Birgit Kleim

• University of Zurich

Trauma‐focused psychotherapy aims to process intrusive memories in trauma survivors, and sleep is thought to contribute to offline memory consolidation and updating following therapy. We explored associations between posttraumatic stress disorder (PTSD) symptom severity, treatment outcomes and three sleep EEG metrics during posttherapy naps: freque...

A core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing of the traumatic event in the form of intrusive memories. Doxycycline is a matrix metalloproteinase 9 (MMP-9) inhibitor. MMP-9 is required for synaptic plasticity during long-term potentiation, which is thought to underly learning and memory. Here we examin...

A core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing of the traumatic event in the form of intrusive memories. Doxycycline is a matrix metalloproteinase 9 (MMP-9) inhibitor. MMP-9 is required for synaptic plasticity during long-term potentiation, which is thought to underly learning and memory. Here we examin...

Background Up to 30% of pregnant individuals experience high levels of stress. At the same time, 15-20% of new mothers develop postpartum depression, and 25-35% experience postpartum anxiety. Mobile applications have the potential to provide an accessible, scalable solution to these mental health challenges. However, previous evidence indicates tha...

A core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing of the traumatic event in the form of intrusive memories. Doxycycline is a matrix metalloproteinase 9 (MMP-9) inhibitor. MMP-9 is required for synaptic plasticity during long-term potentiation, which is thought to underly learning and memory. Here we examin...

Frontline caregivers, such as nurses, physicians, and intensive care personnel are at heightened risk of intrusive memories, a core symptom of posttraumatic stress disorder. Understanding these intrusions and contributing factors is crucial to protecting workers’ mental health and sustaining effective patient care. Emergency department (ED) staff (...

Background Healthcare systems worldwide, including in Switzerland, face critical challenges from staff shortages, threatening their sustainability and quality of care. Medical interns transitioning into professional roles often experience heightened stress and burnout, which are key contributors to early career attrition. It is crucial to identify...

Self-efficacy is a key construct in behavioral science affecting mental health and psychopathology. Here, we expand on previously demonstrated between-persons self-efficacy effects. We prompted 66 patients five times daily for 14 days before starting cognitive behavioral therapy (CBT) to provide avoidance, hope, and perceived psychophysiological-ar...

Targeted Memory Reactivation (TMR) during sleep benefits memory integration and consolidation. In this pre-registered study, we investigated the effects of TMR applied during non-rapid eye movement (NREM) sleep following modulation and updating of aversive autobiographical memories using imagery rescripting (ImR). During 2–5 nights postImR, 80 heal...

Recalling positive autobiographical memories has been associated with various positive psychological outcomes, including enhanced mental well-being and self-efficacy. Given the known impact of stress on cognitive functioning, we investigated how momentary stress affects the repeated recall of selected autobiographical mastery memories (e.g., memori...

Following a suicide attempt, only a third of people receive outpatient treatment. This highlights the need to rethink our approach to treatment, to include the consideration of low-threshold brief interventions and contacts. Therefore, in this study, we investigated the extent to which such brief interventions and contacts (BICs) are effective. Pub...

Background: While growing research confirms the efficacy of transdiagnostic cognitive behavioral psychotherapy (TD-CBT) by examining group-level changes from pre to post-treatment, less is known about inter-individual differences and dynamic changes during therapy. Understanding different symptom trajectories and their associations with treatment o...

Objective Self-efficacy is associated with positive mental health outcomes. We developed and tested a digital self-efficacy training for daily recall of autobiographical self-efficacy memories (e.g., memories of successfully overcoming a personal challenge). Method In this randomized controlled trial, we investigated the effects of the week-long d...

Background Up to 30% of pregnant individuals experience high levels of stress. At the same time, 15-20% of new mothers develop postpartum depression, and 25-35% experience postpartum anxiety. Mobile applications have the potential to provide an accessible, scalable solution to these mental health challenges. However, previous evidence indicates tha...

