Patient-reported outcomes are important in nonalcoholic fatty liver disease (NAFLD). Pruritus is of special interest for evolving therapies with farnesoid X receptor (FXR) agonists. The aim of this study was to investigate the prevalence of pruritus in a real-life NAFLD cohort and analyze associations with anxiety and depression. Pruritus was assessed using a visual analogue- (VAS) and 5-D itch-scale (5-D). Anxiety and depression were evaluated by Beck’s-Depression-Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS-A, HADS-D). An optimal logistic regression model was found with a stepwise procedure to investigate variables associated with pruritus. In total, 123 NAFLD patients were recruited. VAS and 5-D were highly correlated (Spearman’s correlation coefficient 0.89). Moderate/severe pruritus was reported in 19% (VAS) and 21% (5-D) of patients. Anxiety and depression were present in 12% and 4% (HADS-A and HADS-D, respectively) and 12% (BDI) of cases. There was a significant association between VAS and BDI (p = 0.019). The final multivariate model for 5-D included diabetes mellitus (OR 4.51; p = 0.01), BDI (OR 5.98; p = 0.024), and HADS-A (OR 7.75; p = 0.011). One-fifth of NAFLD patients reported moderate or severe pruritus. 5-D was significantly associated with diabetes mellitus, depression, and anxiety. These findings should be tested in larger populations and considered in candidates for treatment with FXR agonists.

Background and objectives: Despite a generally good prognosis, testicular cancer can be a life-altering event. We explored perceived positive and negative life changes after testicular cancer in terms of frequency, demographic and disease-related predictors, and associations with depression and anxiety. Materials and methods: All testicular cancer survivors receiving follow-up care at two specialized outpatient treatment facilities were approached at follow-up visits or via mail. We assessed a total of N = 164 patients (66% participation rate, mean time since diagnosis: 11.6 years, SD = 7.4) by the Posttraumatic Growth Inventory (PTGI, modified version assessing positive and negative changes for each of 21 items), Patient-Health-Questionnaire-9 (PHQ-9), and Generalized-Anxiety- Disorder-Scale-7 (GAD-7). We conducted controlled multivariate regression analyses. Results: Most survivors (87%) reported at least one positive change (mean number: 7.2, SD = 5.0, possible range: 0–21). The most frequent perceived positive changes were greater appreciation of life (62%), changed priorities in life (62%), and ability rely on others (51%). At least one negative change was perceived by 33% (mean number of changes: 1.1, SD = 2.5). Negative changes were most frequent for decreases in self-reliance (14%), personal strength (11%), and ability to express emotions (9%). A higher socioeconomic status was associated with more positive changes ( = 0.25, 95% CI 0.08 to 0.42); no other association with demographic and disease-related predictors emerged. While positive life changes were not associated with depression ( = 0.05, 95% CI 0.17 to 0.07) and anxiety ( = 0.00, 95% CI 0.13 to 0.13), more negative life changes were significantly associated with higher depression ( = 0.15, 95% CI 0.03 to 0.27) and anxiety ( = 0.23, 95% CI 0.11 to 0.36). There was no significant interaction of positive and negative changes on depression or anxiety. Conclusions: Although positive life changes after testicular cancer are common, a significant number of survivors perceive negative changes in life domains that have been primarily investigated in terms of personal growth. Early identification of and psychosocial support for patients who perceive predominantly negative changes may contribute to prevention of prolonged symptoms of anxiety and depression.

