Research Foci of the Research Training Group

Adversive Childhood Experience (ACE) can have long-lasting adverse effects on the brain and other somatic systems, specifically through epigenetic mechanisms and influences on brain development. In adulthood, the prior experience of ACE can result in complex clinical profiles with several co-occurring mental and somatic disorders. The risk for developing a mental disorder after ACE is highest for major depression disorder (MDD), posttraumatic stress disorder (PTSD), borderline personality disorder (BPD), and substance-use disorder (SUD). Furthermore, psychological and psychosocial mechanisms known to contribute to mental disorders are affected after ACE, such as impairments in cognitive and affective processing, including social emotions such as heightened experience of loneliness, as well as social cognitive functioning and social interactions, including aggressive behaviours. Furthermore, emerging evidence suggests that ACE promote the development of obesity, diabetes and other non-communicable as well as inflammatory diseases. Somatic symptom disorder (SSD), including abnormal pain perception with and without corresponding somatic pathology (e.g., chronic pain vs. pain during child birth) has shown to be enhanced after ACE.

Taken together, there is an urgent need to study complex ACE-related characteristics and mechanisms relevant for mental and somatic disorders by integrating state-of-the-art knowledge and methods. Identifying and validating psychosocial and somatic risk factors and diagnostic markers shall result in the development of innovative somatic and psychological treatment options for patients suffering from ACE-related disorders.


Research Focus A: ACE Characteristics

These projects focus on factors contributing to elevated risk or resilience with respect to the development of mental and somatic disorders after ACE, particularly regarding type, timing, and intensity of ACE. The influence of these factors on alterations in human brain morphometry will be studied in project A1. The influence of type, timing and intensity will be studied in an animal model (A2), which will also be used in project C4. Within the RTG, we will be able to combine data from several existing samples of affected individuals: data from a recently started prospective study on refugee children (A3) as well as an ongoing large-scale prospective community study (A4). The RTG duration of maximal nine years will give the opportunity to cover critical developmental periods and allow consecutive follow-up investigations, which will give rise to various new projects.

Brain Morphometry (A1)

Type and Timing of ACE and Brain Morphological Alterations

ACE have been postulated to be associated with morphological alterations of the brain. First evidence hints at certain vulnerable periods in which traumatisation is associated with damage of regions such as hippocampus and amygdala. However, these studies need to be replicated in larger samples. Furthermore, the influence of specific types as well as the timing of ACE needs to be investigated. The planned doctoral projects will tackle these questions and also look at neuropsychological deficits related to these morphological alterations.

Principal Investigators: C. Schmahl, G. Ende

PhD Student: Claudius von Schröder

Neurobiology (A2)

The Impact of Early Social Adversity on Social and Emotional Competence in Later Life and the Underlying Neurobiological Mechanisms

This project studies consequences of early social adversity (ESA) on social competence and emotional behaviour throughout lifetime in rats. Longitudinal studies in rats allow to systematically examine (i) the underlying neurobiological mechanisms of effects of ESA and (ii) its mediators such as ESA type, timing, intensity, and gender. The planned PhD projects will obtain a causal mechanistic understanding of the molecular underpinnings of the pathological behavioural consequences of ESA. Different techniques from longitudinal behavioural analysis in the social and emotional domains to neuroanatomical techniques, and the use of virus-mediated gene transfer and novel transgenic rat models will be applied.

Principal Investigators: R. Spanagel, A.C. Hansson

PhD Student: Akseli Surakka

Risk Factors (A3)

Risk Factors and Vulnerable Time Periods for Development and Mental Health in Refugee Children and Adolescents

War-related violence and flight are particularly severe ACE. To date, research on resilience-supporting factors in the receiving social environment (host community) is confined to observational studies. The arrival of a large quantity of refugee children over a very short time in Germany (10-2015 to 3-2016) and the subsequent distribution of children to differing communities offers a unique opportunity for doctoral projects to evaluate heterogeneous communities or neighbourhood factors and their interaction with resilience-supporting family factors, individual exposure to trauma on the long-term developmental and mental health trajectory in refugee children aged 5-14 years.