Background Up to 30% of pregnant individuals experience high levels of stress. At the same time, 15-20% of new mothers develop postpartum depression, and 25-35% experience postpartum anxiety. Mobile applications have the potential to provide an accessible, scalable solution to these mental health challenges. However, previous evidence indicates tha...

Background: Stress-related disorders present a significant global burden. There is great need for effective, preventive measures. Mobile just-in-time adaptive interventions (JITAI) have the potential to be applied in real time and context-specifically, precisely when individuals need them most. However, they have not been widely implemented in the...

Objective: This pilot case series investigated the feasibility and efficacy of an eight-week therapy program, combining nasally administered ketamine (0.5 mg/kg) with trauma-focused psychotherapy, for individuals with chronic, treatment-resistant post-traumatic stress disorder (PTSD). Method: Three patients with chronic, treatment-resistant PTSD un...

Greater loneliness as well as a lack of social connectedness have often been associated with poorer sleep. However, the temporal dynamics and direction of these associations remain unclear. Aim of the current study was to examine bi-directional associations between loneliness/social connectedness and sleep in 48 stress-exposed medical students duri...

This study investigates the role of positive cognitive reappraisal (PCR) flexibility and variability in mental health in response to real-life stressors among college students. We employed ecological momentary assessment and intervention through ReApp, a mobile app designed to train and promote PCR. We analyzed data from the intervention groups acr...

Introduction Perceived responsiveness, or the extent to which one feels understood, validated and cared for by close others, plays a crucial role in people's well-being. Can this interpersonal process also protect people at risk? We assessed whether fluctuations in suicidal ideation were associated with fluctuations in the degree of perceived resp...

Background: Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing...

Objective Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined tim...

Appraisal refers to the evaluation of stimuli or situations with respect to an individual’s goals and needs. Stimuli or situations that are appraised as a threat to one’ goals and needs (‘stressors’) induce stress responses (‘stress’). Stressor appraisal occurs on various dimensions, of which the magnitude or cost of a potential adverse outcome, th...

Rationale Previous work identified an attenuating effect of the matrix metalloproteinase (MMP) inhibitor doxycycline on fear memory consolidation. This may present a new mechanistic approach for the prevention of trauma-related disorders. However, so far, this has only been unambiguously demonstrated in a cued delay fear conditioning paradigm, in w...

Pavlovian fear conditioning is widely used as a pre-clinical model to investigate methods for prevention and treatment of anxiety and stress-related disorders. In this model, fear memory consolidation is thought to require synaptic remodeling, which is induced by signaling cascades involving matrix metalloproteinase 9 (MMP-9). Here we investigated...

Transdiagnostic cognitive behavioural psychotherapy (TD-CBT) may facilitate the treatment of emotional disorders. Here we investigate short- and long-term efficacy of TD-CBT for emotional disorders in individual, group and internet-based settings in randomized controlled trials (PROSPERO CRD42019141512). Two independent reviewers screened results f...

Background There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic “ayahuasca” for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspire...

Background The mobile Agnew Relationship Measure (mARM) is a self-report questionnaire for the evaluation of digital mental health interventions and their interactions with users. With the global increase in digital mental health intervention research, translated measures are required to conduct research with local populations. Objective The aim o...

Robust reward sensitivity may help preserve mental well‐being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, “Imager,” which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two‐arm randomized co...

Background Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low “stressor reactivity” [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. Objective Extending these findings, we here examined prosp...

Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions, but optimizing their efficacy while minimizing participant burden remains a key challenge. Here, we investigated the potential benefits of a burst delivery design, i.e., intervention delivered only in pre-defined time intervals,...

Greater loneliness has often been associated with poorer sleep. However, the temporal dynamics and direction of this association remain unclear. Aim of the current study was to examine bi-directional associations between loneliness and sleep in the daily life of 50 stress-exposed medical students during their first medical internship, a period of h...

Background Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience – interventional multicenter...

