[Psychosocial care of refugees in Germany : Insights from the emergency relief and development aid]. / Psychosoziale Versorgung von Flüchtlingen in Deutschland : Erkenntnisse aus der Not- und Entwicklungshilfe.

Approximately 1.2 million refugees have arrived in Germany since autumn 2014. They are often appraised as being a challenge for the German healthcare system because the acute need for healthcare support was large and appeared suddenly while at the same time resources were limited. This situation was previously unknown for a western European healthcare system, whereas it constitutes a typical challenge for nongovernmental organizations that are active in the field of emergency relief and development aid and that have developed a large number of successful intervention concepts. Of central importance in this context are the basic principles of equal rights, participation of those affected, the principle of nonmaleficence, the resource orientation instead of a deficit orientation as well as the need for integrated and stepped care models. These can serve as general principles not only in the setting of development aid in crisis areas worldwide but also in the health services provided to refugees in the current situation in Germany.

Should early improvement be re-defined to better predict the maintenance of response in first-episode schizophrenia patients?

OBJECTIVE: To evaluate the predictive validity of early response in first-episode schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff to the currently proposed early response definition (20% improvement by week 2). METHOD: Receiver operator characteristic (ROC) analyses were used to identify the predictive validity of the psychopathological improvement of treatment from week 1 to week 8, regarding the maintenance of response until week 52 as well as to define the most reasonable cutoff in 132 first-episode patients. The Youden Index (maximum of sensitivity and specificity) was used to compare the newly developed and the commonly used early response definition. RESULTS: Starting with week 6, a reasonable validity to predict the maintenance of response was found (area under the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score improvement. Using this cutoff 74 patients (56%) were correctly identified to become responder and maintain response during follow-up (sensitivity: 0.747). The Youden Index was higher applying the newly developed early response cutoff featuring higher specificity compared to the commonly used early response definition. CONCLUSION: Regarding long-term treatment, it seems more appropriate to base predictions of the patient's maintenance of response not before 6 weeks of treatment.

Impact of beta-amyloid-specific florbetaben PET imaging on confidence in early diagnosis of Alzheimer's disease.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) may be corroborated by imaging of beta-amyloid plaques using positron emission tomography (PET). Here, we performed an add-on questionnaire study to evaluate the relevance of florbetaben imaging (BAY 949172) in diagnosis and consecutive management of probable AD patients. METHODS: AD patients with a clinical diagnosis in accordance with the NINCDS-ADRDA criteria or controls were imaged using florbetaben. Referring physicians were asked on a voluntary basis about their confidence in initial diagnosis, significance of PET imaging results, and their anticipated consequences for future patient care. RESULTS: 121 questionnaires for probable AD patients and 80 questionnaires for controls were evaluated. In 18% of patients who had initially received the diagnosis of probable AD, PET scans were rated negative, whereas in controls 18% of scans were positive. An increase in confidence in the initial diagnosis was frequently reported (80%). Imaging results had a significant impact on the intended patient care, as judged by the referring physicians; this was most prominent in those patients with a contradicting scan and/or a low confidence in the initial diagnosis. CONCLUSION: Florbetaben amyloid imaging increases the overall confidence in diagnosis of AD and may frequently influence clinical decisions and patient management.

Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study.

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins alpha and beta (sAPP alpha and sAPP beta) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examination >or=20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloid beta peptides, Tau and phospho-Tau. sAPP alpha and sAPP beta were measured with multiplexing method based on electrochemiluminescence. sAPP alpha and sAPP beta CSF concentrations correlated with each other with very high correlation ratio (R=0.96, P<0.001). We observed highly significantly increased sAPP alpha and sAPP beta CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPP alpha and sAPP beta highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPP alpha: cutoff, 117.4 ng ml(-1), sensitivity, 68%, specificity, 85%, P<0.001; sAPP beta: cutoff, 181.8 ng ml(-1), sensitivity, 75%, specificity, 85%, P<0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPP alpha and sAPP beta might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

Comparison of immunosorbent assays for the quantification of biomarkers for Alzheimer's disease in human cerebrospinal fluid.

BACKGROUND: The clinical diagnosis of Alzheimer's disease in early stages may be substantiated by the quantification of the biomarkers Abeta42, Abeta40 and total-Tau (t-Tau) in cerebrospinal fluid (CSF). Different commercially available immunosorbent assays yield reliable results, yet the absolute values obtained may differ in between tests. METHODS: We used CSF samples from patients that reported to our memory clinic. Enzyme-linked immunosorbent assays obtained from Innogenetics were used for the quantification of Abeta42 and t-Tau, test kits from IBL International were used to determine Abeta42 and Abeta40 concentrations. The multiplex assay system obtained from Mesoscale Discovery (MSD) Systems was used for the quantification of all three biomarkers. RESULTS: For all biomarkers, the absolute values obtained with different test systems differ. However, the data sets highly correlate for all comparisons, with the MSD test system proving to be slightly more sensitive. Correlation coefficients (c) for the Abeta42 and Abeta40 quantifications lie between c = 0.80 and c = 0.87, and for the t-Tau quantifications we determined c = 0.99. CONCLUSION: We conclude that all assays evaluated give reliable results, yet absolute values obtained have to be assessed differently within the framework of diagnostic procedures, depending on the system used.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

Relationship between baseline severity of depression and antidepressant treatment outcome.

