Background: Psychological problems are common in cancer patients. For the purpose of planning psycho-oncological interventions and services tailored to the specific needs of different cancer patient populations, it is necessary to know to what extent psychological problems meet the criteria of mental disorders. The purpose of this study was to estimate the 12-month and lifetime prevalence rates of mental disorders in cancer patients. Methods: A representative sample of patients with different tumour entities and tumour stages (n = 2,141) in outpatient, inpatient and rehabilitation settings underwent the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients (CIDI-O). Results: The overall 12-month prevalence for any mental disorder was 39.4% (95% CI: 37.3–41.5), that for anxiety disorders was 15.8% (95% CI: 14.4–17.4), 12.5% (95% CI: 11.3–14.0) for mood disorders, 9.5% (95% CI: 8.3–10.9) for somatoform disorders, 7.3% (95% CI: 6.2–8.5) for nicotine dependence, 3.7% (95% CI: 3.0–4.6) for disorders due to general medical condition, and 1.1% (95% CI: 0.7–1.6) for alcohol abuse or dependence. Lifetime prevalence for any mental disorder was 56.3% (95% CI 54.1–58.6), that for anxiety disorders was 24.1% (95% CI: 22.3–25.9), 20.5% (95% CI: 18.9–22.3) for mood disorders, 19.9% (95% CI: 18.3–21.7) for somatoform disorders, 18.2% (95% CI: 16.6–20.0) for nicotine dependence, 6.4% (95% CI: 5.4–7.6) for alcohol abuse or dependence, 4.6% (95% CI: 3.8–5.6) for disorders due to general medical condition, and 0.2% (95% CI: 0.1–0.6) for eating disorders. Conclusions: Mental disorders are highly prevalent in cancer patients, indicating the need for provision of continuous psycho-oncological support from inpatient to outpatient care, leading to an appropriate allocation of direct personnel and other resources.

One of the main components underlying drug addiction is the emergence of tolerance. Although its development is a complex issue, and is believed to have both psychological and physiological connotations, it is clear that some physiological change must occur that would enable an organism to withstand drug concentrations lethal to a naïve system. The purpose of this thesis was to identify and study a physiological mechanism, whose characteristics were altered due to chronic exposure to ethanol. Vasopressin (AVP), whose primary function is to control water balance, release from the neurohypophysis is suppressed by an acute ethanol challenge. Therefore, I hypothesized; 1) that chronic ethanol exposure would reduce the normal suppression of AVP release during an acute ethanol challenge and 2) that the ion channels that are acutely sensitive to ethanol, involved in the control of AVP release, would exhibit a change in their ethanol sensitivity and characteristics. To study the hypothesis, I utilized the neurohypophysis from rats chronically exposed to ethanol and yoked controls to determine whether chronic exposure would modify the acute ethanol sensitivity of the neurohypophysial vasopressin release mechanism. I examined whether the long-term ethanol exposure affected the suppression of vasopressin release from either or both the intact neurohypophysis and the isolated neurohypophysial terminals. In addition, I investigated how chronic exposure affected two types of potassium channels, the ethanol sensitive large conductance Ca+2-activated (BK) channel and the fast inactivating (IA) channel known to be insensitive to physiologically relevant concentrations of ethanol. I was able to establish that chronic ethanol exposure reduced the suppression of vasopressin release by an acute ethanol challenge from both the intact neurohypophysis and the isolated neurohypophysial terminals. In addition, I discovered that oxytocin release was affected similarly. I concluded from this data that chronic exposure to ethanol affected a general mechanism, which controlled hormone release from the neurohypophysis, and that this mechanism could be isolated to the neurohypophysial terminals. I also used electrophysiological techniques to study ion channel characteristics of both the BK and IA potassium channels. I found that in naïve rats, BK channels were potentiated and IA channels insensitive to physiological relevant concentrations of ethanol. But in chronic ethanol-exposed rats the BK channels exhibited a reduced sensitivity to ethanol while IA channels were inhibited. In addition, the current density of the BK channel was significantly reduced. These results show that at least one characteristic of each potassium channel has been modified. This suggests that chronic exposure can not only modify the ethanol sensitivity of ion channels known to be ethanol-sensitive, but also those believed to be relatively insensitive. Therefore, since modifications in these channels have previously been shown to alter the duration and frequency of action potentials, I conclude that these ethanol-induced modifications play a role in the modified hormone release patterns observed in the chronically exposed rats.

