The associations between maternal smoking and nicotine dependence and patterns of smoking and nicotine dependence in offspring were examined in a large community-based sample of adolescents. Data were derived from baseline and 4-year follow-up assessments of 938 respondents aged 14–17 years at the outset of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study of adolescents and young adults and their parents respectively. Smoking and nicotine dependence in respondents were assessed using the Munich Composite International Diagnostic Interview (DSM-IV algorithms). Diagnostic information about smoking behavior in mothers was collected by independent direct diagnostic interviews with the mothers. In comparison to children of non- or occasionally smoking mothers, children of regularly smoking and nicotine-dependent mothers had higher probabilities of using tobacco as well as of developing nicotine dependence. For all ages under consideration, survival analyses revealed a higher cumulative lifetime risk of regular smoking and nicotine dependence among these children. Maternal smoking during pregnancy seems to represent an additional risk for these outcomes in children, specifically with regard to the risk of developing nicotine dependence. Associations were comparable for sons and daughters. Our findings show that maternal smoking predicts escalation of smoking, development of nicotine dependence, and stability of smoking behavior in children. Implications for specific intervention and prevention efforts are discussed.

Introduction: Faravelli et al. [1, 2] present findings on the lifetime, point and 1-year prevalence of mental disorders from their recent Sesto Fiorentino community survey in Italy. The publication of these study findings occurs at a time where some researchers and journal editors seem to have come to the conclusion that there is currently no further need for such cross-sectional studies on the prevalence of mental disorders. In fact, there have been pleas for a pause of such studies [3]. Highlighting several noteworthy features and findings from the survey of Faravelli et al. [1, 2], this editorial will challenge this attitude. The status, past and recent progress in the field of epidemiology of mental disorders will be critically discussed, in an attempt to underline the continued core role of descriptive epidemiological studies for our field and to identify future research needs.

Objective: We present the prevalence and incidence rates of alcohol, nicotine, and illicit substance use, abuse, and dependence in a sample of German adolescents and young adults. Patterns of onset, cohort trends, and use of various substance classes are also analyzed. Method: A prospective longitudinal epidemiological study with a representative sample of adolescents and young adults (n = 3,021; baseline age range = 14–24 years) was conducted in Munich, Germany. Participants were assessed between 1995 and 1999 with the Munich-Composite International Diagnostic Interview. Results: Cumulative lifetime incidence (up to age 28) of any substance abuse or dependence was 43.8%, and 12-month prevalence of any substance abuse or dependence was 24.4%. The lifetime incidence of nicotine dependence was most frequent (24.8%), followed by alcohol abuse (19.3%) and alcohol dependence (9.2%); 61.7% endorsed the regular use of a substance for at least one circumscribed period during their lifetime. Age-specific incidence rates and age at onset of substance use disorders differed by age cohorts. Furthermore, nicotine dependence was significantly associated with illicit substance use disorders (HR = 2.6, 95% CI 1.7–4.0). An interactive relationship between age, age at onset of nicotine dependence, and subsequent onset of illicit substance use disorders was found. Conclusions: Since the baseline investigation in 1995, high incidence rates of substance use disorders and substance use have been observed in this young German sample. Especially younger cohorts report significantly earlier ages at onset of abuse and dependence. There also seems to be a trend towards a secondary age at onset peak of nicotine dependence after the onset of illicit drug use disorders. Further investigations are needed to study these patterns in younger samples. However, results emphasize the need for a combined prevention of illicit drugs and nicotine dependence. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Hintergrund: Angststörungen gehören zu den häufigsten psychischen Störungen im Jugend- und Erwachsenenalter. Ein Großteil der Betroffenen bleibt meist unbehandelt. Informationen über die Behandlungswahrscheinlichkeit bei Jugendlichen und jungen Erwachsenen in Abhängigkeit von der Störungs- und Behandlungsart, Lebensalter, Geschlecht und Komorbidität liegen bisher nicht vor. Methode: In einer repräsentativen Stichprobe 14- bis 34-Jähriger aus dem Großraum München (Early Developmental Stages of Psychopathology Studie, N = 3021) werden die Prävalenz und Lebenszeitinzidenz von Angststörungen sowie ihre Behandlungsraten mittels M-CIDI erfasst und differenziert für Lebensalter, Komorbidität und Geschlecht präsentiert. Ergebnisse: 30% der Befragten berichteten mindestens eine Angststörung in ihrem Leben. Fast die Hälfte der Betroffenen (43%) suchte irgendeine Behandlung, ein Drittel (28%) suchte einen Psychotherapeuten auf. Für die meisten Angststörungen lagen hohe Quoten psychotherapeutischer Behandlungen vor (Range: 50–61%). Jugendliche berichteten seltener als Erwachsene irgendeine Behandlung, eine psychotherapeutische Behandlung, die Konsultation eines Psychiaters oder Hausarztes. Frauen nahmen häufiger eine Psychotherapie in Anspruch als Männer. Das Vorliegen einer komorbiden Angst- oder depressiven Störung erhöhte die Behandlungswahrscheinlichkeit. Diskussion: Verglichen mit europäischen Studien berichtete die Stichprobe relativ häufig eine Behandlung, auch eine psychotherapeutische. Dies kann eine Folge des großen Behandlungsangebotes in München sein. Dennoch bleibt der Großteil der jungen Betroffenen unbehandelt. Zur Prävention langfristiger Beeinträchtigungen sowie sekundärer psychischer Störungen sollte das Versorgungssystem verstärkt auf diese Bevölkerungsgruppe ausgerichtet werden. / Background: Anxiety disorders are among the most frequent mental disorders in adolescence and adulthood. Most of the affected individuals do not receive treatment. Information about treatment use among adolescents and young adults, differentiated for the kind of treatment and anxiety disorder, age, gender and co-morbidity, is still missing. Methods: In a representative sample of 14–34 year-old adolescents and young adults of the Munich area (Early Developmental Stages of Psychopathology study, N = 3,021) prevalence and lifetime incidence of anxiety disorders and treatment use are assessed using the M-CIDI and will be presented for age, co-morbidity and gender. Results: 30% of all participants reported at least one lifetime diagnosis of an anxiety disorder. Almost half of those affected (43%) received some kind of treatment; one third (28%) received psychotherapy. Psychotherapy use was frequent in most anxiety disorders (range: 50–61%). Older individuals more frequently reported any treatment, psychotherapy, consultations with psychiatrists or general practitioners. Women used psychotherapy more often than men. Co-morbid anxiety or depressive disorders increased the probability of treatment use. Discussion: As compared to European estimations, we found relatively high rates of treatment use. This may be due to the many treatment possibilities in the Munich area. Nevertheless, most young people affected do not receive treatment. Considering the long-term effects of anxiety disorders and in order to prevent secondary disorders, efforts should be increased to reach these young individuals.