INTRODUCTION: Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. METHODS: This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. RESULTS: Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. DISCUSSION: Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.

[Targeted prevention of posttraumatic stress disorder]. / Prophylaxe der posttraumatischen Belastungsstörung.

Posttraumatic stress disorder (PTSD) is a severe, frequently chronic condition with a high rate of co-morbidity with other psychiatric syndromes. In contrast to the majority of psychiatric disorders, the traumatic event in PTSD constitutes a clearly defined etiological factor. A growing understanding of the mechanisms contributing to the development of PTSD has highlighted the possibilities for early preventive psychological and pharmacological treatment during the so-called golden hours after a traumatic experience. Whereas preliminary evidence suggests that a pharmacological recalibration of the HPA system and cognitive behavioral therapy may be helpful, other frequently used strategies, such as psychological debriefing or benzodiazepine treatment, seem to be largely ineffective, possibly even worsening PTSD symptoms.

[Dementia and depression determine care dependency in Parkinson's disease: analysis of 1,449 outpatients receiving nursing care in Germany]. / Demenz und Depression determinieren Pflegebedürftigkeit bei M. Parkinson : Untersuchung an 1449 Patienten im ambulanten Versorgungssektor in Deutschland.

BACKGROUND: Parkinson's disease (PD) is frequently accompanied by dementia or depression which can aggravate the clinical picture of the disease and increase the risk of care dependency (CD). Little is known about the associations between PD, these neuropsychiatric comorbidities and CD in outpatients. PATIENTS AND METHODS: A nationwide sample of outpatients (n=1,449) was examined by office-based neurologists (n=315) comprising the documentation of the general, neurological status and the degree of CD. The dementia status was clinically rated according to the established DSM-IV criteria. Depression was screened with the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Overall, 18.3% of all patients were care dependent. Even after adjustment for PD severity, patients with depression (OR=2.8; 95% CI 1.8-4.3), dementia (OR=2.7; 95% CI 1.8-4.1) or both (OR=3.9; 95% CI 2.5-60,0) were at higher risk for CD than patients without dementia or depression. Patients aged ≥76 years were fourfold more likely to be care dependent than patients aged ≤65 years (OR=3.5; 95% CI 2.3-5.5). Across all age groups, patients with depression featured the highest increments (from 11.9 to 42.0%). CONCLUSION: The risk for CD is substantially elevated in outpatients with PD when further neuropsychiatric symptoms are present. The data suggest that depression contributes equally to disability as does dementia.

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol.

While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

A critical analysis and discussion of the appropriateness of the schizophrenia consensus remission criteria in clinical pharmaceutical trials.

BACKGROUND: The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS: The Remission in Schizophrenia Working Group's consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS: 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION: The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.

[The German Study on the Epidemiology of Parkinson's Disease with Dementia (GEPAD): more than Parkinson]. / Die "German study on the epidemiology of Parkinson's disease with dementia" (GEPAD): mehr als nur Parkinson.

UNLABELLED: It is unknown, how frequently Parkinson's disease (PD) is complicated by dementia, depression and other neuropsychiatric conditions. An epidemiologic characterisation of the situation in specialised neurologic settings is lacking. The Geman Study on the Epidemiology of Parkinson's Disease with Dementia (GEPAD) isa national representative epidemiological study of n=1449 PD patients in n=315 office-based neurological settings, designed to estimate the prevalence of dementia, depression and other neuropsychiatric conditions in patients with PD of all stages by using standardized clinical assessments. RESULTS: 28.6% met DSM-IV criteria for dementia. 33.6% met criteria for depression and 61% additionally had other clinically significant psychopathological syndromes. Only 29.4% had no neuropsychiatric conditions. GEPAD reveals for the first time comprehensively that the neuropsychiatric burden of PD patients in all stages and even early stages is considerable, posing challenging questions for research and clinical management.

Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer's disease: a multicenter assessment.

OBJECTIVE: To better understand the seemingly contradictory plasma beta-amyloid (Abeta) results in Alzheimer's disease (AD) patients by using a newly developed plasma Abeta assay, the INNO-BIA plasma Abeta forms, in a multicenter study. METHODS: A combined retrospective analysis of plasma Abeta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. RESULTS: Detection modules based on two different amino (N)-terminal specific Abeta monoclonal antibodies demonstrated that Abeta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Abeta42 plasma concentrations. Abeta40 and Abeta42 concentrations varied consistently with the ApoE genotype, while the Abeta42/Abeta40 ratio did not. Irrespective of the decrease of the Abeta42/Abeta40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). CONCLUSION: A highly robust assay for repeatedly measuring Abeta forms in plasma such as INNO-BIA plasma Abeta forms might be a useful tool in a future risk assessment of AD.

Cerebrovascular reactivity in depressed patients without vascular risk factors.

