Burnout - das Zusammenspiel von Stress-Symptomen und Stress-Biomarkern

Einleitung Stressbedingte Erkrankungen, wie z.B. Burnout oder mittelgradige depressive Episode, sind geprägt von Symptomen der Erschöpfung, Depression, Angst sowie somatischen Beschwerden. Stressverarbeitungsstörungen zeigen sich zudem durch Veränderungen in unterschiedlichen physiologischen Parametern. Dazu gehören biologische Marker des vegetativen Nervensystems (z.B. Herzratenvariabilität (HRV)) und der neuronalen Plastizität (z.B. brain-derived neurotrophic factor (BDNF)). In dieser Studie ging es darum, zu zeigen, wie eine Verbesserung der subjektiven Stresssymptome nach erfolgreicher Therapie mit einem spezialisierten Behandlungskonzept mit Veränderungen in biologischen Markern von Stress assoziiert ist. Methode Es wurden 74 Patienten mit einer psychiatrischen Diagnose (F32.x (N=42), F33.x (N=29), F4 (N=3)) im Rahmen einer Stressverarbeitungsstörung (Burnout) eingeschlossen, die in stationärer Behandlung mit einem multimodalen Therapieansatz waren. Bei Ein- und Austritt (Dauer des Aufenthalts: 6-8 Wochen) wurden ihnen Fragebögen, z.B. zu Burnout- und Depressionssymptomen, abgegeben sowie die HRV im Schlaf und der BDNF-Spiegel im Blut gemessen. Ergebnisse / Schlussfolgerung Nach dem stationären Aufenthalt zeigte sich bei den Patienten eine signifikante Reduktion der Burnout- und Depressionssymptomatik sowie eine Verbesserung der Schlafqualität. Diese subjektive Verbesserung der Stresssymptome korrelierte deutlich mit einer Erhöhung des BDNF-Spiegels. Die HRV, bzw. die Parasympathikusaktivität im Schlaf zeigte keine signifikante Veränderung. Die Wirkung einer erfolgreichen Therapie scheint sich somit relativ schnell auf der Ebene der neuronalen Plastizität zu zeigen. Es wurde mehrfach belegt, dass eine moderate sportliche Betätigung sich besonders günstig auf den BDNF-Spiegel auswirkt. Das spricht somit für die Wirksamkeit des angewendeten, auf stressbedingte Erkrankungen spezialisierten Therapiekonzepts, das mehrere körperlich aktivierende Elemente integriert, welche die BDNF-Spiegelerhöhung mitunterstützt haben könnten. Dass am Ende des stationären Aufenthaltes bei den Patienten keine Veränderung in der Schlaf-HRV gezeigt werden konnte, weist darauf hin, dass neurovegetative Anpassungen längere Perioden der Erholung und des Stressmanagements beanspruchen könnten

No Evidence for XMRV in German CFS and MS Patients with Fatigue Despite the Ability of the Virus to Infect Human Blood Cells In Vitro

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV), a novel human retrovirus originally identified in prostate cancer tissues, has recently been associated with chronic fatigue syndrome (CFS), a disabling disease of unknown etiology affecting millions of people worldwide. However, several subsequent studies failed to detect the virus in patients suffering from these illnesses or in healthy subjects. Here we report the results of efforts to detect antibody responses and viral sequences in samples from a cohort of German CFS and relapsing remitting multiple sclerosis (MS) patients with fatigue symptoms. METHODOLOGY: Blood samples were taken from a cohort of 39 patients fulfilling the Fukuda/CDC criteria (CFS), from 112 patients with an established MS diagnosis and from 40 healthy donors. Fatigue severity in MS patients was assessed using the Fatigue Severity Scale (FSS). Validated Gag- and Env-ELISA assays were used to screen sera for XMRV antibodies. PHA-activated PBMC were cultured for seven days in the presence of IL-2 and DNA isolated from these cultures as well as from co-cultures of PBMC and highly permissive LNCaP cells was analyzed by nested PCR for the presence of the XMRV gag gene. In addition, PBMC cultures were exposed to 22Rv1-derived XMRV to assess infectivity and virus production. CONCLUSION: None of the screened sera from CFS and MS patients or healthy blood donors tested positive for XMRV specific antibodies and all PBMC (and PBMC plus LNCaP) cultures remained negative for XMRV sequences by nested PCR. These results argue against an association between XMRV infection and CFS and MS in Germany. However, we could confirm that PBMC cultures from healthy donors and from CFS patients can be experimentally infected by XMRV, resulting in the release of low levels of transmittable virus

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

A biological perspective on differences and similarities between burnout and depression

To compare and contrast burnout and depression is not only a conceptual issue, but may deliver important directions for treatment approaches and stabilize the awareness of disease which is essential for affected individuals. Because of the symptomatic overlap, it is a subject of multidimensional research and discussion to find specific signatures to differentiate between the two phenomena or to present evidence that they are different aspects of the same disorder. Both pathologies are regarded as stress-related disorders. Therefore, in this review burnout and depression are discussed on the basis of biological parameters, mainly heart rate variability (HRV) and brain-derived neurotrophic factor (BDNF), which are crucial to the stress response system. It emerges that instead of finding one specific discriminating marker, future research should rather concentrate on elaborating indices for burnout and depression which integrate combinations of parameters found in genetics, neurobiology, physiology and environment

Burnout und Neurasthenie – Zeitdiagnosen der Jahrhunderte?

