167 research outputs found
Psychosocial stress experience and DNA methylation in humans - implications for stress-adaptation and -resilience
No full textAbstract: Background: Psychosocial stress, especially early in life, is a risk factor for mental disorders. Recent evidence suggests that stress-related changes in epigenetic patterns, including DNA methylation, could mediate this association.
Aim: to examine a potential association between psychosocial stress exposure and DNA methylation of two stress-related genes: the oxytocin receptor (OXTR) and the brain-derived neurotrophic factor (BDNF).
Methods: We investigated DNA methylation in three target sequences: OXTR1, OXTR2 and BDNF. The psychosocial stressors included: (1) maternal stress during pregnancy (prenatal stress, N=39); (2) low versus high maternal care during childhood (maternal care, N=85) and (3) acute psychosocial stress (N=83). In the prenatal stress study, DNA methylation of OXTR1 was quantified in cord-blood cells. In the maternal care and acute psychosocial stress study, DNA methylation of OXTR1, OXTR2 and BDNF was quantified in peripheral blood cells of adults.
Results: (1) Several indicators of increased prenatal stress predicted higher DNA methylation of OXTR1. (2) Adults reporting low maternal care showed increased OXTR2 DNA methylation compared to those reporting high maternal care. (3) Exposure to acute psychosocial stress was associated with dynamic changes in DNA methylation of OXTR – DNA methylation increased from pre- to post-stress in OXTR1 and decreased from post-stress to follow up in OXTR1 and OXTR2. Some of these changes might have been due to variations in blood cell count.
Discussion: Exposure to psychosocial stress was associated with target sequence-specific changes in OXTR DNA methylation. These results could contribute to our understanding of epigenetic processes involved in stress-adaptation. ---------- Zusammenfassung:
Hintergrund: Psychosozialer Stress, insbesondere während der frühen Entwicklung, ist ein
Risikofaktor für psychische Erkrankungen. Dieser Zusammenhang könnte durch stress- assoziierte epigenetische Veränderungen, z.B. in der DNA Methylierung, mediiert werden.
Ziel: ein potentieller Zusammenhang zwischen verschiedenen psychosozialen Stressoren und der DNA Methylierung zweier stress-assoziierter Gene zu untersuchen: dem Oxytozin Rezeptor (OXTR) und dem Brain-Derived Neurotrophic Factor (BDNF).
Methode: DNA Methylierung wurde in drei DNA Zielsequenzen gemessen: OXTR1, OXTR2 und BDNF. Die untersuchten psychosozialen Stressoren waren: (1) mütterlicher Stress während der Schwangerschaft (pränataler Stress, N=39); (2) mütterliche Zuwendung in der Kindheit (N=85) und (3) akuter psychosozialer Stress im Erwachsenenalter (N=83). In der Studie zu pränatalem Stress wurde DNA Methylierung von OXTR1 im Nabelschnurblut gemessen; in den Studien zu mütterlicher Zuwendung und akutem psychosoziale Stress wurde DNA Methylierung von OXTR1, OXTR2 und BDNF in peripherem Blut gemessen.
Resultate: (1) Mehrere Indikatoren von pränatalem Stress sagten eine stärkere OXTR1 DNA Methylierung vorher. (2) Erwachsene, welche von wenig mütterlicher Zuwendung berichteten, hatten eine stärkere Methylierung in OXTR2 im Vergleich zu denjenigen mit mehr Zuwendung. (3) Akuter psychosozialer Stress war mit dynamischen Veränderungen in OXTR DNA Methylierung assoziiert: eine Erhöhung von Prä-Stress zu Post-Stress in OXTR1 und eine Erniedrigung von Post-Stress zu Follow-Up in OXTR1 und OXTR2, wobei einige dieser Veränderungen allenfalls durch Variationen in der Blutzell-Verteilung zustande kamen.