Bakgrund: Den psykiatriska slutenvården ska hjälpa patienten att lindra lidande. Det är av betydelse hur personalen bemöter patienten samt hur patienten vill bli bemött för att de ska kunna bygga upp en relation till varandra. Mötet med patienten är en viktig del i vårdandet och hur vården upplevs. All psykiatriska slutenvård bör sträva efter att vara personcentrerad och individuellt anpassad. Syfte: Syftet var att undersöka patienters upplevelse av mötet med vårdpersonalen i den psykiatriska slutenvården. Metod: En systematisk litteraturöversikt med tolv kvalitativa artiklar. Resultat: Patienterna vill bli sedda, de vill att personalen ska vara tillgänglig och engagerad. Patienten önskar att personalen ska värna om patienternas integritet och autonomi. Patienterna vill att personalen tar kontakt med dem och försöker skapa en relation. Om patienterna har en god relation till personalen, har patienterna en större benägenhet att prata om deras psykiska hälsa. Patienterna kunde känna att personalen “gömde” sig när de hade andra arbetsuppgifter som inte var patientnära. Detta kunde leda till att vissa patienter blev agiterade och irriterade över att personalen var osynlig på avdelningen.  Det framkom att vissa patienter upplevde att personalen använde sig av maktmissbruk över dem, till exempel när någon undersökning skulle se eller bara ett samtal. Detta upplevde patienterna som att det hela tiden var vårdpersonalen som bestämde, vad som skulle hända och när. Slutsats: Vi som är ansvariga för omvårdnaden av patienterna som lider av psykisk ohälsa har ett stort ansvar, och det är att se till att alla patienter blir sedda, och får den uppmärksamhet var och en behöver. Vi måste prioritera våra patienter före exempelvis kontorsarbete eller att vara i köket. Vi måste bemöta patienterna med respekt och inte se dem som en sjukdom utom att de faktiskt är människor / Background: Psychiatric outpatient care should help the patient to relieve suffering. It is important how the staff responds to the patient and how the patient wants to be treated so that they can build up and relationship with each other. Meeting with the patient is an important part of caring and how they experience spring. All psychiatric inpatient care should strive to be person-centered and individually adapted. Purpose: The purpose was to explore the patients´ experience of the meeting with the healthcare staff in the psychiatric inpatient care. Method:A systematic literature review with twelve qualitative articles. Results: Patients want to be seen, they want staff to be available and engaged. The patient wants the staff to protect the patients' integrity and autonomy. Patients want the staff to contact them and assure to create a relationship. If patients have a god-relationship with staff, patients have a greater tendency to talk about their mental health. Patients could feel that the staff "hid" when they had other tasks that were not patient-friendly. This could cause some patients to become agitated and annoyed that staff were invisible in the ward. It turned out that some patients felt that the staff used abuse of power over them, for example when an investigation would see or just one call. The patients felt that it was always our staff who decided what would happen and when. Conclusion: We who are responsible for the care of patients suffering from mental illness have a great responsibility, and that is to make sure that all patients are looked after, and receive the attention everyone needs.We must prioritize our patients before, for example, office work or being in the kitchen. We have to treat patients with respect and not see them as a disease except that they are actually people.

