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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.
Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
This study examined the impact of three clinical psychological variables (non-pathological levels of depression and anxiety, as well as experimentally manipulated mood) on fat and taste perception in healthy subjects. After a baseline orosensory evaluation, ‘sad’, ‘happy’ and ‘neutral’ video clips were presented to induce corresponding moods in eighty participants. Following mood manipulation, subjects rated five different oral stimuli, appearing sweet, umami, sour, bitter, fatty, which were delivered at five different concentrations each. Depression levels were assessed with Beck’s Depression Inventory (BDI) and anxiety levels were assessed via the Spielberger’s STAI-trait and state questionnaire. Overall, subjects were able to track the concentrations of the stimuli correctly, yet depression level affected taste ratings. First, depression scores were positively correlated with sucrose ratings. Second, subjects with depression scores above the sample median rated sucrose and quinine as more intense after mood induction (positive, negative and neutral). Third and most important, the group with enhanced depression scores did not rate low and high fat stimuli differently after positive or negative mood induction, whereas, during baseline or during the non-emotional neutral condition they rated the fat intensity as increasing with concentration. Consistent with others’ prior observations we also found that sweet and bitter stimuli at baseline were rated as more intense by participants with higher anxiety scores and that after positive and negative mood induction, citric acid was rated as stronger tasting compared to baseline. The observation that subjects with mild subclinical depression rated low and high fat stimuli similarly when in positive or negative mood is novel and likely has potential implications for unhealthy eating patterns. This deficit may foster unconscious eating of fatty foods in sub-clinical mildly depressed populations.
In the partnership between the medical departments of Würzburg University, Germany, and Nagasaki University, Japan, palliative care is a relevant topic. The aim of the study was to perform a comparative analysis of the hospital-based palliative care teams in Würzburg (PCT-W) and Nagasaki (PCT-N). Survey of staff composition and retrospective analysis of PCT patient charts in both PCTs were conducted. Patients self-assessed their symptoms in PCT-W and in Radiation Oncology Würzburg (RO-W). The (negative) quality indicator ‘percentage of deceased hospitalised patients with PCT contact for less than 3 days before death’ (Earle in Int J Qual Health Care 17(6):505–509, 2005) was analysed. Both PCTs follow a multidisciplinary team approach. PCT-N saw 410 cancer patients versus 853 patients for PCT-W (22.8% non-cancer patients). The Eastern Cooperative Oncology Group Performance Status at first contact with PCT-N was 3 or 4 in 39.3% of patients versus 79.0% for PCT-W. PCT-N was engaged in co-management longer than PCT-W (mean 20.7 days, range 1–102 versus mean 4.9 days, range 1–48). The most frequent patient-reported psychological symptom was anxiety (family anxiety: 98.3% PCT-W and 88.7% RO-W, anxiety 97.9% PCT-W and 85.9% RO-W), followed by depression (98.2% PCT-W and 80.3% RO-W). In 14 of the 148 deceased patients, PCT-N contact was initiated less than 3 days before death (9.4%) versus 121 of the 729 deceased PCT-W patients (16.6%). Psychological needs are highly relevant in both Germany and Japan, with more than 85% anxiety and depression in patients in the Japanese IPOS validation study (Sakurai in Jpn J Clin Oncol 49(3):257–262, 2019). This should be taken into account when implementing PCTs.
Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.
Background:
Cancer patients often suffer from psychological symptoms and need psychological support. Especially during the COVID-19 pandemic, eHealth interventions might be helpful to overcome the obstacles of the pandemic. This study evaluates the effectiveness of a video sequence-based eHealth intervention on anxiety, fatigue, and depression in cancer patients.
Methods:
Patients (N = 157) with different tumor entities were randomly assigned to the video intervention group (IG) and the waiting control group (CG). Patients in the IG received a video intervention comprising 8 video sequences over 4 weeks. The videos included psychoeducation on distress and psychological symptoms, Acceptance and Commitment Therapy elements, and Yoga and Qigong exercises. Patients’ anxiety and fear of progression (primary outcomes) and secondary outcomes were assessed before randomization (T1) and after the end of the intervention for IG or the waiting period for CG (T2) using self-reported questionnaires (GAD-7, PA-F-KF, EORTC QLQ-FA12, PHQ-8).
Results:
Patients of the IG showed no significant improvement in anxiety (GAD-7; P = .75), fear of progression (FoP-Q-SF; P = .29), fatigue (EORTC QLQ-FA12; P = .72), and depression (PHQ-8; P = .95) compared to patients in the waiting CG. However, symptoms of anxiety, fatigue, and depression decreased in both groups. Exploratory subgroup analysis regarding sex, therapy status, therapy goal, and tumor entity showed no effects. Overall, the intervention had a high level of acceptance.
Conclusions:
The video intervention was ineffective in reducing the psychological burden compared to a waiting CG. The findings support prior observations of the value of therapeutic guidance and promoting self-management for improving patients’ psychological burdens. Further studies are required to evaluate the effectiveness of psycho-oncological eHealth delivered through video sequences.
Background
In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts.
Methods and Findings
Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male).
Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 /(number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the \(\chi\)\(^{2}\)-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts.