Diskussion: Psychosozialer Stress war assoziiert mit Veränderungen in der DNA Methylierung des OXTR. Die Resultate könnten zu einem besseren Verständnis von epigenetischen Stress-Adaptionsmechanismen beitragen
Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study
No full textBackground: Identifying risk factors for adverse health outcomes in children is important. The intrauterine environment plays a pivotal role for health and disease across life. Objectives: To conduct a comprehensive study to determine whether common psychosocial stress during pregnancy is a risk factor of a wide spectrum of pediatric diseases in the offspring. Methods: The study was conducted in a population-based sample of mothers with live singleton births (N=66203, 71.4% of those eligible) from the Danish National Birth Cohort, using prospective data. We estimated the association between maternal stress during pregnancy (classified based on two a priori defined indicators of common stress forms, life stress and emotional stress) and offspring diseases during childhood (grouped into 16 categories of ICD-10 diagnoses based on data from national registries), controlling for maternal stress after pregnancy. Results: Median age at end of follow-up was 6.2 (3.6-8.9) years. Life stress (highest compared to lowest quartile) was associated with an increased risk of conditions originating in the perinatal period [odds ratio (OR)=1.13; 95% confidence interval (CI)=1.06-1.21] and congenital malformations (OR=1.17; CI=1.06-1.28), and of the first diagnosis of infection [hazard ratio (HR)=1.28; CI=1.17-1.39], mental disorders (age 0-2.5 years: HR=2.03; CI=1.32-3.14), eye (age 0-4.5 years: HR=1.27; CI=1.06-1.53), ear (HR=1.36; CI=1.23-1.51), respiratory (HR=1.27; CI=1.19-1.35), digestive (HR=1.23; CI=1.11-1.37), skin (HR=1.24; CI=1.09-1.43), musculoskeletal (HR=1.15; CI=1.01-1.30), and genitourinary diseases (HR=1.25; CI=1.08-1.45). Emotional stress was associated with an increased risk for the first diagnosis of infection (HR=1.09; CI=1.01-1.18) and a decreased risk for the first diagnosis of endocrine (HR=0.81; CI=0.67-0.99), eye (HR=0.84; CI=0.71-0.99), and circulatory diseases (age 0-3 years: HR=0.63; CI=0.42-0.95). Conclusions: Maternal life stress during pregnancy be a common risk factor for impaired child health. The results suggest new approaches to reduce childhood diseases
The comorbidity of anxiety disorders and physical diseases : an epidemiological approach
No full textAbstract
Background: Anxiety disorders are highly comorbid with other mental disorders. This has important implications for individuals’ burden, etiology of the comorbid diseases and treatment. Knowledge about the comorbidity with physical diseases in the community, however, is limited, especially for specific anxiety disorders. This dissertation evaluates the comorbidity of specific anxiety disorders and noncommunicable and communicable physical diseases in the general population. Further, it investigates the association of comorbidity with measures of burden, namely, quality of life and disability.
Method: Data of the German Health Interview and Examination Survey (GHS), a representative general population survey from Germany with 4,181 subjects aged 18-65 years, were used. Anxiety disorders were diagnosed using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI), noncommunicable physical diseases were assessed through a self-report questionnaire and a standardized medical interview, and communicable physical diseases through a self-report questionnaire.
Results: Both obsessive-compulsive disorder (OCD) and specific phobia were associated with migraine and respiratory diseases. Additionally, subthreshold forms of OCD were associated with specific noncommunicable physical diseases. Agoraphobia, specific phobia, and generalized anxiety disorder were all associated with whooping cough. The documented comorbidity was associated with increased disability and decreased quality of life.
Discussion: The detected comorbidity patterns may contribute to a better understanding of the psychobiological pathways of comorbidity. Further, increased burden of individuals affected underlines the need for studies evaluating the effect of treatment in comorbid cases.
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Zusammenfassung
Hintergrund: Angststörungen weisen eine hohe Komorbidität mit anderen psychischen Störungen auf. Dies hat wichtige Implikationen für die Belastung der Betroffenen, sowie für die Ätiologie und Therapie der komorbiden Störungen. Die Datenlage zur Komorbidität mit körperlichen Erkrankungen in der Bevölkerung ist jedoch für spezifische Angststörungen eingeschränkt. Die vorliegende Dissertation untersucht den Zusammenhang zwischen spezifischen Angststörungen und nichtübertragbaren und übertragbaren körperlichen Erkrankungen in der Bevölkerung. Weiter wird die Assoziation der Komorbidität mit Lebensqualität und Beeinträchtigung untersucht.
