Ina Jahn

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

The serotonin transporter availability in untreated early-onset and late-onset patients with obsessive-compulsive disorder.

The pathogenetic role of central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naive OCD patients (36±13 yr, eight females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 yr, nine females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influenced SERT availability measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in LO-OCD (starting at age 18 yr) compared to EO-OCD and HC in limbic (e.g. the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, nucleus accumbens and hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.

Unstable EEG-vigilance in patients with cancer-related fatigue (CRF) in comparison to healthy controls.

Abstract Objectives. Cancer-related fatigue (CRF) is associated with tiredness and sleepiness. It remains unclear, whether such complaints are associated with neurophysiological signs of sleep proneness or a state of neurophysiological hyperarousal in which the patient finds it difficult to relax and to initiate sleep. Therefore the goal of this study is to compare the electroencephalographic (EEG)-vigilance regulation of patients with CRF and healthy controls. Methods. A 15-min resting EEG with eyes closed was recorded in 22 patients with CRF and 22 matched healthy controls. Consecutive 1-s segments were classified into seven different vigilance stages ranging from high alertness to relaxed wakefulness (stage 0, A1, A2, A3) and further on to drowsiness (B1, B2/3) and sleep onset (stage C). Results. Results showed that patients with CRF revealed a higher number of vigilance stages A3 (mean 15.26 vs. 6.67%, P = 0.004) dropped significantly earlier to vigilance levels A3 (drop after 130.8 vs. 533.3 s, P = 0.000) and B2/3&C (407.8 vs. 604.1 s, P = 0.035) and showed significantly more transitions between vigilance stages (46.0 vs. 31.1%, P = 0.003) in comparison to healthy controls. Conclusions. These findings suggest an unstable vigilance regulation in patients with CRF and provide a neurophysiological framework for the reported efficacy of psychostimulants in CRF.

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer's disease

Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which cerebrospinal fluid (CSF) levels are found altered following acute or prolonged neuronal damage. Investigations concerning the role of NSE in Alzheimers disease (AD) are conflicting with both elevated and reduced levels. We measured CSF-levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were significantly elevated in AD (18.12 ng/mL (95% CI 15.63-20.60), HS 8.46 ng/mL (95% CI 5.98-10.94), p=0.00002) and effect size for mean group differences high (1.84). NSE alone (cut-off score 15.80 ng/mL, 94% sensitivity, 97% specificity) and in combination with T-tau and P-Tau had high diagnostic accuracy to differentiate AD from HS. NSE correlated significantly with T-tau (r ≥ 0.87, p<0.000001) and P-tau (r ≥ 0.88, p<0.000001) in both AD and HS. Our results indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD that may be used in supporting AD diagnostics.

Altered EEG lagged coherence during rest in obsessive–compulsive disorder

OBJECTIVE Functional magnetic resonance imaging (fMRI) studies found alterations of functional connectivity in obsessive compulsive disorder (OCD). However, there is little knowledge about region of interest (ROI) based electroencephalogram (EEG) connectivity, i.e. lagged non-linear and linear coherence in OCD. Goal of this study was to compare these EEG measures during rest and at different vigilance stages between patients and healthy controls (HC). METHODS A 15 min resting-state EEG was recorded in 30 unmedicated patients and 30 matched HC. Intracortical lagged non-linear coherence of the main EEG-frequency bands within a set of frontal ROIs and within the default mode network (DMN) were computed and compared using intracortical exact low resolution electromagnetic tomography (eLORETA) software. RESULTS Lagged non-linear but not linear coherence was significantly decreased for patients in comparison to HC for the beta 2 frequency between frontal brain areas but not within the DMN. When analysing separate EEG-vigilance stages, only high vigilance stages yielded decreased frontal phase synchronisation at beta and theta frequencies. CONCLUSIONS The results underline an altered neuronal communication within frontal brain areas during rest in OCD. SIGNIFICANCE These findings encourage further research on connectivity measures as possible biomarkers for physiological homogeneous subgroups.

