Attentional bias in individuals with depression and adverse childhood experiences: influence of the noradrenergic system?

Linn K Kuehl,Katja Wingenfeld,Christian E Deuter,Jan Nowacki,Christian Otte,Lisa Ueberrueck

doi:10.1007/s00213-021-05969-7

Abstract

RationaleMajor depressive disorder (MDD) is a severe mental disorder with affective, cognitive, and somatic symptoms. Mood congruent cognitive biases, including a negative attentional bias, are important for development, maintenance, and recurrence of depressive symptoms. MDD is associated with maladaptive changes in the biological stress systems such as dysregulations of central noradrenergic alpha2-receptors in the locus coeruleus-noradrenergic system, which can affect cognitive processes including attention. Patients with adverse childhood experiences (ACE), representing severe stress experiences in early life, might be particularly affected.ObjectivesWith an experimental design, we aimed to gain further knowledge about the role of noradrenergic activity for attentional bias in MDD patients with and without ACE.MethodsWe tested the effect of increased noradrenergic activity induced by the alpha2-receptor blocker yohimbine on attentional bias in a placebo-controlled repeated measures design. Four groups were included as follows: MDD patients with and without ACE, and healthy participants with and without ACE (total N = 128, all without antidepressant medication).ResultsA significant effect of MDD on attentional bias scores of sad face pictures (p = .037) indicated a facilitated attentional processing of sad face pictures in MDD patients (compared to non-MDD individuals). However, we found no such effect of ACE. For attentional bias of happy face pictures, we found no significant effects of MDD and ACE. Even though a higher increase of blood pressure and salivary alpha-amylase following yohimbine compared to placebo indicated successful noradrenergic stimulation, we found no significant effects of yohimbine on attentional bias of happy or sad face pictures.ConclusionsOur results are consistent with the hypothesis of a negative attentional bias in MDD patients. However, as we found no effect of ACE or yohimbine, further research is needed to understand the mechanisms by which ACE increases the risk of MDD and to understand the biological basis of the MDD-related negative attentional bias.

Highlights

Major depressive disorder (MDD) is a serious mental disorder associated with high subjective suffering and pronounced functional disruptions (Ferrari et al 2013; Otte et al 2016; Saarni et al 2007)
Since the noradrenergic system has an impact on cognitive processes (Chamberlain and Robbins 2013; Mather et al 2016; Sara 2016) and attentional biases (Ehlers and Todd 2017), dysregulations of the locus coeruleus-noradrenaline (LC-NA) system could play an important role in cognitive dysfunctions associated with MDD
We aimed to investigate whether alterations in the LC-NA system of MDD patients, e.g., in alpha-2 receptor functioning, may contribute to biased attention for emotional information

Summary

Introduction

Major depressive disorder (MDD) is a serious mental disorder associated with high subjective suffering and pronounced functional disruptions (Ferrari et al 2013; Otte et al 2016; Saarni et al 2007). Mood congruent cognitive biases in the processing of emotional information, such as an attentional bias for negative stimuli (Armstrong and Olatunji 2012; Caseras et al 2007; Mathews and MacLeod 2005; Peckham et al 2010), are a prominent feature of MDD and have been implicated in the development, maintenance, and treatment of MDD MDD associated alterations in the LC-NA system might contribute to negative biases in processing of emotional information in MDD patients. A single administration of the NA reuptake inhibitor reboxetine could reverse negative bias in emotional processing such as emotion recognition and memory of self-relevant information in MDD patients (Harmer et al 2009). A study from our group (Wingenfeld et al 2013) demonstrated a positive effect of a single administration of the alpha2-receptor blocker yohimbine on memory consolidation, which was more prominent in MDD patients compared to healthy controls. As the effect of NA stimulation on memory was significantly affected by self-reported childhood adversity in the group of MDD patients, alterations in the LC-NA system might be especially pronounced in a subgroup of MDD patients with a history of childhood adversity

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