine release, enhances processing of positive and attenuates processing of negative emotional information in healthy volunteers after a single dose. These early changes, which are opposite to the negative information bias in depression, may be important for the therapeutic effect of mirtazapine. It nevertheless remains unresolved whether/how mirtazapine specifically influences processing of self-referential emotional information.Half of the healthy volunteers (n=15/30) received a single dose of mirtazapine, in an open-label design, two hours before functional magnetic resonance imaging (fMRI), and the other half was scanned as a control group without medication. During fMRI the participants categorized positive and negative self-referential adjectives.Mirtazapine attenuated responses to self-referential processing in the medial prefrontal cortex and the anterior cingulate cortex. Mirtazapine further decreased responses to positive self-referential processing in the posterior cingulate cortex and parietal cortex.These decreased responses of the CMS suggest that mirtazapine may rapidly improve the ability of the CMS to down-regulate self-referential processing. In depressed patients, this could lead to decreased self-focus and rumination, contributing to the antidepressant effect.

Trait Sensitivity to Negative and Positive Feedback Does Not Interact With the Effects of Acute Antidepressant Treatment on Hedonic Status in Rats

“…In that latter study, acute agomelatine treatment reduced the sensitivity of rats to NF, as indexed by the decreased proportion of lose-shift behaviors, while mirtazapine increased the sensitivity of rats to PF, as indexed by the increased proportion of win-stay behaviors. This decrease in NF sensitivity and the increased sensitivity to PF were hypothesized to manifest antidepressantinduced, positive, information-processing biases, similar to those reported previously in humans following acute antidepressant treatment (Arnone et al, 2009;Rawlings et al, 2010;Komulainen et al, 2016).…”

Cognitive neuropsychological theory of antidepressant action: a modern-day approach to depression and its treatment

“…Most consistent and robust reports regarded the amygdala and the ACC, but changes in response to emotionally salient information were also observed across other relevant structures, such as medial prefrontal cortex (mPFC), insula, ventral striatum, thalamus, orbito-frontal cortex and dlPFC (e.g. Harmer et al 2004, Del-Ben et al 2005, Anderson et al 2007, Browning et al 2007, Miskowiak et al 2007, Bigos et al 2008, Harmer et al 2008, Murphy et al 2009a, Arnone et al 2009, Norbury et al 2009, Rawlings et al 2010, Maron et al 2016, Komulainen et al, 2016. A schematic representation of changes in brain activity over an acute (one dose) or shortterm (7-10 days) treatment with various antidepressant medications is shown in Fig.…”

Molecular imaging of the human emotion circuit

“…Some studies suggest that serotonergic system can influence how subjects interpret and process self-relevant affective information. Mirtazapine attenuates self-referential emotional processing in healthy volunteers, as manifested in decreased cortical midline activation (Komulainen et al, 2016) . This mechanism could underlie one serotonin-dependent antidepressant action, This is further evidenced in clinical trials, that show how short-term escitalopram treatment normalizes self-referential processing in patients with major depressive disorder (Komulainen et al, 2018).…”