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Background
Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS).
Methods
Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy).
Results
FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05).
Conclusion
Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.
Major depression (MD) and posttraumatic stress disorder (PTSD) share common brain mechanisms and treatment strategies. Nowadays, the dramatically developing COVID-19 situation unavoidably results in stress, psychological trauma, and high incidence of MD and PTSD. Hence, the importance of the development of new treatments for these disorders cannot be overstated. Herbal medicine appears to be an effective and safe treatment with fewer side effects than classic pharmaca and that is affordable in low-income countries. Currently, oxidative stress and neuroinflammation attract increasing attention as important mechanisms of MD and PTSD. We investigated the effects of a standardized herbal cocktail (SHC), an extract of clove, bell pepper, basil, pomegranate, nettle, and other plants, that was designed as an antioxidant treatment in mouse models of MD and PTSD. In the MD model of “emotional” ultrasound stress (US), mice were subjected to ultrasound frequencies of 16–20 kHz, mimicking rodent sounds of anxiety/despair and “neutral” frequencies of 25–45 kHz, for three weeks and concomitantly treated with SHC. US-exposed mice showed elevated concentrations of oxidative stress markers malondialdehyde and protein carbonyl, increased gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and other molecular changes in the prefrontal cortex as well as weight loss, helplessness, anxiety-like behavior, and neophobia that were ameliorated by the SHC treatment. In the PTSD model of the modified forced swim test (modFST), in which a 2-day swim is followed by an additional swim on day 5, mice were pretreated with SHC for 16 days. Increases in the floating behavior and oxidative stress markers malondialdehyde and protein carbonyl in the prefrontal cortex of modFST-mice were prevented by the administration of SHC. Chromatography mass spectrometry revealed bioactive constituents of SHC, including D-ribofuranose, beta-D-lactose, malic, glyceric, and citric acids that can modulate oxidative stress, immunity, and gut and microbiome functions and, thus, are likely to be active antistress elements underlying the beneficial effects of SHC. Significant correlations of malondialdehyde concentration in the prefrontal cortex with altered measures of behavioral despair and anxiety-like behavior suggest that the accumulation of oxidative stress markers are a common biological feature of MD and PTSD that can be equally effectively targeted therapeutically with antioxidant therapy, such as the SHC investigated here.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients' functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers' burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers' burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients' functional status (r\(_p\) = −0.555, p < 0.001, n = 242). It was influenced by the CGs' own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients' wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs' depression (r\(_p\) = 0.627, p < 0.001, n = 234), anxiety (r\(_p\) = 0.550, p < 0.001, n = 234), and poorer physical condition (r\(_p\) = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients' impairment in daily routine (r\(_s\) = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs' lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs' work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.
Rationale
While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation.
Objective
Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene.
Results
Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{−/−}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{−/−}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{−/−}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{−/−}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner.
Conclusions
Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.
Major depressive disorder (MDD) is a very common stress-related mental disorder that carries a huge burden for affected patients and the society. It is associated with a high mortality that derives from suicidality and the development of serious medical conditions such as heart diseases, diabetes, and stroke. Although a range of effective antidepressants are available, more than 50% of the patients do not respond to the first treatment they are prescribed and around 30% fail to respond even after several treatment attempts. The heterogeneous condition of MDD, the lack of biomarkers matching patients with the right treatments and the situation that almost all available drugs are only targeting the serotonin, norepinephrine, or dopamine signaling, without regulating other potentially dysregulated systems may explain the insufficient treatment status. The hypothalamic-pituitary-adrenal (HPA) axis is one of these other systems, there is numerous and robust evidence that it is implicated in MDD and other stress-related conditions, but up to date there is no specific drug targeting HPA axis components that is approved and no test that is routinely used in the clinical setting identifying patients for such a specific treatment. Is there still hope after these many years for a breakthrough of agents targeting the HPA axis? This review will cover tests detecting altered HPA axis function and the specific treatment options such as glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH1) receptor antagonists, tryptophan 2,3-dioxygenase (TDO) inhibitors and FK506 binding protein 5 (FKBP5) receptor antagonists.
