Josef Marksteiner

Karl-Franzens-Universität Graz, Gratz, Styria, Austria

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Publications (197)557.99 Total impact

  • Zeitschrift für Neuropsychologie 06/2015; 26(2):131-142. DOI:10.1024/1016-264X/a000150 · 0.64 Impact Factor
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    ABSTRACT: Benzodiazepines (BZD) are frequently prescribed in patients with Alzheimer's disease (AD). Unfortunately, studies evaluating their benefits and risks in these patients are limited. Clinical trials focusing on the effect of BZD on cognitive functions, disease progression, behavioural symptoms, sleep disturbances and the general frequency of BZD use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioural and sleep disturbances). The frequency of BZD use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with BZD use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in AD-patients. No evidence was found for an improvement of sleep quality using BZD. This systematic review shows a relatively high prevalence of BZD use but limited evidence for clinical efficacy in AD patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 05/2015; DOI:10.1093/ijnp/pyv055 · 5.26 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a peripheral biomarker for AD. The aim of the present study was to functionally characterize platelets by FACS, to examine alterations in APP expression and secretion, and to measure serotonin levels in hypercholesterolemia mice with AD-like pathology and in two AD mouse models, the triple transgenic AD model (3xTg) and the APP overexpressing AD model with the Swedish-Dutch-Iowa mutations (APP_SweDI). These data are supplemented with epidermal growth factor (EGF) levels and compared with changes observed in platelets of patients with AD. We observed decreased platelet APP isoforms in 3xTg mice and patients with AD when analysed by means of Western blot. In patients, a significant increase of APP levels was observed when assessed by ELISA. Secreted APPβ proved to be altered amongst all three animal models of AD at different time points and in human patients with AD. Serotonin levels were only reduced in 7 and 14 month old 3xTg mice. Moreover, we found significantly lower EGF levels in human AD patients and could thereby reproduce previous findings. Taken together, our data confirm that platelets are dysfunctional in AD, however, results from AD animal models do not coincide in all aspects, and markedly differ when compared to AD patients. We support previous data that APP, as well as EGF, could become putative biomarkers for diagnosing AD in human platelets.
    Biogerontology 05/2015; 16(4). DOI:10.1007/s10522-015-9580-1 · 3.01 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions are seldom evaluated in AD. Recent investigations suggested that gender may be an important modifying factor in the development and progression of AD. We examined gender-specific differences in the pattern of cognitive dysfunction of patients with mild to moderate AD. We examined 113 males (mean age 78) and 173 females (mean age 80) of the prospective registry on dementia in Austria (PRODEM). We analyzed differences in the cognitive profile between male and female AD patients on the CERAD-Plus test battery. We found gender-related differences in the neuropsychological domains of verbal learning; the women tended to perform worse than men. Controlling for depression, stage and duration of dementia, and the level of education, there was still a significant effect of gender on verbal episodic memory. There is an interaction between gender and cognitive function, most notable in verbal episodic memory; female patients in the early stage of AD performed worse on verbal episodic memory than men. This indicates that the gender-specificities of neuropsychological functions should be given careful consideration in clinical diagnosis of dementia.
    Journal of Alzheimer's disease: JAD 04/2015; DOI:10.3233/JAD-150188 · 3.61 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular injury. The aim of the present study was to explore the presence and migration of platelets (thrombocytes) to sites of small vascular bleedings and/or to beta-amyloid plaques in the brain. We infused fluorescently labeled red PKH26 mouse platelets into transgenic Alzheimer mice overexpressing APP with Swedish/Dutch/ Iowa mutations (APP_SDI) and explored if platelets migrate into the brain. Further we studied whether platelets accumulate in the vicinity of ß-amyloid plaques. Our animal data shows that infused platelets are found in the liver and partly in the lung, while in the brain platelets were visible to a minor degree. In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels. In the brain of Alzheimer postmortem patients platelets could be detected by immunohistochemistry for CD41 and CD62P, but the majority was found in vessels with or without beta-amyloid load, and only a few single platelets migrated deeper into the brain. Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.