INTRODUCTION: Cerebrovascular reactivity (CVR) seems to be gaining importance as a prognostic factor for stroke risk. CVR reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus; this mechanism plays an important role in maintaining a constant cerebral blood flow. Evaluating factors that influence CVR will help prevention or early detection of cerebrovascular disease (CVD). In this study we aimed to measure the CVR in vascular-risk free depressed individuals so as to evaluate the effect depression has on CVR and hence its role as a stroke risk factor. METHODS: Using acetazolamid (ACZ) stimulation, CVR was assessed with a transcranial Doppler ultrasound in 25 non-smoking depressed patients (average age: 48.48 +/- 14.40) and in 25 healthy non-smoking controls (average age: 46.76 +/- 13.69) by calculating the difference between the maximal mean blood flow velocity at baseline and the maximal mean blood flow velocity after ACZ stimulation. RESULTS: Basal Cerebral Blood flow in Patients was 50.6 cm/s (SD: 11.6) versus controls 52.80 cm/s (SD: 12.70) whereas after stimulation maximal blood flow velocity was 72.64 cm/s (SD: 15.75) in patients versus 80.20 cm/s (SD: 18.43) in controls. In an analysis of covariance we found that cerebrovascular reactivity was significantly reduced in the vascular-risk free depressed sample. Age had a significant influence whereas gender did not. DISCUSSION: Major Depression appears to decrease cerebrovascular reactivity supporting the idea of increased risk for stroke in depressed patients. The mechanisms leading to this phenomenon and its subtle subgroup differences should be further investigated.

Is MAO-B activity in platelets associated with the occurrence of suicidality and behavioural personality traits in depressed patients?

OBJECTIVE: Low platelet monoaminoxidase B (MAO-B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO-B activity in platelets and aspects of suicidality in depressed patients and controls. METHOD: In 87 patients with affective spectrum disorders (58% suffering from a major depressive episode - MDE) the potential association between platelet MAO-B activity and suicidality was examined. Fifty-nine of the patients had committed suicide attempt recently (SA -'suicide attempters'), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA -'non-suicide attempters'). RESULTS: The SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO-B activity did not differ between SA and NA. No systematic correlations existed between MAO-B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO-B activity in SA with a fatal intention of the SA was observed. CONCLUSION: Our findings do not support a consistent association of platelet MAO-B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.

Correlation of CSF- and MRI-Biomarkers and Progression of Cognitive Decline in an Open Label MCI Trial.

BACKGROUND: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug's efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aß 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer's disease (AD). Overall, worsening and disease progression as measured by the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.

Cerebrovascular reactivity over time course in healthy subjects.

INTRODUCTION: Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism for maintaining constant cerebral blood flow. Many pathological conditions are associated with an impaired CVR thus contributing to a higher risk of cerebrovascular disease. Since an impaired CVR might contribute to a cerebrovascular disease if it lasts for a longer period of time, it is of importance to know what the time-course of CVR might be under healthy conditions. METHODS: We investigated CVR in 33 healthy subjects on baseline and on follow-up after 1 to 3 years. CVR was determined by calculating the difference between maximal blood flow velocity after stimulation with acetazolamide and during rest. Blood flow velocities were measured by transcranial Doppler ultrasound. RESULTS: CVR did not differ significantly in a group of healthy persons when reevaluated after 1 to 3 years. Possible influencing factors like age, gender, interval between testing, and smoking did not show a significant influence. DISCUSSION: This is the first study to investigate within-subject-differences in healthy subjects. CVR seems to remain constant under healthy conditions. Even this short period of life-span is of importance because an altered CVR can improve under treatment within weeks. Nevertheless further studies should follow-up longer periods of time.

Inhibition of brain retinoic acid catabolism: a mechanism for minocycline's pleiotropic actions?

OBJECTIVES: Minocycline is a tetracycline antibiotic increasingly recognized in psychiatry for its pleiotropic anti-inflammatory and neuroprotective potential. While underlying mechanisms are still incompletely understood, several lines of evidence suggest a relevant functional overlap with retinoic acid (RA), a highly potent small molecule exhibiting a great variety of anti-inflammatory and neuroprotective properties in the adult central nervous system (CNS). RA homeostasis in the adult CNS is tightly controlled through local RA synthesis and cytochrome P450 (CYP450)-mediated inactivation of RA. Here, we hypothesized that minocycline may directly affect RA homeostasis in the CNS via altering local RA degradation. METHODS: We used in vitro RA metabolism assays with metabolically competent synaptosomal preparations from murine brain and human SH-SY5Y neuronal cells as well as viable human SH-SY5Y neuroblastoma cell cultures. RESULTS: We revealed that minocycline potently blocks RA degradation as measured by reversed-phase high-performance liquid chromatography and in a viable RA reporter cell line, even at low micromolar levels of minocycline. CONCLUSIONS: Our findings provide evidence for enhanced RA signalling to be involved in minocycline's pleiotropic mode of action in the CNS. This novel mode of action of minocycline may help in developing more specific and effective strategies in the treatment of neuroinflammatory or neurodegenerative disorders.

What are depressive symptoms in acutely ill patients with schizophrenia spectrum disorder?

BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.