DNA methylation of FKBP5 and response to exposure-based psychological therapy

Differential DNA methylation of the HPA-axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences, and may play a role in how well people respond to psychological treatments. Participants (n=111) received exposure-based CBT for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (β=-4.26, p=3.90x10-4), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p=0.045), but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences

Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders

Objectives: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Methods: Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. Results: Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. Conclusions: We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations

Guided Practice in behavioral therapy

Patientenübungen, die außerhalb des Therapieraums stattfinden und vom Therapeuten angeleitet werden, sind häufige Bestandteile kognitiv-verhaltenstherapeutischer Behandlungen. Auch wenn Guided-Practice (GP-)Übungen für viele Verhaltenstherapeuten eine Selbstverständlichkeit darstellen, gibt es bei der Planung und Umsetzung solcher Übungen Vorbehalte, die unter anderem ethische und empirische Aspekte umfassen. Der folgende Beitrag gibt zu­nächst praktische Hinweise zur Gestaltung von GP-Übungen, bevor im Anschluss die aktuelle Evidenzlage in Bezug auf therapeutenbegleitete Übungen außerhalb des Thera­pieraums skizziert und potentielle Nebenwirkungen der Me thode diskutiert werden.Therapist-guided exercises that take place outside the therapy room are common components of cognitive-behavioral therapies. Although guided practice exercises are a matter of course for many behavioral therapists, reservations regarding guided practice exercises are common and include ethical as well as empirical aspects. The following article gives practical hints for the design of guided practice exercises. Furthermore, the current evidence regarding therapist-guided exercises is summarized and potential side effects of the method are discussed

High place phenomenon: prevalence and clinical correlates in two German samples

Background: The high place phenomenon, that is, a sudden urge to jump when in a high place, is an experience known to many people, that has rarely been studied. The present study aimed to assess the prevalence of the high place phenomenon in a non-clinical and a clinical German sample. Furthermore, clinical correlates of the experience were assessed. Methods: The study sample comprised 276 participants (67% female; Mage = 32.08, SDage = 10.73) who took part in an online assessment and 94 patients (73.4% female; Mage = 49.26, SDage = 13.32) suffering from clinically relevant fear of flying. Participants filled out questionnaires on experiences with the high place phenomenon, depression, anxiety, suicide ideation and anxiety sensitivity. Results: The high place phenomenon was known to nearly 60% of the online sample and to 45% of the patient sample. Suicide ideation as well as anxiety sensitivity were positively associated with experiences with the high place phenomenon in the online sample. Depression, anxiety and suicide ideation were unrelated to experiences with the phenomenon in the patient sample. Conclusion: The high place phenomenon is commonly reported by (lifetime/current) suicide ideators. However, it is also a common experience in individuals who have never suffered from suicide ideation. It is therefore cautioned not to interpret such experiences as an expression of a hidden death wish

Lifestyle choices and mental health: a longitudinal survey with German and Chinese students

Abstract Background A healthy lifestyle can be beneficial for one’s mental health. Thus, identifying healthy lifestyle choices that promote psychological well-being and reduce mental problems is useful to prevent mental disorders. The aim of this longitudinal study was to evaluate the predictive values of a broad range of lifestyle choices for positive mental health (PMH) and mental health problems (MHP) in German and Chinese students. Method Data were assessed at baseline and at 1-year follow-up. Samples included 2991 German (M age = 21.69, SD = 4.07) and 12,405 Chinese (M age = 20.59, SD = 1.58) university students. Lifestyle choices were body mass index, frequency of physical and mental activities, frequency of alcohol consumption, smoking, vegetarian diet, and social rhythm irregularity. PMH and MHP were measured with the Positive Mental Health Scale and a 21-item version of the Depression Anxiety and Stress Scale. The predictive values of lifestyle choices for PMH and MHP at baseline and follow-up were assessed with single-group and multi-group path analyses. Results Better mental health (higher PMH and fewer MHP) at baseline was predicted by a lower body mass index, a higher frequency of physical and mental activities, non-smoking, a non-vegetarian diet, and a more regular social rhythm. When controlling for baseline mental health, age, and gender, physical activity was a positive predictor of PMH, smoking was a positive predictor of MHP, and a more irregular social rhythm was a positive predictor of PMH and a negative predictor of MHP at follow-up. The good fit of a multi-group model indicated that most lifestyle choices predict mental health comparably across samples. Some country-specific effects emerged: frequency of alcohol consumption, for example, predicted better mental health in German and poorer mental health in Chinese students. Conclusions Our findings underline the importance of healthy lifestyle choices for improved psychological well-being and fewer mental health difficulties. Effects of lifestyle on mental health are comparable in German and Chinese students. Some healthy lifestyle choices (i.e., more frequent physical activity, non-smoking, regular social rhythm) are related to improvements in mental health over a 1-year period

High place phenomenon

$\bf Background$ The high place phenomenon, that is, a sudden urge to jump when in a high place, is an experience known to many people, that has rarely been studied. The present study aimed to assess the prevalence of the high place phenomenon in a non-clinical and a clinical German sample. Furthermore, clinical correlates of the experience were assessed. $\bf Methods$ The study sample comprised 276 participants (67% female; Mage = 32.08, SDage = 10.73) who took part in an online assessment and 94 patients (73.4% female; Mage = 49.26, SDage = 13.32) suffering from clinically relevant fear of flying. Participants filled out questionnaires on experiences with the high place phenomenon, depression, anxiety, suicide ideation and anxiety sensitivity. $\bf Results$ The high place phenomenon was known to nearly 60% of the online sample and to 45% of the patient sample. Suicide ideation as well as anxiety sensitivity were positively associated with experiences with the high place phenomenon in the online sample. Depression, anxiety and suicide ideation were unrelated to experiences with the phenomenon in the patient sample. $\bf Conclusion$ The high place phenomenon is commonly reported by (lifetime/current) suicide ideators. However, it is also a common experience in individuals who have never suffered from suicide ideation. It is therefore cautioned not to interpret such experiences as an expression of a hidden death wish