    Current Neurovascular Research 01/2015; 12(1). DOI:10.2174/1567202612666150102124703 · 2.74 Impact Factor
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    ABSTRACT: It is well established that L-type calcium channels (LTCC) are expressed in astroglia. However, their functional role is still speculative, especially under pathological conditions. We recently showed that the α1 subunit-like immunoreactivity of the CaV1.2 channel is strongly expressed in reactive astrocytes around beta-amyloid plaques in 11-month-old Alzheimer transgenic (tg) mice with the APP London and Swedish mutations (Daschil et al., 2013). The aim of the present study was to examine the cellular expression of all LTCC subunits around beta-amyloid plaques by situ hybridization using 35S labeled oligonucleotides. Our data show that mRNAs of the LTCC Cav1.2 α1 subunit as well as all auxiliary β and α2δ subunits, except α2δ-4, were expressed in the hippocampus of age-matched wt mice. It was unexpected to see, that cells directly located in the plaque core in the cortex expressed mRNAs for CaV1.2 α1, β2, β4 and α2δ-1, while no expression was detected in the halo. Further, cells in the plaque core also expressed preprotachykinin-A (PPT-A) mRNA, the precursor for substance P. By means of confocal microscopy we demonstrated that collagen-IV-stained brain vessels in the cortex were associated with the plaque core and were immunoreactive for substance P. In cortical organotypic brain slices of adult Alzheimer mice, we could demonstrate that LTCC blockers increased angiogenesis, which was further potentiated by substance P. In conclusion, our data show that brain vessels associated with beta-amyloid plaques express substance P and an L-type calcium channel and may play a role in angiogenesis.
    Neurobiology of Aging 12/2014; 304(3). DOI:10.1016/j.neurobiolaging.2014.12.027 · 4.85 Impact Factor
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    ABSTRACT: Einleitung: Es existieren nur wenige Untersuchungen, die explizit den Zusammenhang von elterlichen Verhaltensweisen in der Kindheit und zwanghafter Persönlichkeitsstörung untersuchen. Einige Studien konnten zeigen, dass die ausgeprägte Kontrolle der Eltern im Widerstreit mit den Autonomiebestrebungen des Kindes steht. Mittelpunkt dieser Untersuchung war es die Unterschiede der erinnerten Kindheitserfahrungen von PatientInnen mit einer zwanghaften Persönlichkeitsstörung und gesunder Personen mit Hilfe des SASB-Kurzform-Fragebogens zu erfassen. Methode: Aus den Daten der HELIOS Klinik Bad Grönenbach wurden die PatientInnen ausgewählt, die eine zwanghafte Persönlichkeitsstörung (N=84) als Diagnose hatten. Diesen wurde eine unabhängig erhobene Kontrollgruppe (N=79) ohne psychiatrische Diagnose gegenüber gestellt. Die erinnerten Eltern-Kind-Interaktionen wurden mit Hilfe des SASB Kurzform-Fragebogens erfasst, der Bindungsstil konnte über den RQ-2 Beziehungsstilfragebogen bestimmt werden. Ergebnisse: PatientInnen mit einer zwanghaften Persönlichkeitsstörung erinnerten sich an signifikant weniger Zuneigung in den Eltern-Kind-Interaktionen als die Kontrollgruppe. Sie nahmen die Mutter zudem als kontrollierender und übermäßig beschützender wahr. Die Gruppen unterschieden sich außerdem im herabsetzenden bzw. bestrafenden und vernachlässigenden Verhalten der Eltern. Die PatientInnen mit einer zwanghaften Persönlichkeitsstörung reagierten auf diese Verhaltensweisen mit sich abschotten und distanzieren. Zudem war die Störungsgruppe signifikant unsicherer gebunden als die Kontrollgruppe und wies eine signifikant negativere Selbst- und Fremdrepräsentanz als gesunde Personen auf. Zusammenfassend ist erkennbar, dass sich die Kindheitserfahrungen von Personen mit einer zwanghaften Persönlichkeitsstörung von denen gesunder ProbandInnen unterscheiden. Besonders das kontrollierende und wenig liebevolle Verhalten der Mutter scheint ein Aspekt der multifaktoriellen Genese einer zwanghaften Persönlichkeitsstörung sein. In weiteren Untersuchungen müsste erforscht werden, inwieweit die entdeckten Eltern-Kind-Interaktionen und Bindungsstile für das Störungsbild charakteristisch sind.