Background: Although positive effects of physical activity on mental health indicators have been reported, the relationship between physical activity and the development of specific mental disorders is unclear. Method: A cross-sectional (12-month) and prospective-longitudinal epidemiological study over 4 years in a community cohort of 2548 individuals, aged 14–24 years at outset of the study. Physical activity and mental disorders were assessed by the DSM-IV Composite International Diagnostic Interview (CIDI) with an embedded physical activity module. Multiple logistic regression analyses controlling for age, gender and educational status were used to determine the cross-sectional and prospective associations of mental disorders and physical activity. Results: Cross-sectionally, regular physical activity was associated with a decreased prevalence of any and co-morbid mental disorder, due to lower rates of substance use disorders, anxiety disorders and dysthymia. Prospectively, subjects with regular physical activity had a substantially lower overall incidence of any and co-morbid mental disorder, and also a lower incidence of anxiety, somatoform and dysthymic disorder. By contrast, the incidence of bipolar disorder was increased among those with regular physical activity at baseline. In terms of the population attributable fraction (PAF), the potential for preventive effects of physical activity was considerably higher for men than for women. Conclusions: Regular physical activity is associated with a substantially reduced risk for some, but not all, mental disorders and also seems to reduce the degree of co-morbidity. Further examination of the evidently complex mechanisms and pathways underlying these associations might reveal promising new research targets and procedures for targeted prevention.

Aus der Einleitung: "The authors of the seven meta-structure papers in this issue have to be applauded for their inspiring attempt to suggest and elaborate a new meta-structure of mental disorders consisting of five ‘ clusters ’. At first sight this proposal seems to be considerably simpler than the current diagnostic classifications structure used by DSM-IV-TR (17 categories ; APA, 2000) and, in some parts, more convergent with the ICD-10 (10 categories ; WHO, 1993). Against the background of dissatisfaction expressed with the current diagnostic classification structure for mental disorders and its principles, the authors provide a selective critical review of relevant research. In particular, evidence is examined to address the question of whether current individual mental disorders differ sufficiently from each other and whether the current more fine-graded distinction of specific mental disorders and their grouping in 10 major classes according to ICD-10 and 17 in DSM-IV-TR is justified. To help answer this question, a prioricriteria were chosen in the form of a wide range of ‘validators ’ grouped into so-called ‘causal’ risk factors (i.e. shared genetic risk factors, familiality, shared environmental risks, shared neural substrates, shared biomarkers, shared temperamental antecedents) and factors thought to be more likely to reflect the clinical picture itself (shared abnormalities of cognitive and emotional processing, symptom similarity, rates of co-morbidity, course, treatment response). The results of this impressive exploration are interpreted to suggest a substantial reduction of the current major classes to five clusters and a fairly large residual category of disorders not yet assigned. Particularly noteworthy examples for classificatory changes associated with the proposed meta-structure involve: the suggestion to group anxiety, somatoform and depressive disorders together under the term ‘emotional disorders ’ ; the allocation of bipolar disorders to the ‘psychotic cluster ’ ; and the formation of a broad externalizing cluster that comprises substance use disorders, some of the personality disorders and impulse control disorders. [...]"

The role of comorbidity as a risk for suicide attempts is investigated in a random sample of 3021 young adults aged 14–24 years. The M-CIDI, a fully standardized and modified version of the Composite International Diagnostic Interview, was used for the assessment of various DSM-IV lifetime and 12-month diagnoses as well as suicidal ideation and suicide attempts. Of all suicide attempters, 91% had at least one mental disorder, 79% were comorbid or multimorbid respectively and 45% had four or more diagnoses (only 5% in the total sample reached such high levels of comorbidity). Suicide attempters with more than three diagnoses were 18 times more likely (OR = 18.4) to attempt suicide than subjects with no diagnosis. Regarding specific diagnoses, multivariate comorbidity analyses indicated the highest risk for suicide attempt in those suffering from anxiety disorder (OR = 4.3), particularly posttraumatic stress disorder followed by substance disorder (OR = 2.2) and depressive disorder (OR = 2.1). Comorbidity, especially when anxiety disorders are involved, increases the risk for suicide attempts considerably more than any other individual DSM-IV diagnoses.