Objective: Electroencephalogram (EEG) based frequency measures within the alpha frequency range (AFR), including functional connectivity, show potential in assessing the underlying pathophysiology of depression and suicide-related outcomes. We assessed the association between AFR connectivity, suicidal thoughts and behaviors, and depression in a tr...

Background: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychol...

Background: Depression remains a global health problem, with its prevalence rising worldwide. Digital biomarkers are increasingly investigated to initiate and tailor scalable interventions targeting depression. Due to the steady influx of new cases, focusing on treatment alone will not suffice; academics and practitioners need to focus on the preve...

Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treat...

The diagnostic assessment of autism spectrum disorders (ASD) in adults is a challenging and time-consuming procedure. In order to address the lack of specialised health-care professionals and improve the waiting time, we aimed to identify specific electrocardiogram (ECG) derived Heart Rate Variability (HRV) parameters that could be used for diagnos...

**Background.** Brief interventions and contacts (BICs) for suicidal thoughts and behaviors (STBs) are characterized by short treatment duration, low costs, and easy delivery. As BICs have shown promise in preventing STB [@Doupnik2020], a detailed assessment across different populations and settings is warranted. Here, we systematically reviewed th...

Background Positive prospective mental imagery plays an important role in mental well-being, and depressive symptoms have been associated with difficulties in generating positive prospective mental images (PPMIs). We used a mobile app to gather PPMIs generated by young adults during the COVID-19 pandemic and analyzed content, characteristics, and a...

Introduction: Reappraisal is one of the highly modifiable resilience factors and an important emotion regulation strategy. Reappraisal training can be delivered via mobile apps; however, such apps have typically combined reappraisal with other techniques. To address this gap, we developed ReApp, which engages users solely in reappraisal. Methods: F...

Transdiagnostic cognitive-behavioral psychotherapy (TD-CBT) may facilitate treatment of emotional disorders. We investigate short- and long-term efficacy of TD-CBT for emotional disorders in individual, group, and Internet-based settings in randomized controlled trials (PROSPERO CRD42019141512). Two independent reviewers screened results from PubMe...

BACKGROUND Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low “stressor reactivity” [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. OBJECTIVE Extending these findings, we here examined prosp...

Learning to predict threat is of adaptive importance, but aversive memory can also become disadvantageous and burdensome in clinical conditions such as posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a laboratory model of aversive memory and thought to rely on structural synaptic reconfiguration involving matrix metalloproteina...

BACKGROUND Digital tools such as Ecological Momentary Assessments (EMA) make it possible to assess transient mental health states and their parameters. Ecological Momentary Interventions (EMI) offer mental health interventions that fit well into individuals’ daily lives and routines. OBJECTIVE The aim of our study was twofold. First, to determine...

Background Digital tools assessing momentary parameters and offering interventions in people’s daily lives play an increasingly important role in mental health research and treatment. Ecological momentary assessment (EMA) makes it possible to assess transient mental health states and their parameters. Ecological momentary interventions (EMIs) offer...

Background: The core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing in form of intrusive memories. While a great number of biological processes are regulated by sleep and internal biological clocks, the effect of 24-hour biological cycles, named circadian rhythm, has not been investigated in the context of in...

Background Trauma- and stress-related disorders, such as post-traumatic stress disorder (PTSD), are more common in females than in males. Sex hormones affect learning and emotional memory formation and may be associated with the development of PTSD. Most previous studies have indexed these hormones in isolation. Objectives: To investigate associati...

Introduction: How patients respond to their depressive symptoms plays a critical role in the persistence of depression and their quality of life, as patients tend to ruminate about their symptoms. There is evidence that a self-compassionate attitude may disrupt the ruminative thinking process. Therefore, the present study tested the hypotheses that...

Perceived responsiveness, or the extent to which one feels understood, validated, and cared for by close others, has shown to play a crucial role in people's health and well-being. Can this specific interpersonal process also play a protective role in suicidal ideation for people at risk? We assessed if fluctuations in suicidal ideation were associ...