Methode: Analysiert wurden die Daten des Bundesgesundheitssurvey, einer repräsentativen Bevölkerungsstichprobe Deutschlands mit 4’181 Probanden im Alter von 18-65 Jahren. Angststörungen wurden mit dem DIA-X/M-CIDI Interview erhoben, nichtübertragbare körperliche Erkrankungen mit einem ärztlichen Interview, sowie mit einem Fragebogen und übertragbare körperliche Erkrankungen mit einem Fragebogen.
Resultate: Sowohl die Zwangsstörung als auch die Spezifische Phobie traten gehäuft mit Migräne und Atemwegserkrankungen auf. Auch subklinische Formen der Zwangsstörung waren mit spezifischen, nichtübertragbaren körperlichen Erkrankungen assoziiert. Agoraphobie, Spezifische Phobie und Generalisierte Angststörung gingen mit erhöhten Prävalenzraten von Keuchhusten einher. Komorbidität war mit erhöhter Beeinträchtigung und niedrigerer Lebensqualität assoziiert.
Diskussion: Die Komorbidiätsmuster können zu einem besseren Verständnis der zugrundeliegenden Mechanismen beitragen. Die assoziierte Belastung unterstreicht die Bedeutung weiterer Forschung zur Wirksamkeit der Therapie bei komorbiden Erkrankungen.
From mental-physical comorbidity to somatic symptoms - insights gained from research on symptoms of mental disorders
No full textAbstract in English
Background: Mental health and physical health are substantially associated with each other. The early recognition of co-occurring mental-physical conditions, as well as the early recognition of pathophysiological mechanisms underlying somatic symptoms, might be of special relevance for a better understanding of early phases of disorder development and hence prevention.
Aim: To examine associations between symptoms of mental disorders (depressive symptoms and gambling behavior) and physical diseases, as well as associations between somatic symptoms and sensory responsiveness.
Methods: We estimated (1) the association between depressive symptoms and physical diseases (N = 14,348), (2) the association between gambling and physical diseases (N = 11,385), and (3) the association of sensory responsiveness with somatic symptoms and illness anxiety (N = 205). Logistic regression analyses were conducted to estimate the associations in studies (1) and (2). To estimate the associations in study (3) we conducted a linear multiple regression model. We controlled for potential confounders in all three studies.
Results: (1) Depressive symptoms were associated with Arthrosis and Arthritis and any physical disease. (2) Gambling in the past 12 months was associated with Diabetes, Arthrosis and Arthritis, High blood pressure, allergies like Hay Fever, and any physical disease. (3) Increased sensory responsiveness was associated with increased scores of the overall illness anxiety scale and its constituent subscale disease conviction.
Discussion: Symptoms of mental disorders were associated with physical diseases and increased sensory responsiveness was associated with illness anxiety. Scrutinizing these associations might contribute to a better understanding of mental-physical comorbidity and might therefore have implications for early recognition, treatment and health care policy.-----------Abstract in German
Hintergrund: Psychische und körperliche Gesundheit sind stark miteinander verbunden. Die Früherkennung von gemeinsam auftretenden psychisch-körperlichen Erkrankungen, sowie somatischen Symptomen zugrundeliegenden pathophysiologischen Mechanismen, könnte zu einem besseren Verständnis der frühen Krankheitsentwicklung und somit der Prävention beitragen.
Ziel: Untersuchung der Zusammenhänge zwischen Symptomen psychischer Störungen (depressive Symptome und Glücksspielverhalten) und körperlichen Erkrankungen, sowie der Zusammenhänge zwischen somatischen Symptomen und sensorischer Empfindlichkeit.
Methode: Untersucht wurden die Assoziation zwischen (1) depressiven Symptomen und körperlichen Erkrankungen (N = 14,348), (2) Glücksspielverhalten und körperlichen Erkrankungen (N = 11,385), und (3) sensorischer Empfindlichkeit und somatischen Symptomen oder Krankheitsangst (N = 205). Assoziationen in Studie (1) und (2) wurden anhand logistischer Regressionen geschätzt. In Studie (3) wurde ein lineares multiples Regressionsmodells verwendet. Potenzielle Störvariablen wurden in allen drei Studien kontrolliert.