This special issue was prepared within the framework of the European College of Neuropsychopharmacology (ECNP) Task Force on “Size and Burden of Mental Disorders in Europe”. The core aim of the Task Force was to describe the prevalence and the burden of treated and untreated mental disorders in all European member states and to highlight needs for further research. Ten state-of-theart epidemiological papers summarize the outcome of this project, making an attempt to provide for the first time ever prevalence estimates for a wide range of mental disorders, as well as for dementia and Parkinson’s disease in 28 European countries. These data also provide input for the European Brain Council (EBC, http://www.ebc-eurobrain. net) Initiative “Cost of Disorders of the Brain in Europe” aiming at estimating the cost of major classes of mental, neurological and neurosurgical disorders and conditions in Europe.

Background: Perinatal depression affects 1 in 7 childbearing individuals and remains underdiagnosed and undertreated. Individuals with a psychiatric history are at increased risk of perinatal depression, and little is known about how experiences with the mental health care pathway may differ between these individuals and those without a psychiatric history. Methods: This was a secondary analysis of data from the PRISM (PRogram in Support of Moms) study, a cluster randomized controlled trial of two interventions for perinatal depression. Care access and barriers to care were evaluated in perinatal individuals who screened positive for depression using the EPDS (N=280). Results: Individuals with no psychiatric history prior to pregnancy (N=113), compared to those with such history (N=267), were less likely to be screened for perinatal depression, and less likely to be offered a therapy referral, though equally likely to attend when referred. In adjusted models, those without a psychiatric history had 0.59 times the odds of attending therapy (95% CI 0.28-1.25), 0.23 times the odds of utilizing medication (95% CI 0.11-0.47), and overall, 0.22 times the odds of receiving any depression care (95% CI 0.11-0.43). Participants reported on average 3 barriers as preventing them from receiving care “a lot” or “quite a lot”. The proportion of individuals endorsing each barrier was similar between groups, excepting “concerns about treatments available” and “thinking the problem would get better by itself”, which were more prevalent in those without a prior psychiatric history. Conclusions: There exist meaningful differences in the way perinatal individuals access care for depression based on psychiatric history. An understanding of these differences is crucial in addressing gaps between mental health care need and care receipt.

Background: Per definition, traumatic events include exposures to death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence. Exposure to traumatic events is associated with persistent alterations in biological and psychological processes that are involved in the etiology of mental disorders. In fact, traumatic events are associated with a higher risk for various mental disorders such as posttraumatic stress disorder (PTSD) and substance use disorders, but also with treatment resistance. Thus, it is crucial to develop early interventions to prevent these adverse trauma-related outcomes. However, existing pharmacological and psychological early intervenions only have a limited efficacy so far. A major reason is that only a minority of trauma-exposed individuals actually develops adverse consequences making universally applied interventions ineffective. Thus, it is crucial to identify moderators of adverse responses to trauma exposure. Aims: This thesis aimed at (1) providing estimates on the prevelance of traumatic event exposure and trauma-related mental disorders for the general population and high-risk populations and (2) investigating moderators of adverse mental health consequences following traumatic event exposure. The following potential moderators were investigated: (i) the susceptibility to others‘ emotions, (ii) childhood traumas, (iii) biological stress markers and (iv) a specific genetic polymorphism involved in the degradation of monoamines (i.e. MAOA gene). These investigations were conducted with