Psychological Distress During the COVID-19 Pandemic in Patients With Mental or Physical Diseases.

The coronavirus disease 2019 (COVID-2019) and the consequences of the pandemic on individuals' social, economic, and public lives are assumed to have major implications for the mental health of the general population but also for patients already diagnosed with psychological disorders. The aim of the present study was to investigate the psychological distress during the COVID-19 pandemic in patients with psychological disorders or physical health conditions in inpatient mental and physical treatment programs. A total 2710 patients completed COVID-19 related questions concerning their psychological distress and financial burden during the pandemic. Patients with psychological disorders reported the highest level of psychological distress and financial burden compared to patients with physical health conditions. Furthermore, most patients with psychological disorders attributed their individual psychological distress to the COVID-19 pandemic. In comparison to patients with physical health conditions, patients with psychological disorders are more strongly impacted by the COVID-19 pandemic and have an additional need for psychological/psychotherapeutic treatment due to the COVID-19 crisis. The findings stress the importance of continuous psychosocial support and availability of psychosocial support services for patients with psychological disorders during the pandemic.

Relationship between psychological stress and metabolism in morbidly obese individuals.

BACKGROUND: Despite evidence for a bidirectional relationship between obesity and stress-related mental disorders, the general relationship between psychological stress and metabolism is still controversial. Only few studies have addressed this relationship in morbidly obese individuals. METHODS: The present study investigated the relationship between psychological distress, health-related quality of life (HRQL), eating behavior, negative emotions and body mass index (BMI), body composition and biomedical parameters of metabolism in an adult sample of 123 (94 females) morbidly obese individuals. RESULTS: No significant relationship was found between psychological distress and BMI, body composition or any of the parameters of metabolism; however, there was a strong and robust association between HRQL in the physical domain and BMI, body composition and several biomedical parameters of sugar and fat metabolism. The results also showed an interesting dissociation in the relationship between BMI and HRQL in the physical and psychology domains. Only little evidence was found for a relationship between eating behavior (e.g. restraint) or negative emotions (e.g. anger) and BMI, body composition and parameters of metabolism. There was, however, a significant gender difference in restraint eating. Other commonly reported gender differences in BMI, body composition, fat metabolism and liver values were also observed in this sample of morbidly obese individuals. CONCLUSION: Results from the present study highlight the relationship between HRQL in the physical domain and metabolism. Implications of these findings for weight loss treatment are discussed, emphasizing HRQL as an important treatment goal and the need for long-term psychological monitoring.

Psychopharmacological treatment of patients with borderline personality disorder: comparing data from routine clinical care with recommended guidelines.

Objectives: Borderline personality disorder (BPD) is a life-threatening mental disorder. Guideline recommendations for pharmacological treatment of patients with BPD vary widely. The objective of the present study was to investigate pharmacotherapy of BPD patients in a routine clinical care setting. Methods: Data on the pharmacological treatment of 110 patients (90% female) with BPD (F- 60.3), treated in an inpatient psychiatric-psychosomatic clinic in Austria were assessed. Results: Results show that clinicians frequently prescribe psychotropic medications to patients with BPD, in many cases multiple medications. The most commonly prescribed substance groups were antipsychotics, mood stabilisers and antidepressants. The most commonly prescribed individual drugs were Quetiapine, Lamotrigine and Setraline. There was no significant difference in the different types or overall number of medications prescribed to BPD patients with vs. without comorbid diagnoses. Pharmacotherapy was not related to comorbidity. Conclusions: The present study shows that in routine clinical care settings psychotropic medications are frequently prescribed to patients with BPD, very often resulting in polypharmacy. A positive association between the number of medications and the effectiveness of the inpatient treatment program, as well as the absence of a relationship between number of medications and comorbidity contradicts the often suggested iatrogenic effect of polypharmacy. Key points Guidelines for pharmacotherapy of borderline personality disorders lack consensus Yet, clinicians frequently prescribe psychotropic medications to BPD patients Types/number of medications prescribed to patients with vs. without comorbidities are similar Larger treatment effects are observed for patients with greater numbers of medications Further knowledge is needed about how and why clinicians prescribe medications.