Hintergrund: Schwindel ist ein häufig vorgetragenes Symptom beim Hausarzt. Seine erhöhte Vergesellschaftung mit Ängstlichkeit und Depressivität ist aber bisher zu wenig untersucht worden, ebenso wenig ist dieser Zusammenhang Gegenstand der hausärztlichen Behandlung von Schwindelpatienten. Zielstellung: Kommen unbekannte psychische Hintergründe in Kombination mit Schwindel im hausärztlichen Patientengut häufiger vor als ohne Schwindel? Ergeben sich daraus als Konsequenz unterschiedliche Versorgungsformen durch den Hausarzt? Wie verhält es sich mit deren subjektiven Gesundheitszustand, dem Erfolg der hausärztlichen Behandlung, dem ihnen entgegengebrachten Verständnis und der Häufigkeit der Arztbesuche der Betroffenen? Studiendesign: Prospektive Multicenterstudie in der Allgemeinpraxis Untersuchungsregion: Zehn Hausarztpraxen in Halle a.d. Saale und Nordsachsen/ Leipzig im städtischen und ländlichen Einzugsbereich, welche von Fachärzten für Allgemeinmedizin geführt wurden. Methodik: Die Studie untersuchte insgesamt 590 zufällig am Untersuchungstag eintreffende Patienten in jeweils einer von insgesamt zehn Hausarztpraxen. Die Ausprägung von Schwindelbeschwerden und eventuell vorhandene Merkmale von Ängstlichkeit und Depressivität beim jeweiligen Patienten wurden mit Elementen des Gießener Beschwerdebogens 24 und der Hospital Anxiety and Depression Scale (deutsche Version) untersucht. Ergebnisse: Die Patienten wurden in eine Gruppe mit relevanten (29,7%, n=175) und in eine Gruppe ohne relevante Schwindelbeschwerden (70,3%, n=408) eingeteilt (Cut off >=8 nach GBB 24). Die Gruppe mit relevantem Schwindel wies häufiger Merkmale für Ängstlichkeit (p<0,001) und Depressivität (p<0,001) in allen Altersgruppen auf, zeigte sich unzufriedener mit ihrem Behandlungserfolg (p=0,004), schätzte ihren aktuellen Gesundheitszustand schlechter ein (p<0,001) und konsultierte ihren Hausarzt in den letzten zwölf Monaten häufiger (p=0,020). Sie stellten sich nach ICPC-2 häufiger wegen neurologischer (p<0,001), psychologischer (p=0,026) und unspezifischer Beschwerden (p<0,001) vor. Sie erhielten mehr Diagnosen aus den ICD-10-Kapitel V (Psychische und Verhaltensstörungen) (p=0,030). Diese Patienten waren nach HADS-D auch häufiger psychisch auffällig (p<0,001). Relevanter Schwindel kam bei Frauen aller Altersgruppen häufiger vor als bei Männern (p<0,001). Dennoch ergaben sich keine Behandlungsunterschiede durch die Hausärzte zwischen beiden Gruppen (p=0,101 bis 0,930 je nach ärztlicher Maßnahme). Schlussfolgerung: Schwindelpatienten weisen häufger Ängstlichkeit und Depressivität auf, welche den Schwindel unterhalten. Dieser Zusammenhang sollte in der Sprechstunde bedacht werden. Die psychischen Hintergründe sollten vom Hausarzt aufgedeckt und behandelt werden. Dadurch könnte der Schwindel und damit der subjektive Gesundheitszustand der betroffenen Patienten verbessert und die Inanspruchnahme des Gesundheitswesens verringert werden.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Lucie Ambrožová Supervisor: Doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: Intestinal microbiota and mood disorders The intestinal microbiom is composed mainly of two dominated strains - Bacteroidetes and Firmicutes. The other strains are just not numerous like the previous ones. The specimens have the invariable core of microbiom which doesn't change in time. Nevertheless they have also the transient gut bacteria, which change during their life. Intestinal microbiom is influenced by many factors. Between them we can categorize for example the way of the childbirth, the breast - feeding, the alimentation, the state of health, and the medicaments. Every specimen has own specific microbiom. It was found that human population is possible to divide into three intestinal groups or enterotypes. To each enterotype dominates different bacterial strain. It was proved that intestinal microbiom communicates with the brain and it works also vice versa. This communication system is called "brain - intestine" and takes several ways in several body systems (such as nervous, endocrine, metabolic, and immune). To normal development of the brain is needed the right colonisation of non...