Background: Findings are inconsistent regarding the degree to which depression may exert a negative impact on glycemic control in patients with type 2 diabetes. We therefore aimed to examine the longitudinal relationship between depression, behavioral factors, and glycemic control. Methods: In a prospective component of a nationally representative sample, 866 patients with type 2 diabetes aged ≧18 years completed a standardized assessment including a laboratory screening, questionnaires, and diagnostic measures. Subsequent to baseline (t0), patients were tracked over a period of 12 months (t1). Depression was assessed according to DSM-IV and ICD-10 criteria. Glycemic control was determined by levels of glycosylated hemoglobin (HbA1c); a level of ≧7% was judged as unsatisfactory. Regression analyses were performed to analyze the prospective relationship between depression, medication adherence, diabetes-related health behavior, and HbA1c. Results: Patients with depression at t0 revealed increased rates of medication nonadherence (adjusted OR: 2.67; CI: 1.38–5.15) at t1. Depression (adjusted regression coefficient: β = 0.96; p = 0.001) and subthreshold depression (β = 1.01; p < 0.001) at t0 also predicted increased problems with diabetes-related health behavior at t1. Adjusted ORs for poor glycemic control (HbA1c ≧7%) at t1 were also increased for patients with baseline depression (2.01; CI: 1.10–3.69). However, problems with medication adherence as well as problems with diabetes-related health behavior at t0 did not predict poor glycemic control at t1. Conclusions: In a prospective representative study of patients with type 2 diabetes, baseline depression predicted problems with medication adherence, problems with health-related behaviors, and unsatisfactory glycemic control at follow-up.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. Results: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. Conclusion: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.

Die vorliegende Arbeit beschreibt, wie depressive und somatoforme Beschwerden auf die global konzeptualisierte Lebenszufriedenheit wirken. Anhand einer bevölkerungsrepräsentativen Stichprobe (N=2510) wird diese Fragestellung analysiert. Ziel ist es zum einen zu klären, ob bereits subklinische Beschwerden zu deutlichen Einschränkungen der Lebenszufriedenheit führen und zum anderen, wie sich die beiden Beschwerdegruppen im Zusammenspiel auf die Lebenszufriedenheit auswirken. Somatische und depressive Symptome werden dimensional (subklinische Symptome eingeschlossen) untersucht und somatoforme und depressive Syndrome kategorial (auf ICD-10 Diagnose-Ebene) analysiert – quantifiziert jeweils mit dem Patient Health Questionnaire (PHQ). Lebenszufriedenheit wird mit den Fragen zur Lebenszufriedenheit (FLZ-M) gemessen. Univariate Kovarianzanalysen dienen zur statistischen Prüfung. Die Ergebnisse werden in einer Publikation dargestellt. Unter Berücksichtigung komorbider depressiver Symptome/Syndrome wirken sich somatische Symptome und somatoforme Syndrome nur auf einige Bereiche der Lebenszufriedenheit negativ aus. Eine dimensionale Auswertung ist sinnvoll, um den Einfluss subklinischer Symptome zu beschreiben.

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.

Cerebrovascular disease is a leading cause of disability and death worldwide, with about one third of stroke survivors initially suffering from communication disorders, including aphasia. Symptoms in aphasia vary from person to person, ranging from repeated failures in verbal expression to comprehension deficits that may occur in both the spoken and written modality. The current work synthesizes almost a decade of research on aphasia following left-hemispheric stroke in individuals with preserved right-hemispheric function: musical skills and formulaic expressions embedded in social interaction. Moving beyond the traditional scope of clinical linguistics, this work argues that preserved right-hemispheric function not only provides valuable resources in speech-language therapy, but also a possible foundation for psychotherapy in individuals with post-stroke aphasia and concomitant depression. An integrative summary introduces key developments in a line of research spanning from 2013 to 2021, to conclude with an outlook on forthcoming contributions and a commentary on the underlying conceptual framework. Each separate piece of research has been published previously in peer-reviewed journals. Here, the selected studies are assembled in an interdisciplinary context at the intersection of clinical neuroscience, speech-language pathology, and psychotherapy.

Background: Human African Trypanosomiasis (HAT) also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties. Results: The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM). The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions. Conclusion: Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross the bloodbrain- barrier, ethyl pyruvate could be considered as new candidate agent to treat the hemolymphatic as well as neurological stages of sleeping sickness.