Principal Investigators: J. E. Fischer, J. Lindert

PhD Student: Shaymaa Abdelhamid

Resilience Factors (A4)

Resilience Factors in the Mannheim Study of Children at Risk

ACE have been linked to a broad range of psychiatric disorders from both the externalizing and the internalizing spectrum. So far, however, it is unclear why some individuals develop a disorder while others continue to demonstrate psychobiological allostasis. In this context, it has been suggested that protective factors may play an important role in counteracting ACE. The planned doctoral projects will engage in this topic by elucidating resilience from a multilevel perspective, i.e., taking (social) environmental, genetic, personality, hormonal, and neural factors into account.

Principal Investigators: T. Banaschewski, N. Holz

PhD Student: Eline Kraaijenvanger


Research Focus B: Psychosocial Consequences

Due to the fact that ACE frequently involve interpersonal acts, these projects focus largely on conditions relevant for social functioning, namely emotion processing (B1), social environment (B2), social emotions such as loneliness (B3) and aggression (B4). Besides, frequent ACE-related psychopathology such as SUD (B5) is of interest, as well as MDD (see also C1, C2), PTSD, and SSD (C1). In these projects, psychophysiological, neuroendocrinological, neuroimaging or ambulatory assessment methods will be used to clarify the role of ACE in the development of psychosocial consequences and disease-related mechanisms.

Emotion Processing (B1)

Emotion Processing in Individuals with ACE - a Daily Life Study

ACE were found to be related to deficits in emotion processing and interpersonal problems in later life. However, the connection between aversive emotional states, biased emotion recognition and interpersonal problems remains unexplored in the daily lives of patients. Likewise, the influence of possible moderators, such as intrusions and dissociative symptoms remains unknown. Consequently, the proposed doctoral projects aim to elucidate the link between emotion dysregulation and interpersonal problems in the daily lives of individuals with a history of ACE.

Principal Investigator: I. Niedtfeld

PhD Student: Sarah Schmitz

Social Environment (B2)

ACE and Stress Sensitivity: the Modulatory Role of the Social Environment 

ACE have enduring effects on human stress regulatory circuits and promotes alterations in stress sensitivity and emotion regulation in later life. The likelihood of the sensitized neural system to (de)compensate is thereby shaped by adverse and protective social influences in everyday life, but the examination is methodologically challenging. The planned doctoral projects will tackle this problem and interrogate data on prior ACE, alterations in stress sensitivity and emotion regulation and real-life social environmental exposures to identify the intermediate neural mechanisms.

Principal Investigators: H. Tost, A. Meyer-Lindenberg

PhD Student: Oksana Berhe

Loneliness (B3)

Loneliness, Social Belonging and ACE: Determinants and Treatment

Chronic and pervasive loneliness, i.e., a lack in the sense of social belonging and social affiliation, has been identified as an important factor in the relation between ACE and mental disorders. ACE have also been linked to somatic disorders, however, the mediating role of loneliness to the development of somatic disorders has not been investigated. The planned doctoral projects will aim at investigating a) the link between ACE, loneliness, and mental and somatic diseases, b) the mechanisms underlying the detrimental effects of loneliness after ACE and they will c) develop and evaluate psychosocial interventions that aim to improve the experiential and behavioural aspects of loneliness and social isolation.

Principal Investigators: M. Bohus, S. Lis

PhD Student: Ezgi Erol

Aggression (B4)

The Relationship of ACE and Violent Video Gaming: Effects on Pain Perception, Pain-Related Empathy and Aggression Towards Self and Others

There is initial behavioural evidence that violent video gaming leads to reduced pain perception and reduced empathy for pain as well as enhanced aggression towards self and others. ACE appear to be a central moderator in these effects. The planned doctoral projects will examine how violent video gaming is associated with childhood adversity and stress and will analyse the not yet well understood underlying psychobiological mechanisms.

Principal Investigators: H. Flor, S. Becker

PhD Student: Maxi Luisa Ritter

Addiction (B5)

Stress sensitivity, emotion processing and cue-reactivity in substance-related disorders: the influence of ACE

ACE are related to the development of SUD and behavioural addictions. Further knowledge on the interaction of behavioural, neural and physiological risk factors would be helpful for treatment and prevention of addictive disorders. The suggested doctoral projects will examine stress sensitivity, emotion processing and cue-reactivity using fMRI in alcohol use disorder (AUD) with and without ACE.