[Meta-analysis of evaluation results of psychiatric-psychosomatic rehabilitation in Austria]. / Meta-Analyse der Evaluationsergebnisse psychiatrischer-psychosomatischer Rehabilitation in Österreich.

OBJECTIVE: Since previous meta-analyses of psychiatric-psychosomatic rehabilitation only rarely included studies from Austrian rehabilitation clinics a systematic review with meta-analysis of previously available evaluation results from Austrian rehabilitation clinics should be conducted. METHODS: A systematic literature search in several data bases (Psyndex, PsycInfo, MEDLINE, Pubmed) and additional manual search was conducted. Evaluation results from the most commonly used assessment instruments (SCL-90/BSI, BDI, WHOQOL-BREF, GAF) were extracted from the studies included and subsequently a meta-analysis was calculated with the extracted data (pre-post comparison). RESULTS: 12 publications with 9 studies from 6 different Austrian rehabilitation clinics could be included in the meta-analysis, with a total of 9329 patients. Results show a significant improvement from pre- to post assessment in the medium effect size range, with a Hedges' g of 0.53 (95%-confidence interval [0.45;0.60]) for improvement in global symptom severity, a Hedges' g of 0.59 (95%-confidence interval [0.54;0.63]) for improvement in subjective quality of life and a Hedges' g of 1.00 (95%-confidence interval [0.83;1.18]) for improvement in global functioning. The effects are robust and there is no evidence for distortion or publication bias. CONCLUSIONS: On average medium effect sizes have been previously achieved with psychiatric-psychosomatic rehabilitation in Austrian rehabilitation clinics. This is comparable with the previous results of rehabilitation clinics in Germany. However, since only one controlled study is available thus far it can not be ruled out that the effects in comparison to no rehabilitation might turn out smaller. Thus, in the future increasingly controlled studies should be conducted and the quality of conducted studies should be improved.

[Relevance of type of diagnosis and occupational status for the results of psychiatric rehabilitation]. / Relevanz von Erkrankungsart und beruflichem Status für die Ergebnisse psychiatrischer Rehabilitation.

OBJECTIVE: The specific effectiveness of psychiatric rehabilitation has been confirmed in numerous studies. Of particular interest is to what extend different results can be observed regarding the occupational status and type of mental illness of patients. Unemployment at the start of treatment is generally deemed to be a disadvantage for treatment outcome. Weaker treatment effects have also been reported for some types of mental illnesses, such as pain- und somatoform disorders. METHODS: Results from the evaluation of a sample of 2260 patients form the psychiatric rehabilitation clinic Gars am Kamp were analyzed, with regard to the occupational status and type of mental illness of patients. Changes in general symptom severity, quality of life and functioning were assessed. RESULTS: Regarding the occupational status, overall unemployed patients suffered from higher degrees of global symptom severity and the lower levels of global quality of life compared to employed and retired patients. However, improvements in the course of rehabilitative treatment could be observed regardless of the occupational status of patients. Regarding the type of mental illness, overall patients with burnout (Z73.0) reported the lowest levels of global symptom severity and highest degree of global quality of life. In comparison patients with somatoform disorders (F45) showed the lowest degree of global quality of life. However, positive treatment effects regarding general symptom severity and health related quality of life could be observed regardless of the type of mental illness (diagnosis) of patients. In respect to the improvement of global functioning small differences in absolute treatment effects were detected depending on the type of diagnosis of patients. However, relative treatment effects in respect to global functioning were comparable for all types of diagnosis. CONCLUSIONS: Improvements in the course of rehabilitative treatment regarding general symptom severity, quality of life and global functioning can be obtained independent of occupational status and type of mental illness of patients.

[Changes and differences of heart rate variability of patients in a psychiatric rehabilitation clinic]. / Veränderungen und Unterschiede in der Herzratenvariabilität (HRV) von Patienten einer psychiatrischen Rehabilitationsklinik.

