Elsevier

Psychoneuroendocrinology

Volume 36, Issue 2, February 2011, Pages 258-265
Psychoneuroendocrinology

Patterns of salivary cortisol secretion and responses to daily events in patients with remitted bipolar disorder

https://doi.org/10.1016/j.psyneuen.2010.07.016Get rights and content

Summary

Previous studies on bipolar disorder revealed abnormalities in the function of the HPA axis, including disturbed patterns of cortisol secretion, during depressive and manic episodes. It is less clear whether these abnormalities persist after symptomatic recovery. In the present study we used the experience sampling method with intensive salivary cortisol sampling to study patterns of cortisol secretion in relation to negative and positive daily events during the normal daily life of a group of 36 patients with remitted bipolar disorder and 38 healthy controls. Results of multilevel regression analysis indicated that daytime cortisol levels and reactivity to daily events were similar in remitted bipolar patients and healthy controls, but bipolar patients showed flatter diurnal slopes and larger cortisol fluctuations over successive measures. Patients with many previous episodes had higher overall cortisol levels, reduced cortisol reactivity to negative daily events, and flatter diurnal slopes than patients with fewer episodes. These results provide additional evidence of subtle HPA axis dysregulation in remitted bipolar patients, especially in those with many recurrent episodes.

Introduction

Many patients with bipolar disorders show evidence of increased activity at several levels of the hypothalamic–pituitary–adrenal (HPA) axis during depressive and manic episodes (Linkowski et al., 1994, Schmider et al., 1995, Cassidy et al., 1998, Rybakowski and Twardowska, 1999, Daban et al., 2005). Controversy exists whether these abnormalities are limited to the episodes themselves or might also be present before the onset of bipolar disorder or later, during periods of clinical remission. Offspring of parents with bipolar disorder have been reported to have elevated (Ellenbogen et al., 2006) or normal (Deshauer et al., 2006) basal cortisol levels; in general, studies of basal cortisol secretion in remitted bipolar patients provide little evidence of abnormalities (Cervantes et al., 2001, Watson et al., 2004, Thompson et al., 2005, Deshauer et al., 2006). However, evidence from challenge tests indicates persistent HPA dysfunction after clinical remission from bipolar episodes. For example, remitted bipolar patients have demonstrated intermittent cortisol non-suppression during monthly dexamethasone suppression tests (DSTs) (Deshauer et al., 1999). Moreover, a study using the combined dexamethasone/corticotropin releasing hormone (DEX/CRH) test reported an enhanced salivary cortisol response in symptomatic as well as in remitted bipolar patients, compared to healthy controls (Watson et al., 2004). These findings suggest that cortisol reactivity to psychosocial stressors might also be altered in remitted bipolar patients. Patients with unipolar depression tend to show decreased cortisol responses to laboratory as well as everyday psychosocial stressors (Peeters et al., 2003, Burke et al., 2005), whereas one study found that cyclothymic individuals showed heightened reactivity to a laboratory stressor (Depue et al., 1985). To our knowledge, cortisol reactivity to psychosocial stressors has not been studied in patients with bipolar disorder, either current or remitted. Furthermore, although basal cortisol secretion shows more random variability in individuals with cyclothymia (Depue et al., 1985) and in depressed patients under both naturalistic (Peeters et al., 2004) and controlled conditions (Posener et al., 2004), this indicator of dysregulated HPA activity has not previously been investigated in bipolar patients. In summary, although some studies suggest that HPA axis dysregulation precedes, accompanies and follows bipolar episodes and thus may be a trait characteristic (Daban et al., 2005), there is relatively little information on cortisol secretory patterns in remitted bipolar disorder. Better insight into these patterns may help elucidate whether HPA axis hyperactivity plays a role in the pathophysiology of bipolar disorders (Cousins and Young, 2005). Support for HPA involvement could in turn stimulate the development of therapeutic strategies that target this neuroendocrine system. The glucocorticoid receptor antagonist mifepristone, for example, has been shown to improve cognitive function and attenuate depressive symptoms in bipolar disorder (Young et al., 2004a).

The first aim of the present study was to provide a more complete description of cortisol secretory patterns during the normal daily life of patients with remitted bipolar disorder, in comparison to healthy controls. We therefore conducted an intensive sampling of salivary cortisol with simultaneous registration of daily hassles and uplifts. In the present study, participants collected saliva samples and completed self-report forms 10 times a day for 6 days, which allowed us to examine not only overall cortisol levels, but also the diurnal decline in cortisol levels, short-term reactivity of this hormone to daily stressors, and the degree of apparent random variability. We hypothesized that levels of cortisol secretion in remitted patients would be higher, more variable, and less responsive to daily events than in healthy controls. Our second aim was to investigate whether individual differences in cortisol secretion in the patient group could be explained by the number of previous episodes and the presence of subsyndromal symptoms.

Section snippets

Participants

Thirty-nine bipolar patients were recruited from lithium clinics in Maastricht and Sittard, The Netherlands. The main inclusion criterion was a primary diagnosis of Bipolar I or Bipolar II Disorder, without rapid cycling, as assessed with the Structured Clinical Interview for DSM-IV (First et al., 1996). Additional inclusion criteria were age between 18 and 65 years, in a state of partial or full remission (according to DSM-IV criteria) for more than 2 months, and under regular treatment

Descriptive characteristics

Of the 78 initial participants (39 patients and 39 controls), four (three patients and one control) were excluded from the analyses due to drop-out or inadequate volume of saliva. None of the participants was excluded from the study because of one of the other exclusion criteria. The final sample thus consisted of 36 patients (of whom 18 men) and 38 controls (of whom 15 men). Use of medication in the patient group was as follows: 15 patients received only lithium; the others used various

Discussion

The main findings of the present study point to subtle alterations in cortisol secretory patterns in remitted bipolar disorder: although daytime cortisol levels and reactivity to daily stressors appeared to be normal, patients showed flatter diurnal slopes and lower autocorrelation between successive cortisol measures than the healthy comparison group. In patients with many previous episodes, disturbances in cortisol secretory patterns appeared to be more widespread, with higher overall

Role of funding source

None.

Conflict of interest

There are no conflicts of interest.

Acknowledgements

We thank Dr. José Sulon, University of Liège, Belgium, for performing the cortisol assays, and Truda Driesen, Lilly Finders, and Frieda van Goethem for research assistance.

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