Relative Hypo- and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study

Maripuu, Martin; Wikgren, Mikael; Karling, Pontus; Adolfsson, Rolf; Norrbäck, Karl-Fredrik

doi:10.1371/journal.pone.0098682

Cited by 57 publications

(32 citation statements)

References 69 publications

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“…For example, hypercortisolism has long been implicated in depression and bipolar disorder (Carroll, 1982, Rush et al, 1996, Rybakowski and Twardowska, 1999, Maripuu et al, 2014), whereas hypocortisolism is more often associated with PTSD (Thaller et al, 1999, Yehuda et al, 2000, Kirschbaum et al, 2002, Rohleder et al, 2004). It has yet to be determined whether HPA dysregulation presents a risk factor for pathology or if it is part of the symptomatology of a given disorder.…”

Section: Discussionmentioning

confidence: 99%

Differential dendritic remodeling in prelimbic cortex of male and female rats during recovery from chronic stress

Moench

Wellman

2017

Neuroscience

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Chronic stress produces differential dendritic remodeling of pyramidal neurons in medial prefrontal cortex of male and female rats. In males, this dendritic remodeling is reversible. However, the timeline of recovery, as well as the potential for reversibility in females, is unknown. Here, we examined dendritic recovery of pyramidal neurons in layer II–II of prelimbic cortex in male and female rats following chronic restraint stress (3 h/day for 10 days). Dendritic morphology and spine density were analyzed immediately following the cessation of stress, or following a 7 or 10 day recovery period. Chronic stress produced apical dendritic retraction in males, which was coupled with a decrease in the density of stubby spine on apical dendrites. Further, following a 10-day recovery period, the morphology of neurons from stressed rats resembled that of unstressed rats. Male rats given a 7 day recovery period had apical dendritic outgrowth compared to unstressed rats. Immediately after cessation of stress, females showed only minimal dendritic remodeling. The morphology of neurons in stressed females resembled those of unstressed rats following only 7 days of recovery, at which time there was also a significant increase in stubby spine density. Males and females also showed different changes in baseline corticosterone concentrations during recovery. These findings not only indicate that dendritic remodeling in prelimbic cortex following chronic stress is different between males and females, but also suggest chronic stress induces differential hypothalamic-pituitary-adrenal axis dysregulation in males and females. These differences may have important implications for responses to subsequent stressors.

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Section: Discussionmentioning

confidence: 99%

Differential dendritic remodeling in prelimbic cortex of male and female rats during recovery from chronic stress

Moench

Wellman

2017

Neuroscience

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“…Additionally, the lack of full medical histories did not allow us to control for other psychiatric (i.e bipolar disorder) and medical (i.e. body mass index) co-morbidities that are known to influence HPA axis function and glucocorticoid sensitivity (Maripuu et al, 2014; Pasquali et al, 2002). Follow-up studies are necessary to replicate the current findings and expand the generalizability of the results to other populations of traumatized individuals as our urban study sample consisted primarily of African Americans of low socioeconomic status.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study

Michopoulos

Norrholm

Stevens

et al. 2017

Psychoneuroendocrinology

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Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD− (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD− control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p’s≤ 0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p<0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.

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“…Stress exposure during life may alter hypothalamic-pituitaryadrenal (HPA) axis responses when encountering novel stressful Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jad situations (Binder et al, 2008;Maripuu et al, 2014). Furthermore, stress exposure during childhood has long-term consequences on the ability to cope with stressors later in life (Horovitz et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

Kok

Sep

Veldhuijzen

et al. 2016

Journal of Affective Disorders

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a b s t r a c tBackground: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. Methods: Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/ or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. Results: PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. Limitations: The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. Conclusions: In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery.

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Relative Hypo- and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study

Cited by 57 publications

References 69 publications

Differential dendritic remodeling in prelimbic cortex of male and female rats during recovery from chronic stress

Differential dendritic remodeling in prelimbic cortex of male and female rats during recovery from chronic stress

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

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