TY - JOUR A1 - Kingslake, Jonathan A1 - Dias, Rebecca A1 - Dawson, Gerard R. A1 - Simon, Judit A1 - Goodwin, Guy M. A1 - Harmer, Catherine J. A1 - Morriss, Richard A1 - Brown, Susan A1 - Guo, Boliang A1 - Dourish, Colin T. A1 - Ruhé, Henricus G. A1 - Lever, Anne G. A1 - Veltman, Dick J. A1 - van Schaik, Anneke A1 - Deckert, Jürgen A1 - Reif, Andreas A1 - Stäblein, Michael A1 - Menke, Andreas A1 - Gorwood, Philip A1 - Voegeli, Géraldine A1 - Perez, Victor A1 - Browning, Michael T1 - The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial JF - Trials N2 - Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depressionmeasured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. KW - psychiatry KW - depression KW - prediction KW - treatment KW - antidepressant KW - primary care Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173012 VL - 18 ER - TY - THES A1 - Langer, Simon T1 - Herz-Hirn Interaktion im Mausmodell: Herzinsuffizienz nach Myokardinfarkt führt zu depressivem Verhalten bei Mäusen T1 - Heart & Brain interactions in mice: chronic heart failure after myocardial infarction leads to depressive behaviour in mice N2 - Herzinsuffizienz, Depression und Angststörungen treten gehäuft gemeinsam auf und beeinflussen teilweise gegenseitig ihre Prognose. Die Zusammenhänge zwischen diesen Erkrankungen sind bislang nicht aufgeklärt. In der vorliegenden Arbeit führte ischämische Herzinsuffizienz im Mausmodell zu Depressions-ähnlichem Verhalten innerhalb von 8 Wochen nach Infarktinduktion. Weiter zeigte sich eine Minderung der Gedächtnisleistung. Angst-assoziiertes Verhalten ließ sich nicht nachweisen. Immunhistochemisch konnten keine Veränderungen in spezifischen Hirnarealen nachgewiesen werden. Molekulare Methoden legen Veränderungen des Serotoninstoffwechsels als mögliche Erklärung nahe. Nach operativer Ligatur eines Herzkrankgefäßes wurden C57/Bl6N Mäuse über einen Zeitraum von 8 Wochen beobachtet. In dieser Zeit wurden neben Herzultraschalluntersuchungen eine Reihe von Verhaltenstest durchgeführt, um depressive und ängstliche Verhaltensstrukturen sowie die kognitive Leistungsfähigkeit beurteilen zu können. Nach Ablauf des Beobachtungszeitraumes wurden das Herz und das Gehirn entnommen und weiteren histologischen und molekularen Untersuchungen zugeführt. Die histologische Aufarbeitung des Herzens nach Ende des Versuchszeitraumes bestätigte die Beobachtungen anderen Autoren, dass eine Infarktgröße von mehr als 30% mit sehr hoher Wahrscheinlichkeit zur Entstehung einer Herzinsuffizienz führt. Im der histologischen Aufarbeitung des Gehirns zeigen sich keine strukturellen Veränderungen bei herzkranken Mäusen, die die beobachteten Änderungen im Verhalten begründen könnten. Insbesondere kann eine hypoxische Hirnschädigung durch eine etwaige Minderperfusion empfindlicher Hirnareale ausgeschlossen werden. Mäuse, die nach Induktion eines Myokardinfarktes eine Herzinsuffizienz entwickeln, zeigen nach 8 Wochen Depressions-assoziiertes, adynamisches Verhalten sowie eine Verminderung der kognitiven Leistungsfähigkeit, nicht aber Anzeichen von Angststörungen. Diesen Verhaltensänderungen kann kein strukturelles Korrelat im Gehirn zugewiesen werden. Dies ist ein Indiz dafür, dass sich Veränderung auf molekularer Ebene vollziehen, welche sich dem Mikroskop entziehen. Die im Myokard beobachtete Regulation des Serotoninstoffwechsels ist ein möglicher Erklärungsansatz hierfür. N2 - Chronic heart failure and depression are common comorbidities, that also have influence on the overall prognosis. The pathomechanisms of these illnesses remain still to be uncovered. In this experiment, we investigated mice with chronic heart failure after myocardial infarction over a period of 8 weeks. Male C57/Bl6N mice underwent ligation of the left anterior descending coronary artery. Heart failure was both confirmed by echocardiography and post-mortem. Sham-operated mice without ligation were used as control group. We discovered that these mice developed behavioral signs of depression in multiple behavioral testing. Also, we found signs for cognitive impairment in the object recognition task. No signs of increased anxiety was found. The hippocampal brain region is associated with the genesis of behaviour. Immunohistochemistry of the brain showed no morphological changes in this distinct area. We found increased expression of genes connected to the serotonine pathway in mice suffering from chronic heart failure, suggesting a possible pathomechanism for the shown behavioral changes. KW - Deutsches Zentrum für Herzinsuffizienz Würzburg KW - Herzinsuffizienz KW - Depression KW - Herzinsuffizienz KW - Depression KW - Verhalten KW - heart failure KW - behavioral changes KW - depression KW - C57/Bl6 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154733 ER - TY - JOUR A1 - Hofmann, Lukas A1 - Karl, Franziska A1 - Sommer, Claudia A1 - Üçeyler, Nurcan T1 - Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease JF - PLoS ONE N2 - Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. KW - cognitive impairment KW - mouse models KW - depression KW - swimming KW - learning KW - Fabry disease KW - genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170745 VL - 12 IS - 6 ER -