BACKGROUND: A reduced heart rate variability (HRV) has been associated with various different pathological physical and psychological conditions and illnesses. The present study is focused on investigating HRV in respect to psychological disorders (depressive disorders anxiety disorders, Burn-out-Syndrome). METHODS: The results from an investigation with patients from a psychiatric Rehabilitation clinic following a six week in-patient treatment are presented. RESULTS: The results show relevant changes in HRV in the course of the rehabilitative treatment for patients with depressive disorders, anxiety disorders or Burn-out-Syndrome. Simultaneously changes in HRV were linked with improvements in patient's psychological symptoms. Changes in HRV (i. e. an increase of relevant HRV-parameters) were accompanied by a reduction of psychological strain as well as psychological and physical health problems, which typically occur in Burnout-Syndrome. Furthermore, changes in relevant HRV-parameters were predictive of changes in psychological symptoms (depression, anxiety, phobia, Burnout symptoms). CONCLUSIONS: The present study did show, that in respect to the investigation of the relationship between HRV and subjective data, primarily those HRV-parameters are important (in terms of significant results) which are based on parasympathetic activity. These results are interesting in the context of theories, which view vagal mediated HRV as positively connected with self-regulation, adaptability and positive interpersonal interaction of individuals.

Subcortical morphological correlates of impaired clock drawing performance.

The objective of this study was to investigate the associations between clock drawing test (CDT) performance and subcortical brain morphology. Fifty-four participants (21 patients with Alzheimer's disease, 23 with mild cognitive impairment and 10 healthy controls) underwent neuropsychological assessment and high-resolution magnetic resonance imaging at 3T. CDT performance was related to volume and shape measurements of amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus, respectively. Impaired CDT performance was correlated with alterations predominantly in the hippocampus bilaterally and in the right globus pallidus. These associations referred to regionally specific morphometric alterations rather than to global atrophy of the respective structures. Our findings support an involvement of subcortical brain regions in CDT performance.

ß-Amyloid (1-42) Levels in Cerebrospinal Fluid and Cerebral Atrophy in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Recent studies consistently reported Alzheimer's disease (AD) and, to a lower extent, mild cognitive impairment (MCI) to be accompanied by reduced cerebrospinal fluid (CSF) levels of ß-amyloid. However, how these changes are related to brain morphological alterations is so far only partly understood. METHODS: CSF levels of ß-amyloid (1-42) were examined with respect to cerebral atrophy in 23 subjects with MCI, 16 patients with mild-to-moderateAlzheimer's disease (AD) and 15 age-matched controls by using magnetic resonance imaging and voxel-based morphometry (VBM). RESULTS: When contrasted with the controls, ß-amyloid (1-42) levels were significantly lower (p < 0.05) in patients with MCI and even more so in the AD patients. This effect was significantly associated with reduced gray matter densities in both the right and left hippocampal head based on the results of a VBM analysis across the entire sample. CONCLUSION: Our finding confirms the results of previous studies and suggests that both the decrease in ß-amyloid (1-42) and the development of hippocampal atrophy coincide in the disease process.

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.

BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid ß (Aß)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. METHODS: The program is open for laboratories using commercially available kits for Aß, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. RESULTS: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aß-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aß triplex (AßN-42, AßN-40, and AßN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. CONCLUSIONS: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

Amyloid in skin and brain: what's the link?

For too long, amyloids have been under general suspicion to merely cause diseases. In recent years, we have learned that these interesting proteins may also fulfill important biological tasks. Moreover, recent publications show emerging evidence for a so-called brain-skin axis. This viewpoint paper aims to address the question what is known about the link between brain and skin based on the literature available for two diseases caused by amyloid formation: Alzheimer's disease (AD) and cutaneous amyloidoses. In addition, we acquaint the reader with a different perspective on the role of amyloid in skin and brain.

Skin and brain age together: The role of hormones in the ageing process.

The importance of the endocrine environment in the initiation of the ageing process has been elucidated in several in vivo and in vitro studies. Changes in endocrine pathways accompany healthy ageing, these include the growth hormone/insulin-like growth factor-I axis (somatopause) and that of sexual hormones, namely estradiol (menopause), testosterone (andropause), and dehydroepiandrosterone and its sulphate (adrenopause). The clinical significance of these changes is variable and results in morphological and functional alterations of all organ systems including the skin and the central nervous system. Moreover, the pathogenesis of age-associated diseases such as epithelial skin cancer and neurodegenerative diseases has been partly attributed to the lack of hormones. Several studies have been conducted in an attempt to reverse the ageing process and clinical signs by substitution of the serum hormone levels in older individuals, however the benefits of hormone replacement therapy, if any, are still controversial. On the other hand, recent data suggest that skin is a window to the human organism and represents an adequate model for ageing research, also implying the use of skin samples for evaluating the ageing status of the central nervous system.

