Open Access

Fear is an emotional state, characterized by the activation of a defense system that is designed to ensure the organism’s survival. This system enables a rapid recognition of threats and organizes defensive response patterns in order to adaptively cope with the threatening environment. Yet, to ensure its flexibility under changing environmental conditions, inhibitory pathways exist that modulate the activation of this defense system, if a previously threatening cue no longer predicts any harm – a memory-formatting process referred to as fear extinction, leading to a reduction of defensive responding. Fear extinction is presumed to at least partially underlie exposure treatment of anxiety disorders, which is why the facilitation of this learning process may promote such treatment’s efficacy. Animal models suggested, that the stimulation of the vagus nerve or the superior colliculus (SC) – a midbrain structure mediating visual attentional processing – target these inhibitory extinction pathways and, thus, facilitate fear extinction. However, as it is unclear whether similar mechanisms exist in humans, this thesis manuscript examined how non-invasive stimulation of these inhibitory pathways by transcutaneous vagus nerve stimulation (tVNS) or SC-recruiting visual attentional manipulation impact on human fear extinction. To this end, we conducted three studies using multiple-day single-cue fear conditioning and extinction paradigms. First, we elaborated on fear that is established in these paradigms by examining defensive responding that is elicited by an innocuous conditioned stimulus, which has either been paired (fear learning group) with an aversive unconditioned stimulus (US; an electric shock) or was unpaired (control group; study 1). During the following extinction training, either tVNS vs. sham stimulation was applied (study 1, study 2) or participants were instructed, to either generate saccadic eye movements (strong SC activation) vs. smooth eye pursuits (low SC activation; study 3). During subsequent sessions, extinction consolidation as well as the short- and long-term extinction recall was tested (study 2, study 3). Conditioned fear in the fear learning group was characterized by elevated cognitive risk assessments (US-expectancy ratings), as well as increased cardiac deceleration and startle reflex potentiation compared to controls. Cardiac deceleration was positively correlated to startle potentiation, but was decoupled from cognitive risk assessments (study 1). Initial, short- and long-term extinction of these defensive responses was facilitated by tVNS on all three response levels (cognitive, physiological, behavioral; study 1, study 2). In contrast, saccades facilitated initial extinction only for physiological and behavioral elements of the defensive response pattern, while extinction consolidation and recall was impaired by any eye movement manipulation (study 3) for physiological and behavioral indicators of defensive responding. Taken together, the data of the experimental series suggest, that on a behavioral level, conditioned fear may best be conceived as attentive immobility – a defense strategy elicited by inevitable distal threats, that is uniformly expressed across species and is accompanied by cardiac deceleration and startle reflex potentiation. In addition, it was shown that such rather automatic defensive adaptations are independent from verbally expressed threat expectancies. As expected, tVNS impacted on fear extinction on both levels, strongly in line with the suggestion, that vagal stimulation activates cortical and subcortical neural pathways involved in extinction learning, consolidation and recall. TVNS may, thus, be a promising adjuvant for exposure treatment of mental disorders. In contrast, SC-recruiting visual attentional manipulation only affected subcortically mediated defensive responding, in line with rodent findings, indicating that the SC specifically inhibits subcortical parts of the neural defense system. However, as extinction recall was impaired by any type of visual attentional manipulation, this appeared to have functioned as a form of avoidance, initially attenuating fear but preventing extinction consolidation and, thus, impairing sustained fear reduction. Both non-invasive stimulation techniques may therefore increase initial defensive flexibility in the face of no-longer threat-signaling stimuli, but only tVNS may achieve long-term effects on multiple response levels.

Ungeachtet der Alltagsrelevanz ist die empirische Evidenz zur Regulation selbstbewer-tender Emotionen im Forschungsfeld unterrepräsentiert. In Dual-Process-Ansätzen wurden Zusammenhänge zwischen Emotionen, kognitiver Emotionsregulation und Entscheidungs-verhalten in moralischen Konflikten modelliert. Jüngere Befunde legen nahe, dass habituelles und experimentell induziertes Reappraisal – mediiert über die emotionale Erregung – positiv mit konsequentialistischen Urteilen und Entscheidungen assoziiert sind. Ziel der Arbeit ist es, den Einfluss kognitiver Emotionsregulation auf das Entscheidungs-verhalten in moralischen Alltagsdilemmata zu untersuchen. Welche kognitiven Strategien kommen bei der Schuld- und Schamregulation zum Einsatz? Welche Wirkung entfalten sie auf verschiedene Outcomes (emotionales Erleben, Entscheidungsverhalten)? Inwiefern unterscheiden sich Formen und Taktiken des Reappraisal in ihrer Wirkung? In einem ersten Schritt wurden schuld- und schamauslösende Dilemmata entwickelt und anhand definierter Kriterien selektiert. Eine Studienreihe betrachtete den Einfluss habitueller, kognitiver Emotionsregulation und experimentell manipuliertem Reappraisal auf das Entscheidungsverhalten in diesen Dilemmata. Tendenziell begünstigten funktionale Strategien aus der Reappraisal-Familie konsequentialistische Entscheidungen. Der Media-tionseffekt über die emotionale Erregung konnte nicht repliziert werden. Eine zweite Studien-reihe mit explorativer Methodik beabsichtigte, die Phänomenologie von Reappraisal-Taktiken bei einem moralischen Entscheidungskonflikt abzubilden. Mittels eines Kategoriensystems konnten problemorientierte und externalisierende Reappraisal-Taktiken identifiziert werden. Limitationen der Untersuchungen und Anknüpfungspunkte für zukünftige Forschung werden ebenso diskutiert wie Implikationen der Ergebnisse für die klinische und forensische Praxis.

