Plasma levels of S100B and neurofilament light chain protein in stress-related mental disorders.

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P < 0.001) and healthy controls (P < 0.001). Self-rated symptoms of cognitive failures were positively correlated with levels of S100B (rs = 0.434, P = 0.005) as were depressive symptoms (rs = 0.319, P < 0.001). Plasma levels of astrocyte-derived EVs were correlated with levels of S100B (rs = 0.464, P < 0.001). Plasma levels of NF-L did not differ between the groups and were not correlated with symptom severity or EV levels. Thus, long-term stress without sufficient recovery and SED may be associated with raised plasma levels of S100B, which may be evidence of pathophysiological changes in astrocytes. The findings also support the hypothesis that plasma levels of S100B are associated with cognitive dysfunction.

Impaired cognitive functioning in stress-induced exhaustion disorder: a new tablet-based assessment.

BACKGROUND: The adverse health effects of stress induced exhaustion disorder (SED) cause increasing concern in Western societies. This disorder is characterized by severe fatigue, decreased tolerance to further stress, and attention and memory lapses. Despite subjective complaints, individual cognitive deficits are not always detected in a clinical setting, which calls for the validation of more sensitive instruments. AIM: The objective of this study was to investigate if a short, tablet-based serial naming task, MapCog Spectra (MCS) could be used as a marker for cognitive problems in SED. PARTICIPANTS: The study comprised of 39 subjects (35 females, four males) with SED. Their mean age was 46,8 years (SD 10.1; range 30-60 yrs.). All participants were healthcare professionals, with a college or university degree, doctors, registered nurses, and psychologists. METHODS: The MCS was used to assess the number of aberrant pauses during serial naming of coloured geometrical shapes. The Coding, Matrix Reasoning, Digit Span, Symbol Search of the WAIS-IV, and RUFF 2&7 tests, were administered together with a short interview. RESULTS: Mean values were within normal reference limits for all tests, except for the MCS, which showed a significantly higher number of aberrant pauses (p < 0,001) in the SED group, compared to normal reference values. Although subjects performed within normal limits on the RUFF 2&7, a significant difference between individuals was found in the performance strategy of the participants. CONCLUSION: Here we report that subjects with SED have performance deficits on the MCS, in terms of aberrant pause times, despite average performance on WAIS-IV tests measuring inductive reasoning, processing speed, working memory, and attention. We also demonstrate that subjects use different strategies to overcome their problems. These findings add to the growing evidence of cognitive deficits in SED and that the MCS might aid neuropsychologists in disentangling cognitive markers, important to substantiate the subjective complaints of affected individuals.

Isoforms of soluble vascular endothelial growth factor in stress-related mental disorders: a cross-sectional study.

Vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood-brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF121, VEGF165, and VEGF121 + VEGF165 (VEGFtotal) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF121 and VEGF165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF121 (sVEGF121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGFtotal was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGFtotal and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.

Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study.

Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood-brain barrier.

Comparison of exhaustion symptoms in patients with stress-related and other psychiatric and somatic diagnoses.

BACKGROUND: Several rating scales assessing stress-related symptoms of exhaustion have emerged in recent years. However, more knowledge is needed about the performance of these rating scales in patients with stress-related disorders as well as in other patient groups. With the recently developed Karolinska Exhaustion Disorder Scale (KEDS), we compared symptoms of exhaustion in different patient groups that were sorted according to diagnosis. METHODS: Patients were sampled consecutively from departments of occupational medicine (DOM) at three Danish hospitals. The total study group comprised 698 care-seeking patients (487 women). Patients with stress-related diagnoses (n = 217; the International Classification of Diseases [ICD]-10 code F43: reaction to severe stress and adjustment disorder) were compared to a diverse group of patients with a range of somatic diagnoses (n = 338) and to patients with other psychiatric diagnoses (n = 143), including subgroups with major depression disorder (n = 34; F32 and F33) and problems related to employment and unemployment (n = 99; Z56). The data were analysed using linear mixed models with the SPSS statistical program. RESULTS: The mean KEDS sum score in patients with stress-related diagnoses (29.3; SD = 8.0) was significantly higher than in patients with other psychiatric diagnoses (25.9; SD = 9.5) and in patients with somatic diagnoses (17.6; SD = 10.8). The subgroup with a major depression disorder had high mean KEDS sum scores (31.4, SD = 8.1), similar to patients with stress-related diagnoses, while the mean KEDS sum score in patients with problems related to employment and unemployment (Z56) was 23.5 (SD = 9.0). Young and old patients scored similarly on KEDS, but in patients with somatic diagnoses, female patients scored significantly higher than male patients. CONCLUSION: The symptoms of exhaustion measured with KEDS were higher in patients with stress-related diagnoses and major depression disorder than in patients with somatic diagnoses. The intermediate level of the symptoms of exhaustion that were associated with problems related to employment and unemployment, (Z56) compared to the lower level of the symptoms with somatic diagnoses, suggests that KEDS might be useful in detecting mild, prodromal states of exhaustion. This needs further investigation.

Construction and evaluation of a self rating scale for stress-induced exhaustion disorder, the Karolinska Exhaustion Disorder Scale.

Prolonged stress (≥ six months) may cause a condition which has been named exhaustion disorder (ED) with ICD-10 code F43.8. ED is characterised by exhaustion, cognitive problems, poor sleep and reduced tolerance to further stress. ED can cause long term disability and depressive symptoms may develop. The aim was to construct and evaluate a self-rating scale, the Karolinska Exhaustion Disorder Scale (KEDS), for the assessment of ED symptoms. A second aim was to examine the relationship between self-rated symptoms of ED, depression, and anxiety using KEDS and the Hospital Anxiety and Depression Scale (HAD). Items were selected based on their correspondence to criteria for ED as formulated by the Swedish National Board of Health and Welfare (NBHW), with seven response alternatives in a Likert-format. Self-ratings performed by 317 clinically assessed participants were used to analyse the scale's psychometric properties. KEDS consists of nine items with a scale range of 0-54. Receiver operating characteristics analysis demonstrated that a cut-off score of 19 was accompanied by high sensitivity and specificity (each above 95%) in the discrimination between healthy subjects and patients with ED. Reliability was satisfactory and confirmatory factor analysis revealed that ED, depression and anxiety are best regarded as different phenomena. KEDS may be a useful tool in the assessment of symptoms of Exhaustion Disorder in clinical as well as research settings. There is evidence that the symptom clusters of ED, anxiety and depression, respectively, reflect three different underlying dimensions.