Cerebrospinal fluid concentrations of functionally important amino acids and metabolic compounds in patients with mild cognitive impairment and Alzheimer's disease.

Cerebrospinal fluid (CSF) biomarkers play an important role in the differential diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and its postulated precursor stage mild cognitive impairment (MCI). While CSF tau protein, phospho-tau protein and beta-amyloid have become part of the diagnostic process in clinical routine, the importance of several other biomarkers remains quite unclear. Among these, amino acids and metabolic compounds have been studied in clinical conditions mostly other than AD and, to our knowledge, never in MCI. In patients with AD (n = 14) and MCI (n = 13) we now determined CSF levels of 36 different amino acids and metabolic compounds by high-performance liquid chromatography. We found that 8 out of 36 amino acids (urea, threonine, glutamate, citrulline, alpha-aminobutyric acid, ornithine, ammonia and arginine) were significantly elevated in the CSF of patients with AD compared to those with MCI. As most of these amino acids and metabolic compounds are functionally important for brain-specific metabolic processes, neurotransmitter pathways or compensatory mechanisms, our findings might reflect these changes occurring within the brain of patients with MCI and those who developed manifest AD.

CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.

CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.

Association of total tau and phosphorylated tau 181 protein levels in cerebrospinal fluid with cerebral atrophy in mild cognitive impairment and Alzheimer disease.

BACKGROUND: We sought to examine the association of levels of total tau (t-tau) and phosphorylated tau 181 (p-tau181) protein with brain morphology in mild cognitive impairment, as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer disease. METHODS: Twenty-three participants with AACD, 16 with Alzheimer disease and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. We performed voxel-based morphometry to investigate the association between tau levels in cerebrospinal fluid (CSF) and cerebral grey matter density throughout the entire brain. RESULTS: Voxel-based morphometry revealed that both elevated t-tau and p-tau181 concentrations were associated with reduced grey matter density in temporal, parietal and frontal regions. Among participants with AACD, elevated levels of p-tau181 (but not t-tau) in CSF were correlated with a pronounced atrophy in the right hippocampus. LIMITATIONS: Our study was limited by the small sample, especially with respect to the analysis comprising the AACD subgroups. Moreover, we did not correct our voxel-based morphometry analyses for multiple dependent comparisons, therefore they harbour a risk of false-positive results. CONCLUSION: Elevated levels of t-tau and p-tau181 in CSF reflect degenerative processes in the cortical regions typically affected in Alzheimer disease. Our findings in participants with AACD support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early Alzheimer disease.

Novel systemic markers for patients with Alzheimer disease? - a pilot study.

Almost 2% of the population of western industrialized countries are affected by Alzheimer's disease (AD). Nevertheless the pathogenetic process leading to this neurodegenerative disease is widely unknown. Thus, we focus on novel pathophysiological aspects of AD. We hypothesize that AD patients reveal increased levels of peripheral blood mononuclear cells (PBMCs) expressing proinflammatory (COX-2, TNF-alpha, CD40), proapoptotic (PARP-1), adhesion-relevant (CD38) or AD associated (C99, BACE1, Presenilin-1) proteins as well as elevated proinflammatory biochemical plasma parameters. Therefore, PBMCs of AD patients and age-matched control subjects were studied by two color fluorescence-activated cell sorter (FACS) analysis. Furthermore, concentration of plasma oxidized low-density lipoprotein (oxLDL) and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). We found a significantly increased percentage of TNF-alpha, COX-2, PARP-1, CD38, C99 or presenilin-1 positive PBMCs in AD patients compared with healthy subjects. FACS analyses revealed that the percentage of C99 or presenilin-1 positive PBMCs, which also express TNF-alpha, COX-2, PARP-1 or CD38 is also increased in AD patients. Additionally, AD patients had significantly increased plasma oxLDL and TNF-alpha levels. Furthermore, we found positive correlations between plasma oxLDL or TNF-alpha concentrations and the percentage of TNFalpha+, COX-2+ or PARP-1+, as well as PS-1+, C99+ or BACE+ PBMCs. Our findings suggest that immunocytological investigations, based on immunophenotyping of AD relevant proteins combined with measurement of proinflammatory, proapoptotic and adhesion-relevant proteins in PBMCs may provide more insight into the pathophysiology of AD.