Principal Investigators: F. Kiefer, S. Vollstädt-Klein

PhD Student: Sarah Gerhardt


Research Focus C: Somatic Consequences

Research Focus B blends into C, in consideration of the interface of somatic and psychiatric symptomatology (C1). Since ACE increase the vulnerability for several frequent somatic disorders or conditions, this research focus involves mechanisms of diabetes (C2), inflammatory bowel diseases (C3), and chronic pain (C4). ACE may also affect the experience of regular somatic conditions, such as child birth and labor (C5). Projects with main research focus C will retrospectively assess ACE and are interested in somatic and neurobiological, but also psychosocial markers. One study also uses an animal model to examine the consequences of ACE-related alterations experimentally in a controlled environment (C4). Research focus B and C will make use of a central recruitment of study participants, which has been successfully established in KFO 256.

Comorbidities (C1)

Shared and Diagnosis-Specific Alterations of Functional Domains in Highly Comorbid Psychiatric Disorders Related to ACE

Adult patients with an ACE history show particularly high degrees of comorbidity of psychiatric disorders. The planned doctoral projects will investigate psychological and brain mechanisms that identify the negative functional impacts of ACE in MDD, PTSD, and somatic symptom disorder (SSD), i.e., disorders with particularly high prevalence in the sequelae of ACE and high comorbidities among each other. The aim is the identification of ACE-related shared and distinct alterations of functional domains across diagnostic groups. The role of type and intensity of ACE in the emergence of specific mental disorders and the mechanisms affected will be examined.

Principal Investigators: S.C. Herpertz, K. Bertsch

PhD Student: Katja Seitz

Obesity & Diabetes (C2)

Childhood Escape – Late Life Risk for Obesity and Diabetes

The planned doctoral projects will examine the association between childhood escape from East Prussia in World War II (WW II) and late-life health-related outcomes. Since ACE have been related to an increased risk for obesity, diabetes mellitus type 2 (DM2), MDD, and dysregulation of the HPA system, we will study the prevalence of these phenotypes in elderly participants who experienced ACE, either individually (WW II East Prussia refugees) or trans-generationally (mother was WW II refugee). Since the effects of early life stress as well as parents’ stress have been related to changes in DNA methylation, we will study methylation patterns on a candidate gene basis.

Principal Investigators: Michael Deuschle, Hans-Peter Hammes, Stephanie Witt

MD Student: Bernhard Maier

Inflammatory Bowel Deseases (C3)

ACE and Biological and Psychobiological Markers of Inflammatory Bowel Diseases

ACE take place during a critical phase for the immune system and the intestinal microbiota and may therefore contribute to the development of inflammatory bowel diseases (IBD) later on in life. Altered cognitive processing such as stronger emotional responding as well as the formation of a dysfunctional illness-identity have been discussed but hardly examined in relation to ACE and IBD. To do so, the planned doctoral projects will examine alterations in disease-relevant biological systems (mucosal immune system, intestinal microbiota) and psychobiological processes in the context of ACE and evaluate the differential effects of psychosocial interventions on objective and subjective markers of IBD.

Principal Investigators: S. Lis, W. Reindl

PhD Student: Konstantina Atanasova

Back Pain (C4)

The Impact of Early Social Adversity on the Development of Myofascial Low Back Pain – an Animal Experimental Study

Stress is known to induce or enhance chronic low-back pain. Recent animal experiments indicate that stress itself is able to sensitize nociceptive neurons in the spinal cord. The planned doctoral projects will investigate and compare the impact of ESA and stress on the sensitization process of these neurons in an animal model of myofascial low back pain. Furthermore, experimental interventions will be performed to neutralise or reduce the impact of ESA and stress on the sensitization process of spinal cord dorsal horn neurons.

Principal Investigators: R.-D. Treede, R. Spanagel

PhD Student: Sathish Kumar Singaravelu

Childbirth & Labor Pain (C5)

The Role of ACE for Prenatal Distress, Childbirth Experience and Labor Pain

ACE have been postulated to be associated with alterations in reproductive traits, prenatal maternal distress, childbirth experience, and labor pain as well as pregnancy outcome. However, the evidence is weak, since the number of published studies is limited and study collectives are small, and the influence of type and timing of ACE has hardly been considered. Psychosocial factors may modulate the impact of ACE and should be studied in more detail to develop powerful interventions. The planned doctoral projects will address the influence of type and timing of ACE on the outcomes mentioned above and their modulation by psychosocial factors. Finally, they will search for interventions to minimise adverse effects of ACE on birth experience and discomforts of labor.

Principal Investigators: M. Sütterlin, R.-D. Treede

PhD Student: Wenke Müller