    DPGGN Kongress Berlin; 11/2014
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    ABSTRACT: Einleitung: Patienten im akuten Alkoholentzug weisen neben einer Reihe an vegetativen Symptomen häufig psychische Beeinträchtigungen und eine Veränderung des Stresshormons Cortisol auf. Ziel dieser Pilotstudie war es den Verlauf der vorhandenen psychischen und körperlichen Beeinträchtigungen im Alkoholentzug zu erfassen. Die Lichttherapie wurde als therapieunterstützende Intervention eingesetzt. Methode: 30 stationäre Patienten im akuten Alkoholentzug wurden randomisiert der Teilnahme an der Lichttherapie bzw. der Kontrollbedingung zugeordnet. Vor und nach einer fünftägigen täglichen Anwendung der Lichttherapie wurden der Cortisolspiegel im Speichel (Cortisol-Awakening-Response CAR), die Entzugssymptomatik (CIWA) sowie psychometrische Variablen (BDI, STAI) quantifiziert. Ergebnisse: Im Verlauf des Alkoholentzugs verbesserte sich sowohl körperliche als auch psychische Symptomatik signifikant. Es zeigte sich außerdem eine signifikante Korrelation zwischen der Höhe des morgendlichen Cortisolspiegels vor und der Schwere der Entzugserscheinung nach Abschluss der Lichttherapie. Diese Veränderungen erwiesen sich als unabhängig von der Teilnahme an der Lichttherapie. Zusammenfassend wurde in dieser Studie der morgendliche Cortisolwert zu Beginn der Intervention als prädiktiver Parameter für die Schwere der Alkoholentzugssymptomatik nach Abschluss der Lichttherapie identifiziert. Es zeigte sich, dass vor allem ein niedrigerer Ausgangscortisolwert zu einer schnelleren Remission der Alkohlentzugssymptomatik beiträgt.
    DPGGN Kongress Berlin; 11/2014
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    ABSTRACT: Einleitung: Patienten im akuten Alkoholentzug weisen neben einer Reihe an Beeinträchtigungen auch eine Störung ihrer zirkadianen Rhythmik auf. Aus Grundlagenstudien ist hinlänglich bekannt, dass die Lichttherapie diese positiv beeinflussen bzw. normalisieren kann. Durch die Erfassung der motorischen Aktivität, unter Berücksichtigung des Schlaf-/Wachrhythmus kann das Ausmaß des Regulierungseffektes der Lichttherapie eingeschätzt werden. Ziel dieser Pilotstudie war es demnach, den Einfluss der Lichttherapie auf die motorische Aktivität im Alkoholentzug zu erfassen. Methode 23 stationäre Patienten im akuten Alkoholentzug wurden randomisiert der Teilnahme an der Lichttherapie bzw. der Kontrollbedingung zugeordnet. Die Studienteilnahme umfasste 11 Tage. An fünf aufeinander folgenden Tagen innerhalb dieses Zeitraums kam die Lichttherapie zur Anwendung. Während des gesamten Zeitraums wurde die motorische Aktivität mittels eines Aktigraphen erfasst. Ergebnisse In beiden Gruppen zeigte sich im gesamten Zeitraum des akuten Alkoholentzugs eine deutliche Steigerung der motorischen Aktivität. Im direkten Gruppenvergleich zeigten sich nach Abschluss der LT signifikante Unterschiede im tageszeitabhängigen Verlauf. Die Experimentalgruppe wies eine signifikante Steigerung der motorischen Aktivität am späten Nachmittag sowie eine signifikant niedrigere motorische Aktivität in der zweiten Nachthälfte auf. Zusammenfassend konnte nach Abschluss der Intervention eine positive Wirkung der Lichttherapie festgestellt werden. Die Lichttherapie trägt maßgeblich zur Regulation der motorischen Aktivität bei. Durch die lichttherapievermittelte Verstärkung des natürlichen Schlaf-/Wachrhythmus profitieren Patienten im Alkoholentzug von dieser Intervention.
    DGPPN Kongress Berlin; 11/2014
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    ABSTRACT: To record and measure the nature and severity of stigma and discrimination experienced by people during a first episode of schizophrenia and those with a first episode of major depressive disorder.
    International Journal of Social Psychiatry 10/2014; DOI:10.1177/0020764014551941 · 1.15 Impact Factor
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    ABSTRACT: Background: Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15-20% of conversion to Alzheimer's disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD. Objective: In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population. Method: Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM. Results: At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results. Conclusion: Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.