Resultate: (1) Depressive Symptome waren mit Arthrose und Arthritis und irgendeiner körperlichen Erkrankung assoziiert. (2) Glücksspiele spielen in den letzten 12 Monaten war mit Diabetes, Arthrose und Arthritis, hohem Blutdruck, Allergien wie Heuschnupfen und irgendeiner körperlichen Erkrankung assoziiert. (3) Erhöhte sensorische Empfindlichkeit war mit höheren Werten auf der allgemeinen Krankheitsangstskala und der Unterskala Krankheitsüberzeugung assoziiert.
Diskussion: Symptome psychischer Störungen waren assoziiert mit körperlichen Erkrankungen und erhöhte sensorische Empfindlichkeit war assoziiert mit Krankheitsangst. Die eingehende Untersuchung dieser Zusammenhänge könnte zu einem besseren Verständnis psychisch-körperlicher Komorbiditäten beitragen und somit Implikationen für die Früherkennung, Behandlung und Gesundheitspolitik haben
Applications of the network perspective in clinical psychology and psychotherapy
No full textThe complex network perspective is becoming increasingly popular in the field of clinical psychology and psychotherapy and assumes that the occurrence of a mental disorder can be characterized by the activation of a network of interrelated elements (previously termed ‘symptoms’). This perspective adopts an advanced computational method, network analysis (NA), which gives empirical data a new framework with the aim of extracting information relevant to clinical research and practice. In this thesis, we describe three applications of NA in clinical psychology and psychotherapy. First, we examined multimorbidity patterns as a function of psychopathology severity levels. We found that major mental symptom domain interrelations become consistent at and above a subthreshold level suggesting that specific patterns emerge as psychopathology severity levels increase. Second, we scrutinized how mental health (MH) service use is related to transdiagnostic symptom networks. Findings suggest that after adjusting for potential confounding by indication for service use, there was no indication of an association in overall connectivity or network structure of networks with versus without MH services use. However, selected structurally important symptoms differed consistently between networks with versus without MH service use indicating that more granular network characteristics on the node level may complement and enrich traditional outcomes in clinical research. Third, we applied dynamic NA techniques to model temporal and cross-sectional associations of symptoms and affective, cognitive, and behavioral elements in patients with Globus Sensations (GS) over the course of psychotherapy. We found that GS were not temporally associated with any affective, cognitive, and behavioral elements. We did find indications for potential causal pathways between catastrophizing cognitions and bodily weakness as well as GS and somatic distress, which may reflect temporal associations in patients with GS in the context of treatment. Our findings have several implications for clinical research and practice and further provide a theoretical basis and guidance for future research using cross-sectional and dynamical NA in the context of clinical psychology and psychotherapy
Salivary biomarkers in pregnant women : clinical outcomes and methodological aspects
No full textZusammenfassung
Ziel: Die vorliegende Dissertation untersucht (1) methodische Aspekte einer möglichst
reliablen ambulanten Erfassung von Speichel-Testosteron- und -Cortisolkonzentrationen bei
Schwangeren sowie (2) die Assoziation zwischen dem Speichel-Testosteron-Tagesrhythmus
Schwangerer und der Geburtsgröße des Nachwuchses.
Methode: In einer prospektiven Studie instruierten wir 75 Frauen, während ihrer
Schwangerschaft Speichelproben nach einem ambulanten Standard-Protokoll zu sammeln.
Wir erfassten die Adhärenz der Schwangeren bezüglich multipler vorgesehener
Messzeitpunkte für die Speichelsammlung mit einem für die Schwangeren nicht ersichtlichen
elektronischen Adhärenz-Monitoring. Ob eine Vorabinformation über dieses Monitoring
und/oder das zur Verfügung-Stellen eines Zeitmessers mit Alarmfunktion die Adhärenz
verbessert, untersuchten wir mit einem randomisierten kontrollierten Design. Wir bestimmten
die Testosteron- und Cortisolkonzentrationen im Speichel und entnahmen die Geburtsgröße
des Nachwuchses aus den Patientenakten.