In einer Querschnitt- und einer Längsschnittuntersuchung an insgesamt 95 Multiple Sklerose Patienten wurden in einem semistrukturierten Interview Krankheitsursachen-Vorstellungen (KUV) erfragt. Mit dem BDI wurde die Depressivität erfasst. Im Längsschnitt wurden 24 neu-diagnostizierte Patienten zu drei Zeitpunkten befragt: Gleich im Anschluss (max. 24 Stunden) an die Diagnoseeröffnung, nach 6 Wochen und nach 6 Monaten. Etwa die Hälfte aller Patienten äußerten subjektive Ursachenvorstellungen zu ihrer Erkrankung. In der Längsschnittstudie zeigte sich eine Zunahme der Patienten mit Krankheitsursachen-Vorstellungen, die nach sechs Monaten ebenfalls 50% erreichten. Inhaltlich konnten zwölf Hauptthemen herausgearbeitet werden: Umweltfaktoren, Veranlagung, Strafe, somatische Vorerkrankung, psychische Erkrankung, Schwangerschaft, Überanstrengung, Störung des Immunsystems, labile Persönlichkeit, Stress, Sorgen und Ängste, schlechte Kindheit. Patienten mit Krankheitsursachen-Vorstellungen unterschieden sich weder durch allgemein soziodemographische noch durch krankheitsspezifische Daten. Sie waren jedoch signifikant depressiver. Für die weitere Analyse erfolgte eine Aufteilung der Patienten nach der Art ihrer subjektiven Vorstellung in zwei polare Gruppen mit internal-psychischer versus external-körperlicher KUV. Dabei ließ sich zeigen, dass nicht das Vorhandensein von subjektiven Theorien als solches bereits mit höherer Depressivität einhergeht. Vielmehr sind es allein die Patienten mit internal-psychischen Kausalattributionen, die zu höheren Werten auf der Depressionsskala beitragen. Patienten mit eher external-körperlichen Erklärungsmodellen waren tendenziell sogar weniger depressiv als Patienten ohne KUV. Auch im Längsschnitt erfolgte zunächst analog die Inhaltsanalyse, wobei im Wesentlichen ähnliche Inhaltskategorien gefunden wurden. Anschließend werden die Entwicklung, Dynamik und Konstanz von subjektiven Theorien anhand von Einzelverläufen untersucht: Zehn Patienten hatten nie Krankheitsursachen-Vorstellungen, sieben entwickelten sie erst im Untersuchungszeitraum, sechs hatten Vorstellungen von Anfang an, wobei drei davon einen inhaltlichen Wechsel vollzogen. Als Funktion dieser subjektiven Theorien konnte in zwei Fällen eine komplette Krankheitsverleugnung aufgezeigt werden, in vier Fällen erfüllten die Ursachenvorstellungen Kontrollfunktionen für die Erkrankung. Anschließend werden die Ergebnisse im Kontext des derzeitigen Forschungsstandes diskutiert sowie Probleme der Studie methodenkritisch analysiert. Die Bedeutung von internal-psychischen KUV als möglicher Indikator für Patienten mit Problemen in der Krankheitsverarbeitung wird hervorgehoben. Hieraus werden Ansätze für weiterführende Forschungen sowie für die klinische Betreuung dieser Patienten abgeleitet.
Bei morbider Adipositas (BMI > 40 kg/m²), von der in Deutschland 1,6% der übergewichtigen Frauen und 0,5% der übergewichtigen Männer (BMI > 25 kg/m²) betroffen sind, erweisen sich für eine ausreichende und dauerhafte Gewichtsreduktion nur chirurgische Maßnahmen, wie z.B. laparoskopisches Gastric banding als effektiv. Allerdings fehlen Studien zur langfristigen Effektivität. In der vorliegenden Katamnesestudie zur Langzeiteffektivität von Gastric banding acht Jahre nach stattgefundener Operation wurden Veränderungen in Gewicht, depressiver Symptomatik, Selbstakzeptanz, Essverhalten und aufgetretene Komplikationen untersucht.
Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.
Mental disorders at the beginning of adolescence: Prevalence estimates in a sample aged 11-14 years
(2022)
Objectives
This study aims to provide a deeper insight into mental disorders in early adolescence. We report prevalence rates (mental health problems, depressive symptoms, eating disorders, NSSI, STBs) to be used in future studies and clinical ventures. We also expected to find gender differences, with girls being be more affected than boys are.
Study design
877 adolescents (M = 12.43, SD = 0.65) from seven German high schools completed a series of questionnaires assessing their mental health (SDQ, PHQ-9, SEED, DSHI-9, Paykel Suicide Scale, FAS III).
Methods
We calculated cut-off-based prevalence estimates for mental health issues for the whole sample and compared estimates between genders.
Results
12.5% of the sample reported general mental health problems. The estimated prevalence of depressive symptoms lay at of 11.5%. Additionally, 12.1% and 1.3% of the participants displayed relevant symptoms of anorexia or bulimia nervosa, respectively. A total of 10.8% reported engaging in non-suicidal self-injury (NSSI) at least once in their lifetime, of whom 5.6% reported repetitive NSSI. 30.1% of the participants described suicidal thoughts, 9.9% suicide plans, and 3.5% at least one suicide attempt. Girls were generally more affected than boys, except for bulimia nervosa, suicidal behavior, and partly NSSI.
Conclusion
Our findings corroborate the established relevance of early adolescence for the development of mental health problems and suggest that a substantial proportion of young adolescents suffer from such problems early on. Considering the ongoing COVID-19 pandemic and reported negative mental health consequences, the current findings underline the importance of preventive interventions to avoid the manifestation of mental disorders during adolescence.