    PLoS ONE 08/2014; 9(8):e106062. DOI:10.1371/journal.pone.0106062 · 3.53 Impact Factor
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    ABSTRACT: Background: Patient dependence has rarely been studied in mild-to-moderate Alzheimer's disease (AD). Objective: To identify factors which predict patient dependence in mild-to-moderate AD. Methods: We studied 398 non-institutionalized AD patients (234 females) of the ongoing Prospective Registry on Dementia (PRODEM) in Austria. The Dependence Scale (DS) was used to assess patient dependence. Patient assessment comprised functional abilities, neuropsychiatric symptoms and cognitive functions. A multiple linear regression analysis was performed to identify predictors of patient dependence. Results: AD patients were mildly-to-moderately impaired (mean scores and SDs were: CDR 0.84 ± 0.43; DAD 74.4 ± 23.3, MMSE = 22.5 ± 3.6). Psychopathology and caregiver burden were in the low range (mean NPI score 13.2, range 0 to 98; mean ZBI score 18, range 0-64). Seventy five percent of patients were classified as having a mild level of patient dependence (DS sum score 0 to 6). Patient dependence correlated significantly and positively with age, functional measures, psychopathology and depression, disease duration, and caregiver burden. Significant negative, but low correlations were found between patient dependence, cognitive variables, and global cognition. Activities of daily living, patient age, and disease severity accounted for 63% of variance in patient dependence, whereas cognitive variables accounted for only 11%. Conclusion: Dependence in this cohort was mainly related to age and functional impairment, and less so to cognitive and neuropsychiatric variables. This differs from studies investigating patients in more advanced disease stages which found abnormal behavior and impairments of cognition as main predictors of patient dependence.
    Journal of Alzheimer's disease: JAD 08/2014; DOI:10.3233/JAD-140099 · 3.61 Impact Factor
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    ABSTRACT: Background: In Western cultures it has often been assumed that the experience of happy or sad emotions while listening to music is clearly correlated to the key (mode) and the tempo of the musical piece. Recent studies point towards more complex dependencies, but knowledge in this line of research is still very limited, especially regarding the experience of music for persons with memory-related disorders such as dementia. Objective: This pilot study explores the emotional content of music for patients with mild cognitive impairment (MCI) and early-stage Alzheimer's disease (AD) and compares them to healthy subjects. Methods: A new test was specifically designed for this study and presented to 10 patients with MCI diagnosis, 10 with AD diagnosis and 23 controls. The test comprised musical stimuli consisting of chords and short musical pieces in major and minor mode with variable note density (number of notes per second). Results: In the current study no significant correlation between key and the attribution of 'happy' or 'sad' judgements to a musical piece could be found in all groups. Note density, however, was shown to exhibit a strong influence on happy/sad judgements in all groups. Conclusion: Our findings indicate that the note density of a musical piece is much more important for happy/sad judgements than the key. Furthermore, the diagnosis MCI and early AD had no influence on the attribution of emotional expressions to musical pieces, corroborating recent findings of spared memory for music in these patient groups. © 2014 S. Karger AG, Basel.
    Gerontology 05/2014; 60(5). DOI:10.1159/000358010 · 2.68 Impact Factor
  • Peter Mikosch, Josef Marksteiner
    Wiener Medizinische Wochenschrift 01/2014; 164(1-2). DOI:10.1007/s10354-013-0257-6
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    ABSTRACT: Background/Aims: This study aimed to investigate whether the serial position effects in memory can differentiate patients with different subtypes of mild cognitive impairment (MCI) from healthy controls and patients with different stages of Alzheimer's disease (AD). Methods: The serial position effects was tested with the CERAD word list task in 184 persons (39 healthy control subjects, 15 amnestic MCI single domain subjects, 23 amnestic MCI multiple domain subjects, 31 nonamnestic MCI subjects, 45 early or mild AD patients, and 31 moderate AD patients). Results: With progression of dementia, memory deficits increased and the impairment in the primacy effect during the learning trials advanced, whereas the recall of recent items was less impaired. The serial position profile of nonamnestic MCI patients resembled that of healthy control subjects, whereas amnestic MCI patients showed poorer performance in all 3 positions but no significant difference as a function of serial word position. Conclusion: Analyses of the serial position effect may be a useful complement to clinical neuropsychological measures for distinguishing amnestic MCI patients from normal aging and patients with different stages of dementia. © 2013 S. Karger AG, Basel.