Suicidal behavior is influenced by a multitude of factors, making prediction and prevention of suicide attempts a challenge. A useful tool to uncover underlying pathophysiology or propose new therapy approaches are biomarkers, especially within the context of point-of-care tests Heart rate variability (HRV) is a well-established biomarker of mental...

BACKGROUND Blended psychotherapy (bPT) augments face-to-face psychotherapy with digital intervention components to improve effectiveness and cost-effectiveness of mental health treatment. Feasibility and effectiveness of bPT have been shown for various mental health problems, but mostly for patient groups with higher levels of functioning. OBJECTI...

Background Blended psychotherapy (bPT) combines face-to-face psychotherapy with digital interventions to enhance the effectiveness of mental health treatment. The feasibility and effectiveness of bPT have been demonstrated for various mental health issues, although primarily for patients with higher levels of functioning. Objective This scoping re...

Background: A negative self-concept is characterised by dysfunctional cognitions about the self and has been suggested to be a key factor involved in the development and maintenance of posttraumatic stress disorder (PTSD). In addition, the current definitions of PTSD according to DSM-5 and the new ICD-11 diagnosis of Complex PTSD (CPTSD) include as...

Background: The mobile Agnew Relationship Measure (mARM) is a self-report questionnaire for theevaluation of digital mental health interventions and their interactions with users. With theglobal increase in digital mental health intervention research, translated measures are requiredto conduct research with local populations.Objective: The aim of t...

BACKGROUND The mobile Agnew Relationship Measure (mARM) is a self-report questionnaire for the evaluation of digital mental health interventions and their interactions with users. With the global increase in digital mental health intervention research, translated measures are required to conduct research with local populations. OBJECTIVE The aim o...

Background: Network analysis has gained increasing attention as a new framework to study complex associations between symptoms of post-traumatic stress disorder (PTSD). A number of studies have been published to investigate symptom networks on different sets of symptoms in different populations, and the findings have been inconsistent. Objective: W...

Background Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing...

The chapter reviews the contribution of information processing models to understanding the development and maintenance of posttraumatic stress disorder (PTSD). Individual differences in cognitive processing during the trauma and basic memory mechanisms, such as priming and associative learning, may help explain why people with PTSD involuntarily re...

**Background.** Suicidal ideations (SI) are amongst the strongest predictors for suicide attempts, yet reliable prediction models for suicide risk are still lacking. One explanation for this is that endorsement and expression of SI are not uniform and may vary when indexed over time. Using intensive longitudinal assessments of SI with ecological mo...

BACKGROUND Stress-related mental disorders are highly prevalent and pose a significant burden on individuals and society. Improving strategies of their treatment and prevention requires knowledge about risk and resilience. This multi-center study aims to contribute to this endeavor by investigating psychological resilience in healthy, but vulnerabl...

Background Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psycholo...

Recently, cross-sectional relationships between psycho-social resilience factors (RFs) and resilience, operationalized as an outcome of low reactivity of mental health to stressor exposure (low ‘stressor reactivity’) during the first wave of the COVID-19 pandemic, were reported. Extending these findings, we here examine prospective relationships an...

Recently, cross-sectional relationships between psycho-social resilience factors (RFs) and resilience, operationalized as an outcome of low reactivity of mental health to stressor exposure (low ‘stressor reactivity’) during the first wave of the COVID-19 pandemic, were reported. Extending these findings, we here examine prospective relationships an...

Language is a potential source of predictors for suicidal thoughts and behaviors (STBs), as changes in speech characteristics, communication habits, and word choice may be indicative of increased suicide risk. We reviewed the current literature on STBs that investigated linguistic features of spoken and written language. Specifically, we performed...

Background: Positive prospective mental imagery plays an important role in mental well-being, and depressive symptoms have been associated with difficulties in generating positive prospective mental images (PPMIs). We used a mobile app to gather PPMIs generated by young adults during the COVID-19 pandemic and analyzed content, characteristics, and...