Resultate: (1) Bei der Speichelsammlung kam eine Nicht-Adhärenz mit vorgesehenen
Messzeitpunkten vor und war mit verminderten Speichel-Testosteron- und -Cortisolwerten
assoziiert. Die Vorabinformation über ein Adhärenz-Monitoring, nicht aber das zur
Verfügung-Stellen eines Zeitmessers, ging mit einer verbesserten Adhärenz einher. (2) Ein
abgeflachter Testosteron-Tagesrhythmus war mit einer reduzierten Geburtsgröße assoziiert.
Diskussion: (1) Die bei einer ambulanten Speichelsammlung bei Schwangeren auftretende
Nicht-Adhärenz kann mit einem Bias bei der Speichel-Testosteron- und -Cortisolbestimmung
einhergehen. Für eine reliable Bestimmung der Konzentrationen im Speichel von
Schwangeren scheint die Berücksichtigung der Adhärenz-Problematik bedeutsam zu sein. (2)
Ein abgeflachter mütterlicher Testosteron-Tagesrhythmus während der Schwangerschaft
könnte ein neuer, potentiell relevanter Prädiktor für ein reduziertes fetales Wachstum sein.
SALIVARY BIOMARKERS IN PREGNANT WOMEN ----------Abstract
Objective: This dissertation examines in pregnant women (1) methodological aspects to
reliably assess salivary testosterone and cortisol concentrations in an ambulatory setting and
(2) the association between women’s diurnal salivary testosterone change during pregnancy
and offspring size at birth.
Methods: In a prospective study, we instructed 75 pregnant women to collect multiple saliva
samples according to a standard ambulatory saliva-sampling protocol. We assessed women’s
adherence to scheduled saliva sampling times with a hidden electronic adherence-monitoring
system. Using a randomized controlled design, we estimated whether a disclosure
intervention (informing women about the adherence monitoring) and a reminder intervention
(use of acoustical reminders) improved adherence. We assessed testosterone and cortisol
concentrations in the saliva samples and collected information on offspring size at birth from
medical birth records.
Results: (1) Overall, pregnant women indicated nonadherence with scheduled saliva sampling
times that was associated with lower salivary testosterone and cortisol concentration
estimates. The disclosure intervention, but not the reminder intervention, improved adherence
to the sampling schedule. (2) Women’s flattened diurnal testosterone change during
pregnancy was associated with reduced offspring size at birth for gestational age.
Conclusions: (1) Results suggest that in pregnant women, nonadherence to scheduled
ambulatory saliva sampling is common and associated with biased estimates of salivary
testosterone and cortisol concentrations. Therefore, it is important to address nonadherence
when utilizing ambulatory assessments of salivary testosterone and cortisol concentrations in
pregnant women. (2) Moreover, women’s flattened diurnal testosterone change during
pregnancy may be a new, potentially relevant predictor of reduced fetal growth. This finding
may contribute potentially to a better risk assessment of fetal growth restrictions
Real-time fMRI neurofeedback and smartphone-based interventions to modulate mental functions
No full textOur brains are constantly changing on a molecular level depending on the demands thrown at them by our environments, behavior, and thoughts. This neuronal plasticity allows us to voluntarily influence mental functions.
Taking conscious control over mental functions goes potentially back millenia, but it was psychotherapy since the early 20th century which moulded this concept into a concrete form to target specific mental disorders.
Mental disorders constitute a large burden on modern societies. Stress-related disorders like anxiety and depression particularly make up a large part of this burden and new ways to treat or prevent them are highly desirable, since traditional approaches are not equally helpful to every person affected.
This might be because the infrastructure is not available where the person lives, their schedules and obligations or financial means do not enable them to seek help or they simply do not respond to traditional forms of treatment.
Technological advances bring forth new potential approaches to modulate mental functions and allow using additional information to tailor an intervention better to an individual patient.
The focus of this dissertation lies on two promising approaches to cognitively intervene and modulate mental functions: real-time functional magnetic resonance imaging neurofeedback (rtfMRInf) on one hand and smartphone-based interventions (SBIs) on the other.