    Dementia and Geriatric Cognitive Disorders 01/2014; 37(1-2):19-26. DOI:10.1159/000351675 · 2.81 Impact Factor
  • European Psychiatry 01/2014; 29:1. DOI:10.1016/S0924-9338(14)77927-1 · 3.21 Impact Factor
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    ABSTRACT: Alkoholkonsum kann zu einer akuten Intoxikation mit entsprechender klinischer Symptomatik führen. Im ersten Stadium der Alkoholintoxikation kommt es zur Exzitation mit Enthemmungen, verlängerten Reaktionszeiten und verminderter Schmerzwahrnehmung, sowie zu nachweisbaren Veränderungen der kognitiven Leistungen insbesondere zu einer Beeinträchtigung der Gedächtnisleistungen. Jedoch sind die kognitiven Folgen einer Intoxikation in den allermeisten Fällen reversibel sofern keine Alkoholabhängigkeit besteht. Durch chronischen Alkoholkonsum ergeben sich erhebliche neuropsychologische Defizite. Insbesondere zeigen Alkoholkranke eine deutliche Dysfunktionalität in der sozialen Kognition sowie Defizite in exekutiven Funktionen wie in Problemlösefähigkeiten und Abstraktion, beim Entscheidungstreffen, Planen und Organisieren aber auch Beeinträchtigung der Handlungskontrolle und Inhibierung. Bei etwa 50 % der Alkoholabhängigen sind Einbußen der Kognition mit einer zerebralen Atrophie in der Bildgebung des Gehirns vergesellschaftet. Es zeigen sich auch geschlechtsspezifische Unterschiede, sowohl auf akute Alkoholintoxikation, als auch bei chronischem Alkoholkonsum reagieren Frauen vulnerabler mit Entwicklung dauerhafter Schäden.
    Wiener Medizinische Wochenschrift 01/2014; 164(1-2). DOI:10.1007/s10354-013-0226-0
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    ABSTRACT: Alzheimer´s disease (AD) is a severe neurodegenerative disease. Cerebrovascular changes often accompany AD-related pathology. Despite a considerable progress in the diagnostic accuracy of AD, no blood biomarkers have been established so far. The aim of the present study was to search for changes in plasma levels of 27 vascular-related proteins of healthy controls, patients with mild cognitive impairment (MCI) and AD. In a sample of 80 participants we showed that out of these 27 proteins, eight proteins were slightly changed (up to 1.5x) in AD (alpha2-macroglobulin, apolipoprotein-A1, plasminogen activator inhibitor, RAGE, Tissue Inhibitors of Metalloproteinases -1 and Trombospondin -2), one marker (serum amyloid A) was enhanced up to 6x but with a very high variance. However, N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced both in MCI and AD patients (1.9x). In a second analysis of a sample of 110 subjects including younger healthy controls, we confirmed that NT-proBNP has the potential to be a stable candidate protein for both diagnosis and AD disease progression.
    Experimental gerontology 12/2013; 50. DOI:10.1016/j.exger.2013.12.001 · 3.53 Impact Factor
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    ABSTRACT: In Austria, geriatric psychiatry is referred to as geriatric psychiatry or psychiatry of old age. It is recognized as a subspecialty of psychiatry focusing on the study, prevention, and treatment of mental disorders in humans with old age. The age limits vary between 60 and 65 years. In this review, we report the current status of geriatric psychiatry based on data sources published by government agencies or public health bodies, as well as telephone surveys of respective institutions or specific questionnaires. Overall, in Austria there is only one department for geriatric psychiatry. Several psychogeriatric units are located in Departments of Psychiatry. So far, no board certification has been established for geriatric psychiatry. An education on geriatrics for physicians in internal medicine, neurology, physical medicine and general rehabilitation or psychiatrist also includes courses for geriatric psychiatry. Patients suffering from various types of dementia constitute the largest group of psychogeriatric patients. Patients with dementia, however, are also treated by neurologists or general practitioners. To further promote education, medical trainings or research in the field of geriatric psychiatric, Austria should strive for close European co-operations, especially with countries with a comparable health system.
    12/2013; DOI:10.1016/j.gmhc.2013.10.001

Publication Stats

4k Citations
557.99 Total Impact Points

Institutions

  • 2010–2014
    • Karl-Franzens-Universität Graz
      • • Section for Biological Psychology
      • • Institute of Psychology
      Gratz, Styria, Austria
  • 1988–2014
    • University of Innsbruck
      • • Institut für Psychologie
      • • Institute of Biochemistry
      • • Department of Pharmacology
      Innsbruck, Tyrol, Austria
  • 2013
    • Windsor Regional Hospital
      Windsor, Ontario, Canada
  • 2009–2013
    • Medizinische Universität Innsbruck
      • Department of Psychiatry and Psychotherapy
      Innsbruck, Tyrol, Austria
  • 2007
    • University of Salzburg
      Salzburg, Salzburg, Austria