Das Burnout-Syndrom hat sich nach seiner Erstbenennung 1974 durch den amerikanischen Psychologen Herbert Freudenberger zu einer wahren Modediagnose unserer Zeit entwickelt und scheint eines der wenigen gesellschaftlich akzeptierten psychischen Krankheitsbilder zu sein. Jedoch lässt sich im Verlauf der Psychiatriegeschichte bereits im 19. Jahrhundert ein Krankheitsbild mit äusserst ähnlicher Erscheinungsform, nämlich dem Leitsymptom der «reizbaren Schwäche», unter dem Namen «Neurasthenie» auffinden. Im vorliegenden Artikel soll überprüft werden, ob es sich bei Burnout-Syndrom und Neurasthenie um gänzlich unterschiedliche Phänomene handelt, oder ob es nicht vielmehr um epochenspezifische Modediagnosen geht, welche im Laufe der Jahrhunderte jeweils in verschiedenen Begriffen abgebildet werden, obwohl sich dahinter dieselbe Symptomatik und Ätiologie verbirgt

Exploring the effectiveness of a specialized therapy programme for burnout using subjective report and biomarkers of stress.

The increasing prevalence of stress-related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single-group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy-one in-patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)-10 were included in the study. In addition to symptomatology, the stress-responsive biomarkers heart rate variability (HRV) and serum brain-derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6-week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered

Human PBMC cultures are susceptible to productive infection by XMRV.

<p>(A) Detection of proviral XMRV sequences by nested PCR in DNAs of PBMC from 5 CSF patients (lanes 1–5) and 5 healthy donors (HD, lanes 6–10) infected for a week with DNase I treated (left hand panel) or DNase I treated and heat-inactivated (right hand panel) supernatants from the XMRV producing 22Rv1 cell line. The no template control (NTC) is in lane 11. DNA prepared from 22Rv1 cells was used as a positive control (lane 12, left panel). Results of a single round PCR for GAPDH are depicted underneath. (B) On the day of DNA isolation, supernatants from the infected PBMC cultures were used to test for virus transmission to LNCaP indicator cells. The results of a nested XMRV PCR with DNA prepared from the exposed LNCaP cells a week after incubation with the PBMC supernatants are shown (lanes 1–10). The control set up was the same as described above (lanes 11 and 12). M  = 100 bp marker. The entire experiment has been repeated twice with similar results.</p

Diagnostic PCR of activated PBMC from CFS and MS patients and healthy donors.

<p>Representative results of nested XMRV PCRs with template DNAs from activated PBMCs after 7 days of culture. Samples from 5 CFS patients (lanes 1–5), 5 MS patients (lanes 6–10) and 5 healthy donors (HD, lanes 11–15) are shown. 200 ng of human genomic DNA spiked with 14 pg of 22Rv1 DNA (genome equivalent of approximately two cells) were used as positive control (lane 16). Results of corresponding single round PCRs for GAPDH as control for DNA integrity and absence of PCR inhibitors are shown in the lower panel. M  = 100 bp marker.</p

Lack of infection of XMRV susceptible LNCaP cells by co-culture with activated PBMCs.

<p>PCR results with isolated LNCaP cell DNA after co-culture with PBMCs from CFS patients (lane 1–5) and healthy donors (lanes 6–10). Five representative samples out of 10 co-cultures for each group are shown. As control, LNCaP cells were infected with XMRV-containing supernatant from 22Rv1 cells (lane 12). A water-only control (no template control, NTC) was run in lane 11. Results of the GAPDH PCR with the same samples are shown in the lower panel. M  = 100 bp marker.</p

Serological assays.

<p>ELISAs with recombinant XMRV proteins were used to detect specific humoral responses. The cut-off was calculated as the mean of all sera from healthy controls plus three times the standard deviation. (A) Results of an XMRV Env antibody ELISA with sera from 36 CFS patients and 17 healthy controls (upper panel) and 112 MS patients and 10 healthy controls (lower panel) identified after unblinding. Sera were incubated at a dilution of 1∶200. (B) Titration of positive control goat sera versus recombinant Gag protein captured by the monoclonal anti-MLV Gag antibody R187. (C) Capture ELISA for the detection of XMRV anti-Gag antibodies in CFS (upper panel) and MS (lower panel) patient sera and healthy controls (gray bars in both panels). Human sera were diluted 1∶200 in blocking buffer.</p