A considerable number of depressed patients do not respond to treatment. Accurate prediction of non-response to routine clinical care may help in treatment planning and improve results. A longitudinal sample of N = 239 depressed patients was assessed at admission to multi-modal day clinic treatment, after six weeks, and at discharge. First, patient...

Background: Self-efficacy is associated with positive mental health outcomes. We developed and tested a digital self-efficacy training involving repeated recall of autobiographical self-efficacy memories.Methods: In this randomized controlled trial, we investigated the effects of our digital training on key mental health outcomes, including anxiety...

Aversive autobiographical memories play a key role in the development and maintenance of many mental disorders. Imagery rescripting is a well-established psychotherapeutic intervention aiming to create a more adaptive version of an aversive memory by modifying its interpretation. Sleep has been shown to support reconsolidation of updated neutral me...

Background: This paper describes the study protocol for our clinical trial “Optimizing Outcomes in Psychotherapy for Anxiety Disorders (OPTIMAX)” funded by the Swiss National Science Foundation (10001C_169827). The study aims to establish predictive features for forecasting response to cognitive behavior therapy (CBT) and to investigate mechanisms...

The locus coeruleus (LC) is a brainstem structure that sends widespread efferent projections throughout the mammalian brain. The LC constitutes the major source of noradrenaline (NE), a modulatory neurotransmitter that is crucial for fundamental brain functions such as arousal, attention, and cognitive control. This role of the LC-NE is traditional...

Introduction: Robust sensitivity to reward may help preserve positive emotions in the face of adversity and has been proposed as a key resilience factor. We describe the development, feasibility, and efficacy of an mHealth application, Imager, which targets reward sensitivity by training individuals to create mental images of future rewarding exper...

Stress-related mental disorders are highly prevalent and pose a significant burden on individuals and society. Improving strategies of their treatment and prevention requires knowledge about risk and resilience. This multi-center study aims to contribute to this endeavor by investigating psychological resilience in healthy, but vulnerable young adu...

Background There is a substantial burden on global mental health as a result of the Coronavirus disease 2019 (COVID-19) pandemic that has become putting pressure on healthcare systems. There is increasing concern about rising suicidality consequential to the COVID-19 pandemic and the measures taken. Existing research about the impact of earlier epi...

Medical personnel working in emergency rooms (ER) are at increased risk of mental health problems and suicidality. There is increasing evidence that mindfulness-based interventions can improve burnout and other mental health outcomes in health care providers. In contrast, few longitudinal prospective studies have examined protective functions of di...

[This corrects the article DOI: 10.3389/fpubh.2021.625640.].

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals' health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, indi...

Background: Multi-sensor fitness trackers offer the perspective to longitudinally estimate sleep quality in a home environment with the potential to outperform traditional actigraphy. To benefit from these new tools to objectively assess sleep for clinical and research purposes, multi-sensor wearable devices require careful validation against the g...

Background: There is an increasing number of smartphone applications (apps) focusing on prevention, treatment, and diagnosis of depression. A promising approach to increase the effectiveness while reducing the individual's burden is the use of just-in-time adaptive intervention (JITAI) mechanisms. JITAIs are designed to improve the effectiveness o...

Reappraisal of negative memories and experiences is central for mental health and well-being. Deficiency of reappraisal lies at the core of many psychiatric disorders and is a key target for treatment. Here we apply transcranial direct current stimulation (tDCS) to enhance reappraisal of negative emotional memories. In a randomised, sham-controlled...

Each year, more than 800,000 persons die by suicide, making it a leading cause of death worldwide. Recent innovations in information and communication technology may offer new opportunities in suicide prevention in individuals, hereby potentially reducing this number. In our project, we design digital indices based on both self-reports and passive...

Several types of psychological treatment for posttraumatic stress disorder (PTSD) are considered well established and effective, but evidence of their long-term efficacy is limited. This systematic review and meta-analysis aimed to investigate the long-term outcomes across psychological treatments for PTSD. MEDLINE, Cochrane Library, PTSDpubs, Psyc...