Lifestyle choices and mental health

$\bf Background:$ A healthy lifestyle can be beneficial for one’s mental health. Thus, identifying healthy lifestyle choices that promote psychological well-being and reduce mental problems is useful to prevent mental disorders. The aim of this longitudinal study was to evaluate the predictive values of a broad range of lifestyle choices for positive mental health (PMH) and mental health problems (MHP) in German and Chinese students. $\bf Method:$ Data were assessed at baseline and at 1-year follow-up. Samples included 2991 German ($M_{age}$ = 21.69, SD=4.07) and 12,405 Chinese (($M_{age}$=20.59, SD = 1.58) university students. Lifestyle choices were body mass index, frequency of physical and mental activities, frequency of alcohol consumption, smoking, vegetarian diet, and social rhythm irregularity. PMH and MHP were measured with the Positive Mental Health Scale and a 21-item version of the Depression Anxiety and Stress Scale. The predictive values of lifestyle choices for PMH and MHP at baseline and follow-up were assessed with single-group and multi-group path analyses. $\bf Results:$ Better mental health (higher PMH and fewer MHP) at baseline was predicted by a lower body mass index, a higher frequency of physical and mental activities, non-smoking, a non-vegetarian diet, and a more regular social rhythm. When controlling for baseline mental health, age, and gender, physical activity was a positive predictor of PMH, smoking was a positive predictor of MHP, and a more irregular social rhythm was a positive predictor of PMH and a negative predictor of MHP at follow-up. The good fit of a multi-group model indicated that most lifestyle choices predict mental health comparably across samples. Some country-specific effects emerged: frequency of alcohol consumption, for example, predicted better mental health in German and poorer mental health in Chinese students. $\bf Conclusions:$ Our findings underline the importance of healthy lifestyle choices for improved psychological well-being and fewer mental health difficulties. Effects of lifestyle on mental health are comparable in German and Chinese students. Some healthy lifestyle choices (i.e., more frequent physical activity, non-smoking, regular social rhythm) are related to improvements in mental health over a 1-year period

Modality of fear cues affects acoustic startle potentiation but not heart-rate response in patients with dental phobia

The acoustic startle response (SR) has consistently been shown to be enhanced by fear-arousing cross-modal background stimuli in phobics. Intra-modal fear-potentiation of acoustic SR was rarely investigated and generated inconsistent results. The present study compared the acoustic SR to phobia-related sounds with that to phobia-related pictures in 104 dental phobic patients and 22 controls. Acoustic background stimuli were dental treatment noises and birdsong and visual stimuli were dental treatment and neutral control pictures. Background stimuli were presented for 4 s, randomly followed by the administration of the startle stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials. Irrespective of their content, background pictures elicited greater SR than noises in both groups with a trend for phobic participants to show startle potentiation to phobia-related pictures but not noises. Unlike controls, phobics showed HR acceleration to both dental pictures and noises. HR acceleration of the phobia group was significantly positively correlated with SR in the noise condition only. The acoustic SR to phobia-related noises is likely to be inhibited by prolonged sensorimotor gating

Genetik und Epigenetik in der Psychotherapie von Depression und Angststörungen

Obwohl heute für die meisten psychischen Störungen über die gesamte Lebensspanne hinweg wirksame psychotherapeutische Behandlungsangebote zur Verfügung stehen, besteht immer noch eine zu große Variabilität in Bezug auf den kurz- und langfristigen Erfolg solcher Interventionen. Das Feld der Therapiegenetik beschäftigt sich mit der Vorhersage des Erfolges psychotherapeutischer Behandlungen durch genetische oder epigenetische Marker. Dabei wird das Ziel verfolgt, zukünftig psychotherapeutische Interventionen auf der Basis solcher Marker individualisiert anzuwenden und dadurch die Effektivität der Behandlungsangebote weiter zu verbessern. In diesem Beitrag wird der aktuelle Stand der Forschung in diesem Feld dargestellt, methodologische Herausforderungen skizziert und die Entwicklung der noch jungen Disziplin, ausgehend von theoriegeleiteten Kandidatengenstudien, hin zu hypothesenfreien genomweiten Assoziationsstudien und der Verwendung polygener Risiko-Scores, nachgezeichnet. Der zweite Abschnitt dieses Übersichtsartikels widmet sich epigenetischen Prozessen und diskutiert kritisch erste Befunde, die sich mit Modifikation von DNA-Methylierungsmustern im Zuge psychotherapeutischer Intervention beschäftigen.Although effective psychotherapeutic treatment is now available for most mental disorders throughout the life span, there is still large variability in the short and long-term success of such interventions. The field of therapygenetics is concerned with predicting the success of psychotherapeutic treatments using genetic or epigenetic markers. The long-term goal is to individualize future psychotherapeutic interventions on the basis of such markers to further improve the effectiveness of treatment options. In this review, we present the current state of research, outline methodological challenges, and trace the development of this still young discipline from theory-based candidate gene studies to hypothesis-free genome-wide association studies. In the second part of this review, epigenetic processes are discussed, with a focus on recent studies investigating intervention-associated modifications of DNA methylation patterns