respect to differenct outcomes relevant in the processing of traumatic events including the initial affective and biological reaction, mental disorder symptoms (focusing on PTSD and alcohol use symptoms) and treatment response. Methods: To answer the research questions, different methods and designs were applied. First, epidemiological data from a national study program in German soldiers deployed to Afghanistan were used. These data included diagnostic interview data as well as biological markers. Second, an experimental study with a randomized trauma analogue design was used to investigate moderators of acute trauma responses. Third, a genetic moderator of trauma effects on treatment response was investigated using data from a multi-center trial of exposure-based cognitive behavioral therapy of panic and agoraphobia patients. Main results: Only a small minority of trauma-exposed individuals develops mental disorders. This also applies to populations with a high risk for multiple and/or severe trauma exposure. The investigations of potential moderators suggeted that individuals with a higher susceptibility to negative emotions of others show a higher stress reactivity after trauma exposure. Males with childhood traumas show a higher increase in alcohol craving after trauma exposure. Moreover, individuals with lower basal cortisol levels have a higher risk of increased PTSD symptoms and alcohol use following trauma exposure. Finally, a subgroup of traumatized female panic disorder patients with the low-active variant of the MAOA gene benefits less from exposure-based psychotherapy. Conclusions: These findings suggest novel targets for moderating factors and show the relevance of previously discovered moderators in novel contexts. Some of the identified moderators represent promising targets for risk markers before or in the direct aftermath of traumatic event exposure. Further research is needed to comfirm the suggested moderators and to investigate the exact mechanisms involved. Moreover, future studies should aim at integrating findings on different moderators and translate them into effective risk assessments and targeted early interventions. / Hintergrund: Traumatische Ereignisse sind definiert als Konfrontation mit tatsächlichem oder droghenden Tod, ernsthafter Verletzung oder sexueller Gewalt. Das Erleben traumatischer Ereignisse ist mit andauernder Veränderungen in biologischen und psychischen Prozesssen assoziiert, welche eine bedeutende Rolle in der Ätiologie psychischer Störungen spielen. Tatsächlich sind traumatische Ereignisse mit einem höheren Risiko für zahlreiche psychische Störungen assoziiert, darunter vor allem die Posttraumatische Belastungsstörung (PTBS) und Substanzstörungen. Zudem zeigen Personen mit traumatischen Erfahrungen häufiger ein schlechteres Ansprechen auf Behandlungen. Die Entwicklung möglichst früher Inteventionen zur Vermeidung dieser Traumafolgen ist somit von großer Bedeutung. Allerdings sind bestehende frühe Interventionen nach traumatischen Eriegnissen bislang nur sehr begrenzt effektiv. Ein wesentlicher Grund hierfür besteht darin, dass überhaupt nur ein kleiner Anteil von traumatisierten Personen negative Folgen entwickelt. Es ist demnach entscheidend, solche Faktoren zu identifizieren, die das Risiko negativer Folgen nach traumatischen Ereignissen moderieren. Ziele: (1) Darstellung der Prävalenz von traumatischen Ereignissen und trauma-bezogenen psychischen Störungen für die Allgemeinbevölkerung und für spezifische Risikopopulationen, sowie (2) die Untersuchung von Moderatoren negativer Traumafolgen, wobei folgende potenzielle Moderatoren untersucht wurden: (i) die Ansteckbarkeit für die Emotionen anderer, (ii) Kindheitstraumata, (iii) biologische Stressmarker und (iv) ein genetischer Polymorphismus, der beim Abbau von Monoaminen involviert ist (MAOA Gen). Diese Moderatoren wurden in Bezug auf unterschiedliche Outcomes untersucht, welche Aspekte der Verarbeitung traumatischer Ereignisse darstellen: die unmittelbare emotionale und biologische Reaktion, Symptome psychischer Störungen (mit Fokus auf PTBS und Alkoholkonsum) sowie das Ansprechen auf Behandlung. Methoden: Zur Beantwortung der Fragestellungen wurden verschiedene Methoden und Studiendesigns genutzt. Diese beinhalteten zum einen