Findings Main Results
Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects and poisoning by substances other than drugs. Median age at time of suicidal behaviour (35-44 years) did not differ between males and females. The overall gender difference in lethality of suicidal behaviour was explained by males choosing more lethal suicide methods (odds ratio (OR) = 2.03; 95% CI = 1.65 to 2.50; p < 0.000001) and additionally, but to a lesser degree, by a higher lethality of suicidal acts for males even within the same method (OR = 1.64; 95% CI = 1.32 to 2.02; p = 0.000005). Results of a regression analysis revealed neither age nor country differences were significant predictors for gender differences in the lethality of suicidal acts. The proportion of serious suicide attempts among all non-fatal suicidal acts with known intentionality (NFSAi) was significantly higher in men (57.1%; 1,207 of 2,115 NFSAi) than in women (48.6%; 1,508 of 3,100 NFSAi) (\(\chi\)\(^{2}\) = 35.74; p < 0.000001).
Main limitations of the study
Due to restrictive data security regulations to ensure anonymity in Ireland, specific ages could not be provided because of the relatively low absolute numbers of suicide in the Irish intervention and control region. Therefore, analyses of the interaction between gender and age could only be conducted for three of the four countries. Attempted suicides were assessed for patients presenting to emergency departments or treated in hospitals. An unknown rate of attempted suicides remained undetected. This may have caused an overestimation of the lethality of certain methods. Moreover, the detection of attempted suicides and the registration of completed suicides might have differed across the four countries. Some suicides might be hidden and misclassified as undetermined deaths.
Conclusions
Men more often used highly lethal methods in suicidal behaviour, but there was also a higher method-specific lethality which together explained the large gender differences in the lethality of suicidal acts. Gender differences in the lethality of suicidal acts were fairly consistent across all four European countries examined. Males and females did not differ in age at time of suicidal behaviour. Suicide attempts by males were rated as being more serious independent of the method used, with the exceptions of attempted hanging, suggesting gender differences in intentionality associated with suicidal behaviour. These findings contribute to understanding of the spectrum of reasons for gender differences in the lethality of suicidal behaviour and should inform the development of gender specific strategies for suicide prevention.
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.
Background
Empirical studies investigating the prevalence of mental disorders and psychological distress in cancer patients have gained increasing importance during recent years, particularly with the objective to develop and implement psychosocial interventions within the cancer care system. Primary purpose of this epidemiological cross-sectional multi-center study is to detect the 4-week-, 12-month-, and lifetime prevalence rates of comorbid mental disorders and to further assess psychological distress and psychosocial support needs in cancer patients across all major tumor entities within the in- and outpatient oncological health care and rehabilitation settings in Germany.
Methods/Design
In this multicenter, epidemiological cross-sectional study, cancer patients across all major tumor entities will be enrolled from acute care hospitals, outpatient cancer care facilities, and rehabilitation centers in five major study centers in Germany: Freiburg, Hamburg, Heidelberg, Leipzig and Würzburg. A proportional stratified random sample based on the nationwide incidence of all cancer diagnoses in Germany is used. Patients are consecutively recruited in all centers. On the basis of a depression screener (PHQ-9) 50% of the participants that score below the cutoff point of 9 and all patients scoring above are assessed using the Composite International Diagnostic Interview for Oncology (CIDI-O). In addition, all patients complete validated questionnaires measuring emotional distress, information and psychosocial support needs as well as quality of life.
Discussion
Epidemiological data on the prevalence of mental disorders and distress provide detailed and valid information for the estimation of the demands for the type and extent of psychosocial support interventions. The data will provide information about specific demographic, functional, cancer- and treatment-related risk factors for mental comorbidity and psychosocial distress, specific supportive care needs and use of psychosocial support offers.
For the current study the Lazarian stress-coping theory and the appendant model of psychosocial adjustment to chronic illness and disabilities (Pakenham, 1999) has shaped the foundation for identifying determinants of adjustment to ALS. We aimed to investigate the evolution of psychosocial adjustment to ALS and to determine its long-term predictors. A longitudinal study design with four measurement time points was therefore, used to assess patients' quality of life, depression, and stress-coping model related aspects, such as illness characteristics, social support, cognitive appraisals, and coping strategies during a period of 2 years. Regression analyses revealed that 55% of the variance of severity of depressive symptoms and 47% of the variance in quality of life at T2 was accounted for by all the T1 predictor variables taken together. On the level of individual contributions, protective buffering, and appraisal of own coping potential accounted for a significant percentage in the variance in severity of depressive symptoms, whereas problem management coping strategies explained variance in quality of life scores. Illness characteristics at T2 did not explain any variance of both adjustment outcomes. Overall, the pattern of the longitudinal results indicated stable depressive symptoms and quality of life indices reflecting a successful adjustment to the disease across four measurement time points during a period of about two years. Empirical evidence is provided for the predictive value of social support, cognitive appraisals, and coping strategies, but not illness parameters such as severity and duration for adaptation to ALS. The current study contributes to a better conceptualization of adjustment, allowing us to provide evidence-based support beyond medical and physical intervention for people with ALS.