Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression

Gold, Stefan M.; Krüger, Schulamith; Ziegler, Kristin; Krieger, Thorsten; Schulz, Karl‐Heinz; Otte, Christian; Heesen, Christoph

doi:10.1136/jnnp.2010.230029

Cited by 89 publications

(107 citation statements)

References 47 publications

(43 reference statements)

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“…The role of cortisol as a potential mediator of any association between psychological stress and fatigue in MS provides a potential avenue for future research incorporating ambulatory assessment. Although Salivary cortisol studies appear to suggest attenuated daily cortisol variability in chronic fatigue syndrome (Powell, Liossi, Moss-Morris, & Schlotz, 2013), no association was found between salivary cortisol output and fatigue in MS in a previous study (Gold et al, 2011).…”

Section: Combining Subjective and Physiological Assessmentsmentioning

confidence: 88%

Ambulatory Assessment in Neuropsychology

Schlotz

Powell

2014

Zeitschrift für Neuropsychologie

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Zusammenfassung AbstractNeuropsychological disorders involve a variety of symptoms that often lead to substantial functional impairments in daily life. Research, assessment, and treatment should include a reference to daily life, considering symptoms, personality, and life circumstances of the individual patient. Ambulatory assessment methodology provides progress by avoiding retrospective memory-based bias, increasing ecological validity, and by generating individual time series that permit idiographic analysis. Using multiple sclerosis as an example, we illustrate new findings generated by ambulatory assessment studies in the areas of fatigue, stress and cognitive functions, and we demonstrate future opportunities presented by ambulatory assessment methodology to research and clinical practice with multiple sclerosis patients.

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Section: Combining Subjective and Physiological Assessmentsmentioning

confidence: 88%

Ambulatory Assessment in Neuropsychology

Schlotz

Powell

2014

Zeitschrift für Neuropsychologie

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“…Importantly, changes in 11b-HSD2 activity may play a role in autoimmunity: 11b-HSD2 is expressed in active MS lesions (Heidbrink et al, 2010) and increased 11b-HSD2 activity has been found in other inflammatory conditions such as rheumatoid arthritis (RA) (Schmidt et al, 2005), potentially contributing to limited anti-inflammatory effects of endogenous glucocorticoids in these diseases. In addition, we have previously reported a higher frequency of TNFa-producing CD8+ Tcells upon ex vivo stimulation in depressed MS patients compared to matched patients without comorbid depression (Gold et al, 2011). While it is unclear if this results in higher levels of this cytokine in the circulation or the CNS, TNFa can induce NFkB and thereby cause inactivation of GR (Pace and Miller, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Indirect evidence from our previous studies in MS-depression also points towards MR-dysfunction: We have recently shown that circadian cortisol profiles in depressed MS patients are characterized by elevated nadir levels but normal morning levels compared to non-depressed MS patients as well as healthy controls (Gold et al, 2010(Gold et al, , 2011. In humans, the circadian trough of cortisol secretion is largely mediated via the high-affinity mineralocorticoid receptor (MR), while circadian peak levels in the morning are more strongly depen-dent on low-affinity glucocorticoid receptors (GR) (Kellner and Wiedemann, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Female relapsing-remitting multiple sclerosis (RRMS) patients without depression (n = 12) and female depressive RRMS patients (n = 12) were recruited from the MS outpatient clinic in the University Hospital Hamburg Eppendorf, as described (Gold et al, 2011). They were matched according to Expanded Disability Status Scale Score (EDSS) (Kurtzke, 1983) and age.…”

Section: Subjectsmentioning

confidence: 99%

“…Ysrraelit et al, 2008) are also observed in MS. Furthermore, there is evidence that during the early stages of the disease, neuroendocrine-limbic abnormalities may be specific for MS patients who exhibit depressive symptoms (Fassbender et al, 1998;Gold et al, 2010Gold et al, , 2011Kern et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression

Fischer

Otte

Krieger

et al. 2012

Psychoneuroendocrinology

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Summary Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for 'escape' of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, we here investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. We performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of T cell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To our knowledge, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

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Diagnostic accuracy for major depression in multiple sclerosis using self‐report questionnaires

Fischer

Nicholls

et al. 2015

Brain and Behavior

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ObjectiveMultiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires are largely lacking. This could be particularly relevant for high-risk patients with depressive symptoms. Here, we compare the diagnostic accuracy of the Beck Depression Inventory (BDI) and 30-item version of the Inventory of Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder (MSS) against diagnosis by a structured clinical interview.MethodsPatients reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent diagnostic assessment (Mini International Neuropsychiatric Interview, M.I.N.I.). Receiver-Operating Characteristic analyses were performed, providing error estimates and false-positive/negative rates of suggested thresholds.ResultsData from n = 31 MS patients were available. BDI and IDS-SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total score, cognitive subscore, and BDI showed excellent to good accuracy (area under the curve (AUC) 0.86, 0.91, and 0.85, respectively).ConclusionBoth the IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as a screening tool and to quantify affective/cognitive depressive symptomatology.

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Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression

Cited by 89 publications

References 47 publications

Ambulatory Assessment in Neuropsychology

Ambulatory Assessment in Neuropsychology

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression

Diagnostic accuracy for major depression in multiple sclerosis using self‐report questionnaires

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