[CSF levels of total tau protein in patients with mild cognitive impairment and Alzheimer's disease]. / Tauproteinspiegel bei Patienten mit leichter kognitiver Beeinträchtigung und Alzheimer-Demenz.

In recent studies, patients diagnosed with Alzheimer's disease (AD) showed significantly elevated CSF levels of tau protein. Tau protein was therefore regarded as a putative molecular marker for AD. Since early diagnosis of AD is warranted for appropriate therapeutic intervention, investigation of total tau protein levels in patients with Aging Associated Cognitive Decline (AACD) and AD are reasonable. In our study the CSF concentrations of total tau protein were measured by ELISA in 132 patients with AD, 29 patients with AACD and 24 healthy controls. CSF concentrations were compared between the subgroups of mild, moderate and severe AD, AACD and the control group and were correlated with age and severeness of the illness. The concentration of total tau protein was increased significantly in patients with severe and moderate AD compared to all other groups. Within the group of AD patients, total tau protein correlated significantly with the severity of the dementia but not with age. Although the range of the measured tau protein concentrations is wide and overlapping between the diagnostic groups our data indicate that from a clinical point of view significantly increased tau protein levels confirm the clinical diagnosis of AD while normal values do not exclude it.

Influence of delayed CSF storage on concentrations of phospho-tau protein (181), total tau protein and beta-amyloid (1-42).

It is generally accepted that cerebrospinal fluid (CSF) biomarkers such as tau protein, phosphorylated tau protein (threonine 181) and beta-amyloid (1-42) can facilitate early and differential diagnosis of Alzheimer's disease (AD). Since the respective concentrations can only be measured in a number of specialized centers, time to CSF specimen work-up has been considered as crucial for the stability of the respective biomarkers. When shipping of CSF samples is needed for biomarker measurement and immediate freezing of samples is not available, an overnight delay of up to 24h frequently occurs. Therefore, we investigated the potential impact of a 24h delayed freezing on CSF biomarker concentrations and compared it to 2h storage (room temperature, 20 degrees C) and an immediate freezing. First, storage at room temperature for 2h had only marginal, non-significant effects on the concentrations of CSF total tau protein and phospho-tau protein (181) compared to immediate freezing. Second, storage at room temperature for 24h did not significantly affect total tau protein or phospho-tau protein but beta-amyloid (1-42) concentrations which increased significantly compared to the samples frozen immediately. These results indicate that CSF samples for the evaluation of total tau and phospho-tau protein may be kept at room temperature for up to 24h whereas CSF samples for beta-amyloid (1-42) need to be frozen immediately.

Increased tau protein differentiates mild cognitive impairment from geriatric depression and predicts conversion to dementia.

Significantly increased cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated at threonine 181 tau (p-tau) levels were frequently found in patients with mild cognitive impairment (MCI) who have an increased risk of developing Alzheimer's disease (AD). Though MCI often overlaps with depressive symptoms making early diagnosis difficult, to date no CSF marker has been probed to support the differential diagnosis of geriatric major depressive disorder and MCI eventually converting to AD. CSF levels of t-tau and p-tau were determined by ELISA in 80 subjects with MCI (aging associated cognitive decline criteria), 54 patients with major depression and 24 cognitively healthy controls. Patients were reassessed after a follow-up period of at least 12 month. During follow-up, 29% of the MCI patients but only one patient with major depression converted to AD. Already at baseline converters to AD were characterized by significantly higher t-tau and p-tau levels compared to non-converters and the other diagnostic groups. Our findings demonstrate that both, CSF t-tau and p-tau levels facilitate the differential diagnosis of MCI and are of prognostic value.