Background: To reduce the burden of disease attributable to alcohol, screening for at-risk alcohol use in the general population is recommended. Screening is usually carried out at only one point in time although individual alcohol use may change over time and self-reported consumption may be biased by underreporting. However, there are gaps in research on temporal variability of alcohol use. Therefore, this cumulative dissertation investigated (1) changes in drinking patterns within 4 weeks; (2) changes in screening results within 12 months and factors predicting a transition from low-risk to at-risk alcohol use; (3) whether underreporting can be reduced by prompting respondents to recall their alcohol use in the past week prior to screening. Methods: Participants were adults from the general population recruited in a municipal registry office. For the first paper, 288 alcohol users were assessed four times using Timeline Follow-Back, each one week apart. Changes in drinking patterns were analyzed using latent transition modeling. For the second paper, 831 control group participants of a randomized controlled trial were screened for at-risk alcohol use at baseline, 3, 6, and 12 months later using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C). The transition from low-risk to at-risk alcohol use was predicted using logistic regression. For the third paper, 2,379 alcohol users were screened for at-risk alcohol use using the AUDIT-C, either before or after receiving the prompt to recall their past week alcohol use. Data were analyzed using logistic regression. Results: Within 4 weeks, 35 percent of alcohol users changed their drinking pattern. Changes were more likely for individuals with moderate or heavy compared to light drinking. Within 12 months, 30 percent of alcohol users changed their screening result. Changes were more likely for at-risk compared to low-risk alcohol users. Transitioning from low-risk to at-risk alcohol use was more likely for women (vs. men; Odds Ratio, OR = 1.66), 18- to 29-year-old adults (vs. 30- to 45-year-old adults; OR = 2.30), and individuals reporting two or more drinking days in the past week (vs. less than two; OR = 3.11). When respondents were prompted to recall their alcohol use in the past week prior to screening, they were less likely to report at-risk alcohol use compared to when the screening was conducted without prior prompt (OR = 0.83). Conclusions: One in three alcohol users changed their consumption, some of them even within a period as short as 4 weeks. These changes might compromise the validity of screening that is commonly based on a single assessment of typical alcohol use. Furthermore, underreporting cannot be reduced by prompting individuals to recall their alcohol use in the past week prior to the screening for at-risk alcohol use. Rather, consecutive questionnaires addressing different aspects of alcohol use within a single survey might be a potential source of bias.