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2006. / Title from title page screen (viewed on October 26, 2007 ). Research advisor: Mona Newsome Wicks, Ph.D., RN. Document formatted into pages (xii, 174 p. : ill.) Vita. Abstract. Includes bibliographical references (p. 115-132).

Background: Cardiac Rehabilitation (CR) has been shown to be effective in reducing mortality and morbidity in Coronary Heart Disease (CHD). There is a limited amount of research that evaluates the impact of menu-based CR, in patients with Acute Coronary Syndrome with Low Troponin levels (ACSLT). Aim: This thesis contains a feasibility study and an exploratory study. The feasibility study aimed to examine the feasibility of a Randomised Controlled Trial (RCT) which would test the impact of a menu-based CR programme, on individuals diagnosed with ACSLT, against standard care. This feasibility study included staff views. The exploratory study aimed to explore the impact that ACSLT and CR can have on this client group. Method: The feasibility study was a repeated measures case-control trial of menu-based CR based on the theoretical framework of the Common Sense Model of Self-Regulation (CSM), using a range of health assessments. The areas assessed included misconceptions, symptoms, anxiety, depression and Health Related Quality of Life (HRQoL). In addition, focus groups were held with both ward and specialist CR staff to seek their views on the feasibility of a RCT of menu-based CR for ACSLT. The exploratory study consisted of description and analysis of the data that had been collected from the participants over the two year period as above. In addition it included qualitative data that had been collected during interviews with the participants. Findings: Participants (n=33) were recruited from cardiology wards following an admission with ACSLT. They were assessed at baseline (T1), nine months (T3) and 24 months (T4). Twenty-five participants completed the studies. The feasibility study was successful in its aim of testing the CR intervention and protocols for a further RCT. The intervention was acceptable to the participants and to the specialist staff, although the ward staff did not see the need for a RCT. The measures used, with the exception of the self-reporting measures, were suitable and provided a wide range of data that could be utilised in a RCT. However the changes to diagnostic categories meant that a RCT would no longer be feasible. The exploratory study found that both groups were similar on a range of baseline demographic and clinical factors. There was a tendency to benefit within the exploratory study which favoured the intervention. An additional finding from the exploratory study was the degree of uncertainty experienced by the participants, within the context of a changing political and clinical landscape. Discussion and conclusions: The studies presented in this thesis add to our knowledge by highlighting some of the difficulties in designing a RCT of menu-based CR in a specific subgroup of CHD and by presenting outcome data for a small group of participants that have not previously been studied within the literature. This data suggests that there was a tendency to benefit for the intervention that requires further study. Implications for practice: Patients with ACSLT are now being included in CR programmes due to the changes within the diagnostic criteria. Clinicians have little understanding of the impact of CR on this group of patients, or what type of interventions would work best. Large RCT’s will however be problematic and this thesis has highlighted that further work is required to explore how CR can best improve the well-being of individuals with ACSLT.