To investigate various aspects of both these methods in the context of stress and in relation to personalized interventions, we designed and conducted two experiments with a main rtfMRInf intervention, and also with ambulatory training of mental strategies, which participants accessed on their mobile phones.
The four publication this thesis entails, are related to this topic as follows:
The first publication focuses on rtfMRInf effects on the physiological stress response, exploring whether neurofeedback could reduce stress-related changes in brain activity and blood pressure.
The second publication focuses on rtfMRInf effects on psychological measures related to the stress response, namely on arousal and mood, based on data from self-report by the participants.
The third publication focuses on rtfMRInf methodology itself, looking at complex connectivity data between major neural networks.
Finally, the fourth publication focuses on personalized prediction of intervention success of an SBI using data from previous training days
Investigating different forms of rumination in obsessive-compulsive disorder and anger
No full textRumination has traditionally been investigated in the context of depression or sadness, but it also influences various other mental disorders or types of affect. We examined different forms of rumination in the contexts of obsessive-compulsive disorder (OCD) and anger. In the context of OCD, cross-sectional observational studies were used to analyze associations of rumination as defined in the response styles theory (RST-rumination) with OCD symptoms in 140 individuals with OCD and explore psychometric properties of the Rumination on Obsessions and Compulsions Scale (ROCS), a new measure of OCD symptom rumination and mental neutralizing (two forms of rumination), in individuals with OCD (n = 99), major depressive disorder (n = 74), or no mental disorder (n = 35). In the context of anger, 120 participants were induced to ruminate about anger in an abstract and in a concrete form in randomly allocated order, with anger, negative and positive affect measured before and after rumination. RST-rumination was positively associated with a questionnaire but not an interview measure of OCD symptoms when controlling for depression and anxiety. For the ROCS, a one-factor solution for OCD symptom rumination and a three-factor solution for mental neutralizing emerged and we present correlations indicating convergent and discriminant validity and between-groups comparisons. Abstract and concrete rumination about anger had comparable effects on affect. Regarding OCD, RTS-rumination should be examined further and possibly included in models and treatments of OCD. The ROCS has promising psychometric properties and, following further validation, may be used in research and treatment of OCD. If future studies replicate the comparable effects of abstract and concrete rumination about anger on affect in individuals with high anger and over a longer time, theory and treatments of these forms of rumination may possibly need to be amended
The Use of Smartphone-Based Interventions to Improve Mental Health
No full textMental disorders are highly prevalent and cause a high burden of disease. Even though effective treatment approaches exist, there is a large treatment gap and a substantial proportion of non-responders to traditional face-to-face psychotherapy. New treatment approaches are required. The Grand Challenges in Global Mental Health initiative called for the development of mobile and IT technologies to increase access to evidence-based care. Internet-based psychotherapeutic interventions have been found efficacious. Smartphones are widespread, ensure high availability of their users, and are equipped with technologically rich sensors. In the context of electronic Health (eHealth) and mobile Health (mHealth), the potential of smartphone-based interventions has been recognized. Due to the relative novelty and interdisciplinarity of the field, several open research questions remain. This dissertation focuses on three selected research questions on how smartphone-based interventions can be used to improve mental health. The first publication provides evidence of the applicability of smartphone-based psychotherapeutic micro-interventions evoking mood changes in a real-world setting in a non-clinical sample (N = 27; n obs. = 335 micro-intervention sessions) across 13 days; data was collected in a larger randomized trial. Based on data from the same study, in the second publication, evidence is provided for the utility of a machine learning-based random forest (RF) algorithm for the prediction of smartphone-based psychotherapeutic micro-intervention success regarding mood amelioration, based on contextual information. In publication 3, based on data from healthy participants in a randomized controlled trial (N = 132), we explored whether efficacy expectancies could be successfully induced in a smartphone-based placebo mental health intervention lasting 20 days, in the context of digital placebo effects. These findings may pave the way for future endeavors to provide personalized digital mental health interventions and to further promote the promising field of eHealth and mHealth, in line with the precision medicine approach
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