Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

Marieke J Van Der Werf-Eldering,Huibert Burger,Rixt F Riemersma-Van Der Lek,Willem A Nolen,Esther A E Holthausen,André Aleman

doi:10.1371/journal.pone.0037119

Marieke J Van Der Werf-Eldering, Huibert Burger + Show 4 more

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https://doi.org/10.1371/journal.pone.0037119

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Abstract

BackgroundDysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.Methodology/Principal FindingsIn 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.Conclusions/SignificanceAs our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

Highlights

Bipolar disorder is characterized by recurrentmanic and depressive mood episodes
As we have found in a previous study that cognitive functioning was associated with depressive symptoms [26], we hypothesized that HPA axis activity might explain this association
In our previous study we showed that cognitive dysfunction is associated with depressive symptoms in bipolar disorder

Summary

Introduction

Bipolar disorder is characterized by recurrent (hypo)manic and depressive mood episodes. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been suggested to be involved [5,6,7]. For many years a change in set point of the HPA system, resulting in altered regulation of cortisol secretory activity [ expressed as hypercortisolism and impaired glucocorticoid receptor function; [8]] has been emphasized in (unipolar) depression [9,10,11] as well as bipolar disorder [12,13,14]. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning

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