Environ 30% des patients ne répondent pas de manière adéquate à un traitement antidépresseur. Cette absence de rémission, voire aggravation de l’état dépressif après la mise en place du traitement est qualifiée de non-réponse au traitement. La résistance au traitement est caractérisée lorsque cet échec thérapeutique est récurrent pour différentes stratégies thérapeutiques de mécanisme d’action différents. Afin d’améliorer les stratégies thérapeutiques visant à traiter les patients résistants, une meilleure compréhension des mécanismes biologiques associés à la non-réponse/résistance est nécessaire. De nombreux travaux ont associé le phénomène de neurogenèse hippocampique adulte à la réponse antidépressive, et ont montré qu’un blocage de la neurogenèse altère la réponse antidépressive chez la Souris. Cependant, aucune étude n’a montré si la non-réponse/résistance au traitement était associée à des altérations de la neurogenèse. De plus, il n’existe à ce jour aucun modèle de résistance qui ne présente une validité translationelle à ce qui est observé chez l’Homme. Enfin, alors que 2/3 des patients dépressifs sont des femmes, la majorité des études précliniques sont réalisées chez des mâles. Le but de mon travail de thèse a donc été de modéliser la résistance au traitement antidépresseur chez la souris C57BL6 mâle et femelle.Le premier objectif de ce travail a été la modélisation chez la femelle d’un phénotype anxio-dépressif, en adaptant un modèle neuroendocrinien de la dépression élaboré chez le mâle, basée sur l’administration chronique de corticostérone. Le deuxième objectif a été l’étude de la comparaison de la neurogenèse entre les souris répondeuses et non-répondeuses à un traitement chronique de fluoxétine ou résistantes à 2 stratégies successives de traitement présentant un mécanisme d’action différent (fluoxétine puis imipramine).D’autre part, les données de la littérature clinique suggèrent qu’un marqueur périphérique, la protéine β-arrestine 1, serait un marqueur de l’état dépressif et de la réponse au traitement. Nous avons donc mesuré dans notre modèle les variations de ce potentiel biomarqueur clinique.L’ensemble de ces travaux de thèse a permis de montrer la complexité d’induire un phénotype anxio/dépressif chez la souris femelle de façon stable et robuste via l’administration chronique de corticostérone. Chez le mâle, nous avons pu modéliser la résistance au traitement antidépresseur dans le modèle CORT. Nous avons pu observer que les processus neurogéniques semblent jouer un rôle essentiel dans la réponse au traitement, puisqu’une absence de réponse est associée avec une altération de la neurogenèse hippocampique adulte. Si dans notre modèle, l’expression périphérique de la β-arrestine 1 n’est pas diminuée chez les souris présentant un phénotype anxio-dépressif, elle permet cependant de discriminer les souris répondeuses des souris résistantes au traitement, ce qui valide son intérêt en tant que biomarqueur de la réponse antidépressive. / Around 30% of patients do not respond adequately to chronic antidepressant treatments. This lack of response, or worsening of the depressive state after the onset of the treatment can lead to treatment resistant depression (TRD). TRD is characterized by a recurrent lack of therapeutic response to various antidepressant which display different mechanism of action. A better understanding of the mechanisms that underlies TRD is necessary to discover some new effective therapeutic strategies. Numerous studies in rodents have shown that chronic antidepressant treatment improves adult hippocampal neurogenesis, and that disrupting this phenomenon partially alters antidepressant response. However whether lack of response or resistance to antidepressant treatment is associated with altered neurogenesis has yet not been observed. Additionally, there is yet no model of TRD with a translational validity. As major depressive disorders affects women twice more than men, yet the preclinical studies are performed mostly in males. Thus, the aim of this thesis was to model non-response an resistance to antidepressant response in male and female C57BL6 mice.The first aim of this thesis work was to induce a anxio-depressive phenotype in female mice, by adapting a neurodencocrine model of depression developed in males and based on chronic administration of corticosterone (CORT). The second aim was to study adult hippocampal neurogenesis in animals that respond or not to chronic fluoxetine administration, and in animals that were resistant to two successive antidepressant treatment with a different mechanism of action (fluoxetine and then imipramine).Additionally, data from the literature suggests that peripheral β-arrestin 1 expression could be a potential biomarker of depressive state and antidepressant response in humans. Thus, we explore its validity in our model of TRD in mice.Overall, our results highlight the difficulty of inducing an anxio-depressive phenotype in female mice, using different dosage or treatment duration of corticosterone, which hampers the use of corticosterone to induce emotionality in female mice.However, in male mice, we showed that we were able model resistance to treatment in the using the CORT model. Lack of response to chronic fluoxetine and treatment resistance to fluoxetine/imipramine were associated with altered neurogenesis in the dentate gyrus of the hippocampus. This confirms that hippocampal neurogenesis is critical for a full antidepressant response. While peripheral β-arrestin 1 expression was not decreased after chronic CORT exposure, its differential expression between responder vs treatment-resistant mice confirms its validity as a biomarker for antidepressant response.

