By Anne M. Verhallen, Remco J. Renken, Jan-Bernard C. Marsman, and Gert J. ter Horst.

Experiencing stress can have a disadvantageous effect on mental well-being. Additional to the relation between suffering from chronic stress and depression, both stress (acute and chronic) and depression are associated with cognitive alterations, including working memory. The breakup of a relationship is considered to be a stressful event that can lead to symptoms of depression in otherwise healthy people. Additional to elevated depression scores, stress-related cognitive alterations may occur in this population as well. Therefore, in the present fMRI study we investigated whether experiencing a relationship breakup is associated with working memory alterations and whether this is related to depressive symptom severity. A three workload version of the n-back task (0-back, 1-back, 2-back) was used to measure working memory in subjects who experienced a breakup in the preceding 6 months (“heartbreak group”, n = 70) and subjects in a romantic relationship (“relationship group”, n = 46). Behavioral task performance was compared between the two groups. Functional MRI scans were analyzed using General Linear Model (GLM) activation analyses. Workload conditions were contrasted to each other and to baseline and group differences were assessed. To investigate whether brain networks are associated with depressive symptom severity within the heartbreak group specifically, a post hoc feature-based Independent Component Analysis was performed on the 2-back > 0-back contrast images to identify brain regions that covaried across subjects. Behaviorally, the heartbreak group performed similar at high workload (i.e., 2-back) and better at moderate workload (i.e., 1-back) than the relationship group. GLM analysis revealed an interaction between group and 2-back > 0-back, 2-back > 1-back and 2-back > baseline; the heartbreak group showed less precuneus activation compared to the relationship group. Furthermore, within the heartbreak group, we found a negative association between depressive symptom severity and a brain network representing mostly the precuneus, anterior cingulate gyrus and supplementary motor cortex. Our findings suggest that the effect of a breakup is accompanied by workload-dependent working memory alterations. Therefore, we propose that this population can potentially be used to investigate the interplay between stress, cognitive functioning and depression.

Introduction

Experiencing stress can have a disadvantageous effect on mental well-being. Stressful life-events are considered risk factors for developing symptoms of depression (Kendler et al., 1999). Furthermore, chronic stress and dysregulation of the stress response can lead to mood disorders, including depression (Bale, 2006). Additional to the relation between suffering from chronic stress and depression, both stress and depression are associated with cognitive alterations.

Acute stress as well as chronic stress is known to have an impairing effect on working memory functioning in healthy individuals. This effect can be present at either the behavioral level, neural level or both. For example, acute stress, induced by watching a movie with aversive violent content, led to decreased dorsolateral prefrontal cortex activation during performance of a working memory task in a healthy female sample, but not to aberrant behavioral performance (Qin et al., 2009). Another study, investigating the effect of executing a social stress test in male subjects, revealed that acute social stress reduced performance (slower reaction times and lower accuracy rates) at high workload (Schoofs et al., 2008). Furthermore, animal studies showed that chronic stress, induced by a model of restraint stress, resulted in a variety of neural, and associated cognitive capacity, alterations, including working memory impairment (Grizzell et al., 2014). These stress-induced cognitive impairments were found to be accompanied by structural changes in the prefrontal cortex (Cerqueira et al., 2007). In humans, suffering from chronic psychological stress was found to be associated with lowered cognitive abilities, including working memory (Mackenzie et al., 2009). Additionally, impaired cognitive performance on executive functioning related tasks was found in people suffering from severe work-related chronic stress (Ohman et al., 2007) and people who are on sick leave due to work stress showed lowered activation in prefrontal brain areas (at similar behavioral performance) during a working memory task (Sandström et al., 2012).

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