epidemiologische Daten eines bundesweiten Studienprogramms bei deutschen Soldaten mit Militäreinsatz in Afghanistan. Diese Daten umfassten diagnostische Interviews sowie biologische Stressmarker. Weiterhin wurde eine experimentelle randomisierte Analogstudie durchgeführt, um Moderatoren von initialen Traumareaktionen zu identifizieren. Schließlich wurden Daten einer Multi-Center Therapiestudie bei Patienten mit Paniskstörung und Agoraphobie verwendet, um die Moderation des Effekts vorangegangener Traumatisierung auf den Therapieerfolg durch einen genetischen Faktor (MAOA Gen) zu untersuchen. Hauptergebnisse: Nur ein geringer Anteil von Betroffenen entwickelt nach der Konfrontation mit einem trauamtischen Ereignis psychische Störungen. Dies gilt auch in Populationen mit einem erhöhten Risiko für multiple und schwere Traumata. Die durchgeführten Studien zur Identifikation von Moderatoren weisen darauf hin, dass Personen mit einer erhöhten Ansteckbarkeit für negative Emotionen anderer eine stärkere initiale Stressreaktion bei Traumaexposition aufweisen. Darüber hinaus zeigen Männer mit Traumatisierung in der Kindheit einen stärkeren Anstieg von Alkoholcraving nach der Konfrontation mit einem akuten Trauma. Weiterhin sind niedrige basale Cortisol Level mit einem höheren Risiko für einen Anstieg der PTBS Symptomatik sowie im Alkoholkonsum nach traumatischen Ereignissen assoziiert. Schließlich gibt es Hinweise auf geringere Therapieeffekte bei vorangegangener Traumatisierung bei einer Subgruppe von weiblichen Patientinnen mit Panikstörung mit der niedrig aktiven Variante des MAOA Gens. Schlussfolgerungen: Es konnten neue Kandidaten für mögliche Moderatoren identifiziert sowie die Relevanz bekannter Moderatoren in neuen Kontexten gezeigt werden. Einige dieser Moderatorvariablen stellen vielversprechende Ziele für Risikomarker vor und unmittelbar nach der Konfrontation mir traumatischen Ereignissen dar. Weitere Forschung ist nötig, um die hier identifizierten Moderatoren zu bestätigen und die zugrundeliegenden Mechanismen aufzudecken. Zudem sollte künftige Forschung die Befunde zu verschiedenen Moderatoren integrieren um daraus effektive Risikobewertungen und gezielte Frühinterventionen ableiten zu können.

While it is clear that most drugs of abuse act to increase extracellular dopamine levels in the nucleus accumbens (NAc), the molecular mechanisms mediating this process vary depending on the molecular target each drug acts on. The rewarding properties of most drugs of abuse including cocaine, amphetamine, and heroin have been well established for some time; however, the molecular mechanisms by which ethanol acts to mediate reward have not been fully elucidated. In this thesis, I have examined the role of nicotinic acetylcholine receptors (nAChRs), known molecular targets for nicotine addiction, in mediating the initial rewarding properties of alcohol. Using a mouse model of voluntary ethanol consumption called Drinking in the Dark (DID), in combination with nAChR pharmacology and mouse genetics, we have provided further evidence for the role of nAChRs in mediating the initial rewardingproperties of ethanol. Because of the vast number of possible functional nAChR subtypes present in the brain, I sought to investigate which subtype of nAChR may be responsible for ethanol reinforcement. To accomplish this, I used twocomplementary nAChR mouse models. The first is a knock-out line that does not express the α4 subunit (α4 KO) and the second is a knock-in line that expresses α4* nAChRs that are hypersensitive to agonist (Leu9′Ala). We have also shown, for the first time, that a specific nAChR subtype, those that contain the α4 subunit (α4*), mediate voluntary ethanol consumption and reward. Next, I examined the role of α4* nAChRs in modulating voluntary ethanol consumption after systemic administration of the FDA approved smoking cessation drug varenicline, a partial agonist of α4* nAChRs. We showed that varenicline and nicotine both reduced acute ethanol consumption in an α4* nAChR dependent mechanism. Taken together, our data indicate that activation of α4* nAChRs is necessary and sufficient for reduction of ethanol consumption and further supports the hypothesis that α4* nAChRs are molecular targets for alcohol cessation therapies.