Background: Depressive disorders are highly prevalent and disabling diseases. Epidemiological studies have shown that they often co-occur with addictive behaviors, which in part might be explained by common risk factors. Rumination might be such a risk factor. Comorbidity can have substantial adverse effects for those affected. Thus, combined treatment approaches are needed. These should not be restricted to individuals with clinical disorders. In light of an apparent treatment gap, new treatment approaches that provide widespread access to evidence-based treatments need to be explored. In recent years, e-health interventions received a lot of attention. With their potential to be widely disseminated, they might be suitable to provide population-based intervention approaches. Developing population-based interventions might present special challenges to intervention developers, for example, in terms of intervention design or the selection of samples to preliminary test interventions. This thesis explored the application of e-health interventions in the treatment and prevention of depressive symptoms and addictive behaviors. Its first aim was to provide an overview on publicly accessible evidence-based e-health interventions for the treatment and prevention of depressive symptoms (study 1). The second aim was to test the feasibility, acceptability and potential effectiveness of a newly developed computer-based expert system intervention simultaneously targeting hazardous alcohol consumption and depressive symptoms and to investigate the importance of the sample selection when preliminary testing interventions (study 2). The third aim was to further investigate rumination with its subfactors brooding and reflection as a common cause of depression and addictive behaviors and thus as a potential target for combined interventions by analyzing its associations with symptoms of pathological gambling (SPGs; study 3). Methods: This thesis provides a summary of different working steps in the process of developing and testing a computer-based intervention for health care patients (HCPs) with comorbid hazardous alcohol consumption patterns and depressive symptoms. In study 1, a systematic literature search was conducted to identify evidence-based e-health interventions for depressive symptoms. Interventions were considered for further inspection if studies provided evidence for at least small intervention effects and if the interventions were accessible to at least selected groups of individuals. For study 2, 2773 consecutive HCPs were screened for hazardous drinking and depressive symptoms. Of the 41 HCPs who were offered to participate in the study, 27 (65.9%) consented. To investigate the importance of the sample selection when preliminary testing interventions, HCPs were compared to media recruited volunteers (MVs). Over a period of 6 months, study participants received 6 individualized counselling letters and weekly short messages. Pre-post data were analyzed for 30 participants (15 HCPs, 15 MVs). Intervention acceptability was assessed in post-intervention interviews conducted with 32 study participants. In study 3, cross-sectional data of 506 (80.4% male) individuals aged 14 to 64 years with a history of gambling problems were analyzed. Associations between the rumination subfactors and SPGs across different levels of problem gambling severity were investigated by means of sequential quantile regression. Results: In study 1, 37 publicly accessible evidence-based e-health interventions for depressive symptoms were identified. Most interventions (81.1%) were available in English. For the German language area, only 3 interventions were identified. In study 2, HCPs and MVs reduced regular binge drinking (HCPs: p = 0.016; MVs: p = 0.031) and depressiveness (HCPs: p = 0.020; MVs: p < 0.001). MVs further reduced average daily consumption (p = 0.034). Both subsamples rated the intervention positive. Compared to HCPs, MVs rated the alcohol module more favorably (p = 0.012). Intervention usage was higher in MVs than in HCPs (p = 0.013). Study 3 showed that at the median, ruminative brooding was positively associated with the severity of problem gambling after controlling for covariates (p = 0.005). Along the distribution of problem gambling severity, findings did hold for all but the lowest severity level. Ruminative reflection was not associated with problem gambling severity at the median (p = 0.347). Conclusions: E-health interventions show great potential in the treatment and prevention of depressive symptoms and addictive behaviors. However, more research is needed to clarify how to make the most of this potential. Important questions that remain to be answered include, for example, how to best provide e-health interventions to those in need or how to design interventions in order to maximize their reach and thus their public health impact. This thesis showed that 1) publicly accessible evidence-based e-health interventions for depressive symptoms were available. However, the supply in the German language area was low. 2) The computer-based expert system intervention targeting hazardous alcohol consumption and depressive symptoms was technically and logistically feasible, acceptable, and may have the potential to reduce hazardous drinking and depressive symptoms in different populations, including populations unselected in terms of their motivation to change. To avoid biased conclusions about the potential of interventions, intervention developers should preliminary test interventions on intended target populations. 3) Rumination might be important in the development and maintenance of addictive behaviors. With its relations to depression and addictive behaviors, it should be considered as a target for future combined interventions.

Transition wird bezeichnet als zielgerichteter, geplanter Wechsel der Kinder und Jugendlichen mit chronischen Erkrankungen von dem kindzentrierten zum erwachsenenzentrierten Gesundheitssystem (Blum et al., 1993). Transition soll ein strukturierter, gut implementierter, geplanter und absichtsvoller Prozess sein, welcher die Jugendlichen mit chronischen Erkrankungen, ihre Eltern und die involvierten Gesundheitsexpert*innen befähigt, den Wechsel von der Pädiatrie zur Erwach¬senen¬medizin erfolgreich abzuschließen (Blum et al., 1993; Huang et al., 2014; Kennedy et al., 2007). Es ist notwendig den Prozess der Transition an die individuellen Bedürfnisse der Jugendlichen anzupassen und somit deren Unterstützung flexibler zu gestalten zu können, um dies zu erreichen, werden entsprechende Instrumente zur Erfassung von Konstrukten in der Transition benötigt. Von besonderem Interesse ist die Transitionsbereitschaft von Jugendlichen mit chronischen Erkrankungen. Um die individuelle Bereitschaft zur Transition eines Jugendlichen mit chronischer Erkrankung feststellen zu können, fehlen zudem änderungssensitive Instrumente, die zugleich auch allgemein anwendbar sind, sodass eine Vergleichbarkeit zwischen verschiedenen Erkrankungen bzw. Versorgungsbereichen ermöglicht wird. Von diesem methodischen Defizit der Transitionsforschung ausgehend werden in der vorliegenden Arbeit folgende Konstrukte sowie deren Operationalisierung und Erfassung im Kontext der Transition psychometrisch genauer analysiert: gesundheitsbezogene und krankheitsspezifische Lebensqualität, Versorgungszufriedenheit, Transitionskompetenz, Patientenaktivierung und Patienten-empowerment. Zusammenfassend zeigt sich, dass die Konstrukte krankheitsspezifische Lebens-qualität, Versorgungszufriedenheit, Transitionskompetenz, Patientenaktivierung und Patienten¬empowerment zur Erfassung von transitionsbezogenen Veränderungen bei Jugendlichen mit chronischen Erkrankungen geeignet sind. Lediglich die Erfassung die gesundheitsbezogene Lebensqualität sollte für zukünftige Studien geprüft werden.