Background: Recalled parental rearing behavior is one of the factors influencing the strength of resilience. However, it is unclear whether resilience is a relatively stable personality trait or has a relational character whose protective strength changes over the course of life. Therefore, the association between recalled parental rearing and resilience as well as symptoms of anxiety and depression was investigated in respect to age and gender. Methods: N = 4,782 healthy subjects aged 14-92 (M = 48.1 years) were selected by the random-route sampling method. In this sample, an ultra-short form of the Recalled Parental Rearing Behavior Questionnaire, the German short version of the resilience scale, and two screening instruments for depression and anxiety (PHQ-2, GAD-2) were filled out. Structural equation modelling was used to analyze the data estimated with the maximum likelihood method approach. Results: The data revealed that rejection and punishment were clearly associated with lower resilience. Moreover, resilience had a strong connection to the symptoms of anxiety and depression. Resilience had the same quality of association in both men and women with respect to anxiety and depression. Furthermore, the effect of resilience did not vary across several age groups even though challenges may differ over a lifetime. Conclusion: Recalled parental rearing behavior such as rejection and punishment as well as control and overprotection exert a significant association on the strength of resilience. Resilience has an effect independent of gender and does not affect people of different age groups differently.

Background: Whereas the role of externalizing disorders is relatively well established in predicting the onset of cannabis use (CU) or cannabis use disorder (CUD), the status of anxiety and mood disorders in predicting CU and CUD remains controversial. Objective: (1) To examine cross-sectional and prospective associations of CU and CUD with a range of mental disorders and whether anxiety and mood disorders are associated with CU/CUD after adjusting for externalizing disorders. Methods: N = 1395 community subjects aged 14–17 at baseline were followed-up at three waves prospectively over 10 years. Substance use, substance disorders and mental disorders were assessed using the DSM-IV/M-CIDI. Results: (1) The baseline prevalence rates where 19.3% at t0 for CU and 2.6% for CUD. Cumulative incidence rates at t3 were 54.3% for CU and 13.7% for CUD. (2) In cross-sectional and prospective analyses other substance use disorders, mood and anxiety disorders were associated with CU and CUD. (3) Associations of panic-anxiety with CU and of depressive and bipolar disorders with CU and CUD were significant after controlling for externalizing disorders. Conclusion: A range of psychopathological conditions, including depressive, bipolar and less consistently anxiety disorders as well as the degree of their comorbidity are significantly associated with incident CU and progression to CUD, even when controlling for externalising disorders. A better understanding of this complex interplay may result in better aetiological models and intervention strategies.

Im Rahmen einer Reanalyse von vier Erhebungen an jugendlichen und erwachsenen Probanden in den neuen und alten Bundesländern in den Jahren 1990 bis 1991/92 wurden Angaben zu Indikatoren für Depressivität, Angst/psychosomatische Beschwerden und Substanzgebrauch in Ost- und Westdeutschland verglichen. Zum Zeitpunkt der Untersuchungen gab es im Gegensatz zu der von einzelnen Autoren angeführten Erwartung keine eindeutigen Hinweise auf eine insgesamt erhöhte psychiatrische Morbidität in den neuen Bundesländern. Depressive Symptome und der Gebrauch von illegalen Drogen und Medikamenten sind durchgängig in den alten Bundesländern häufíger nachzuweisen als in den neuen Bundesländern. Allenfalls ergaben sich für die Stichproben Ost für einzelne depressionstypische sowie einzelne psychovegetative Symptome und für Alkoholgebrauch statistisch signifikant erhöhte Werte. Da keine Diagnosekriterien erhoben wurden, muβ die Aussagekraft der Daten dahingehend eingeschränkt werden, daβ lediglich Indikatoren für psychische Auffälligkeiten erhoben wurden.