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder

Abstract Objectives. Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. Methods. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Results. Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95–13.52 95% CI) compared to the controls (6.17 ng/ml (4.55–7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen’s d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7–90.8) and specificity of 75% (95% CI 57.9–86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77–1.48) in MDD, 0.97 ng/ml (0.64–1.30) in controls). Conclusions. Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.

Does "thinking about thinking" interfere with memory? An experimental memory study in obsessive-compulsive disorder.

Neuropsychological assessments of participants with obsessive-compulsive disorder (OCD) indicate impaired verbal memory if to be remembered material has to be organized. People with OCD also tend to focus their attention on their thoughts (heightened cognitive self-consciousness). We tested the hypothesis that cognitive self-consciousness causes verbal memory deficits by provoking a division of attention between study task and thoughts. Thirty-six participants with OCD, 36 matched healthy controls and 36 participants with major depressive disorder (MDD) learned under proactive interference in three study conditions: single-task condition, condition with heightened cognitive self-consciousness and condition with an external secondary task. Memory was impaired in the cognitive self-consciousness condition compared to both other conditions. Independent of condition, participants with OCD showed a reduced memory performance compared to healthy controls, but did not differ from participants with MDD. Our results are in line with the hypothesis that cognitive self-consciousness causes memory impairment.

The impact of attentional and emotional demands on memory performance in obsessive-compulsive disorder

Lower performance on memory tests in obsessive-compulsive disorder (OCD) has been repeatedly observed. However, the origins of these performance deficits are not sufficiently explained. In this study we tested if OCD-related extensive focus of attention on thoughts (heightened self-consciousness) could be an explanatory mechanism for lower memory performance. Heightened situational self-consciousness was manipulated by instructing participants to either monitor neutral thoughts or to monitor OCD-related thoughts. We included a Behavioral Avoidance Task based on individual obsessions and compulsions to induce OCD-related thoughts. Participants were asked to perform these monitoring tasks in parallel to a taxing verbal memory task, resulting in learning under divided attention. The two conditions of learning under divided attention were compared to a single-task condition. Twenty-four participants with OCD and 24 healthy controls took part in these three learning conditions. The results indicate that in both groups memory performance deteriorated in the two conditions with divided attention compared to the single task condition. In the OCD-related thought monitoring condition (OTM) self-consciousness and Behavioral Avoidance Task-induced stress and fear were particularly increased and memory performance further deteriorated in the OCD group. This finding highlights an important and underestimated mechanism (personal involvement) which might serve to better understand lower memory performance in OCD.

Likely impact of the UN Convention on disability on mental health services

Purpose of review After a large majority of UN member states ratified the Convention on the Rights of Persons with Disabilities (UNCRPD), this article aims to provide an overview of its implementation and possible effects in the area of mental health services in individual contract states. Recent findings This article looks at the implementation processes of the UNCRPD in individual industrialized, emerging and developing countries. In addition to changes in national legislation, potential influences on the supply and support systems for persons with mental illness are considered. Positive approaches and efforts are described. Difficulties and barriers that could be responsible for the long process of implementation of the UNCRPD are described, and so is the restructuring and development of adequate supply and support systems in the area of mental healthcare in industrialized, emerging and developed countries. Summary The UNCRPD is a groundbreaking encouragement for various changes in the area of mental health services. The path to subject orientation and individual support structures is long and slow in all countries – in industrialized, emerging and developed countries. National law and health legislation must be adjusted and developed to create an obligatory context for inclusive services required for persons with mental illnesses. Community-based care is prioritized, and this facilitates participation and inclusion.

Geschlechterspezifische Aspekte bei der Inanspruchnahme psychiatrisch-psychotherapeutischer Versorgung

Männer und Frauen sind verschieden – sowohl im Hinblick auf Gesundheit und Gesundheitsverhalten, als auch hinsichtlich Diagnostik, Therapie und Verlauf von Erkrankungen. In den letzten Jahren mehren sich Studien, die auf die Notwendigkeit hinweisen, solche Unterschiede genauer zu untersuchen. Während über viele Jahre unter „Geschlechter-/Genderforschung“ vornehmlich „Frauenund frauenspezifische Forschung“ verstanden wurde, herrscht zunehmend Einverständnis darüber, dass „geschlechterspezifische Analysen und Forschung“ zwingend den Einbezug beider Geschlechter voraussetzen. Die Vernachlässigung der Variable Geschlecht erweist sich nicht zuletzt im Bemühen um eine evidenzbasierteMedizin als ein gravierendes Problem, dabei ist die Frage nach Einfluss und Wirkung des biologischen (engl.: sex) und des sozialen Geschlechts (engl.: gender) eine Querschnittfragestellung und muss im Hinblick auf Versorgung und Forschung gleichermaßen interdisziplinär verfolgt werden. Geschlechtsspezifische Aspekte bei psychischen Störungen sind hinlänglich bekannt. Insbesondere Angaben zu Häufigkeitsunterschieden, etwa bei Depressionen, Angstund Essstörungen bzw. bei Suchterkrankungen sind auch publiziert [1]. Nachwie vor weniger dezidierte geschlechterspezifische Angaben lassen sich im Hinblick auf Diagnosestellung, Behandlungsverlauf oder Art des und Einflüsse auf das Inanspruchnahmeverhalten von Gesundheitsleistungen bei Frauen und Männern finden [2]. Dies interessiert aber, da auch hier relevante Unterschiede vermutet werden können. Zu den umweltbezogenen Einflussgrößen, die zur Modifikation und Verlaufsbeeinflussung von psychischen Erkrankungen beitragen, gehört die Inanspruchnahme von Gesundheitsleistungen. Aus geschlechterspezifischer Sicht ist die unterschiedliche Inanspruchnahme von stationären, ambulanten sowie ärztlichen und nichtärztlichen Gesundheitsleistungen von Frauen und Männern interessant, um Aspekte der Über-, Unterund Fehlversorgung aufzudecken. Dabei können Ergebnisse derart angelegter Studien wichtige Erkenntnisse liefern zu individuellen und kontextbezogenen geschlechterabhängigen Determinanten der Versorgung. Geschlechtersensible Implikationen für die Planung von Ressourcen der Gesundheitsversorgung und Überlegungen für geschlechterdifferente Aspekte des zukünftigen Versorgungsmanagements können davon abgeleitet werden [2]. Erste Ergebnisse aus Untersuchungen zu geschlechterspezifischen Einflüssen auf die Inanspruchnahme von Gesundheitsleistungen bei Zwangsstörungen verweisen auf interessante Aspekte. Patienten mit Zwangsstörungen suchen im Mittel 7–10 Jahre nach Krankheitsbeginn erstmals professionelle Hilfe auf [3, 4] und haben zu diesem Zeitpunkt oft einen hohen Grad an Chronifizierung mit zumeist schweren somatischen und sozialmedizinisch relevanten Folgeschäden [5]. Die frühzeitigere Inanspruchnahme professioneller Hilfen ist deshalb wichtig, wobei die Einflussgröße „Geschlecht“ als ein wesentlicher prädisponierender Faktor gelten kann [6]. In den letzten Jahren wird eine rege Diskussion über geschlechterspezifische Zuordnungen zu klinisch relevanten Subtypen bei Zwangserkrankungen geführt. Es lagen bis vor Kurzem keine publizierten Daten über einen geschlechterdifferenten Zusammenhang zwischen Beginn der Erkrankung, Inanspruchnahme von professioneller Hilfe und diagnostisch und prognostisch relevanten Verlaufsaspekten vor. In einer jüngst publizierten Studie zeigten sich sowohl hinsichtlich des Beginns der Erkrankung als auch bezüglich der Inanspruchnahme erster professioneller Hilfe Unterschiede zwischen weiblichen und männlichen Zwangserkrankten. Männer erkrankten tendenziell früher, nahmen später professionelle Hilfe in Anspruch und erhielten später eine diagnosespezifische Be-