Publications by authors named "Sabine C Herpertz"

169 Publications

A Walk-In Clinic for Newly Arrived Mentally Burdened Refugees: The Patient Perspective.

Int J Environ Res Public Health 2021 Feb 25;18(5). Epub 2021 Feb 25.

Center for Psychosocial Medicine, Department for General Internal Medicine and Psychosomatics, Heidelberg University Hospital, 69115 Heidelberg, Germany.

Providing refugees with psychosocial support is particularly important considering the high level of mental health problems prevalent in this population. A psychosocial walk-in clinic operating within a state reception and registration center in Germany has been supporting mentally burdened refugees since 2016. This study focused on patients' perspectives on their mental health burden, the psychosocial walk-in clinic, and future help seeking. We conducted interviews with = 22 refugees attending the walk-in clinic from March to May 2019. Qualitative analysis focused on the following four topics: (1) mental burden from the patients' perspective, (2) access to the psychosocial walk-in clinic, (3) perception of counseling sessions, and (4) perception of follow-up treatment. The results show that the majority of interviewees were burdened by psychological and somatic complaints, mostly attributed to past experiences and post-migratory stress. Therapeutic counseling and psychiatric medication were found to be particularly helpful. Most of the participants felt motivated to seek further psychosocial support. Key barriers to seeking psychosocial help included shame, fear of stigma, and lack of information. Overall, the psychosocial walk-in clinic is a highly valued support service for newly arrived refugees with mental health issues.
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http://dx.doi.org/10.3390/ijerph18052275DOI Listing
February 2021

A Prospective Study of Mental Health During the COVID-19 Pandemic in Childhood Trauma-Exposed Individuals: Social Support Matters.

J Trauma Stress 2021 Feb 11. Epub 2021 Feb 11.

Department of General Psychiatry, Center for Psychosocial Medicine, Medical Faculty, Heidelberg University, Heidelberg, Germany.

The novel coronavirus disease 2019 (COVID-19) pandemic and its unprecedented social restrictions may have serious mental health implications, especially in individuals who have experienced childhood traumatic experiences (CTEs). This prospective study aimed to investigate whether general psychopathology and posttraumatic stress disorder (PTSD) symptom severity increased during the pandemic as compared to prepandemic baseline data collected approximately 1 year earlier. Furthermore, we investigated whether an increase in symptomatology was linked to CTEs and mediated by a lack of perceived social support and fear of COVID-19. An online survey was administered to 85 individuals, including both participants with PTSD, major depression, or somatic symptom disorder (n = 63) and healthy volunteers (n = 22), during a period of the most severe social restrictions in Germany. The survey included the Childhood Trauma Questionnaire, Brief Symptom Inventory, PTSD Checklist for DSM-5, ENRICHD Social Support Inventory, and Fear of COVID-19 Scale. In the whole sample, we found significant increases in general psychopathology and PTSD symptom severity, ω = .07-.08, during as compared to before the COVID-19 pandemic, with CTEs predicting increased PTSD symptom severity, β = .245, p = .042. This effect was mediated by a lack of perceived social support, indirect effect = .101, 95% CI [.013, .209], but not fear of COVID-19, indirect effect = .060, 95% CI [-.035, .167]. These findings emphasize the importance of interventions that promote social inclusion to mitigate the potentially detrimental effects of public health actions implemented against the COVID-19 pandemic in individuals with CTEs.
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http://dx.doi.org/10.1002/jts.22660DOI Listing
February 2021

An eye-tracking study of interpersonal threat sensitivity and adverse childhood experiences in borderline personality disorder.

Borderline Personal Disord Emot Dysregul 2021 Jan 4;8(1). Epub 2021 Jan 4.

Department of General Psychiatry, Center for Psychosocial Medicine, Medical Faculty, Heidelberg University, Heidelberg, Germany.

Background: Previous eye-tracking studies provide preliminary evidence for a hypersensitivity to negative, potentially threatening interpersonal cues in borderline personality disorder (BPD). From an etiological point of view, such interpersonal threat hypersensitivity might be explained by a biological vulnerability along with a history of early life adversities. The objective of the current study was to investigate interpersonal threat hypersensitivity and its association with adverse childhood experiences (ACE) in patients with BPD employing eye-tracking technology.

Methods: We examined a sample of 46 unmedicated, adult female patients with BPD and 25 healthy female volunteers, matched on age and intelligence, with a well-established emotion classification paradigm with angry, fearful, happy, and neutral facial expressions. ACE were assessed retrospectively with the Childhood Trauma Questionnaire.

Results: Patients as compared to healthy volunteers reflexively directed their gaze more quickly towards the eyes of emotional and neutral faces and did not adapt their fixation patterns according to the facial expression presented. Misclassifying emotional and neutral faces as angry correlated positively with the patients' self-reported ACE.

Conclusions: Building on and extending earlier findings, our results are likely to suggest a visual hypervigilance towards the eyes of emotional and neutral facial expressions and a childhood trauma-related anger bias in patients with BPD. Given the lack of a clinical control group, the question whether these findings are specific for BPD has to remain open. Thus, further research is needed to elucidate the specificity of altered visual attention allocation and the role of ACE in anger recognition in patients with BPD.
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http://dx.doi.org/10.1186/s40479-020-00141-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784013PMC
January 2021

Understanding Brain Mechanisms of Reactive Aggression.

Curr Psychiatry Rep 2020 Nov 12;22(12):81. Epub 2020 Nov 12.

Department of General Psychiatry, Center for Psychosocial Medicine, Medical Faculty, Heidelberg University, Heidelberg, Germany.

Purpose Of Review: To review the current literature on biobehavioral mechanisms involved in reactive aggression in a transdiagnostic approach.

Recent Findings: Aggressive reactions are closely related to activations in the brain's threat circuitry. They occur in response to social threat that is experienced as inescapable, which, in turn, facilitates angry approach rather than fearful avoidance. Provocation-induced aggression is strongly associated with anger and deficits in cognitive control including emotion regulation and inhibitory control. Furthermore, the brain's reward system plays a particular role in anger-related, tit-for-tat-like retaliatory aggression in response to frustration. More research is needed to further disentangle specific brain responses to social threat, provocation, and frustration. A better understanding of the psychological and neurobiological mechanisms involved in reactive aggression may pave the way for specific mechanism-based treatments, involving biological or psychotherapeutic approaches or a combination of the two.
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http://dx.doi.org/10.1007/s11920-020-01208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661405PMC
November 2020

Cognitive and Affective Theory of Mind in Female Patients With Borderline Personality Disorder.

J Pers Disord 2020 Oct 27:1-19. Epub 2020 Oct 27.

Department of General Psychiatry, Heidelberg University, Germany.

Empirical studies have identified deficits in cognitive and affective theory of mind (ToM) in patients with borderline personality disorder (BPD), but results remain heterogeneous and not much is known about the role of childhood trauma. The current study assessed cognitive and affective ToM in 80 patients with BPD and 41 healthy controls in a false-belief cartoon task. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ). Patients with BPD responded slower in all experimental conditions in false-belief situations, but not when false beliefs were resolved; made more errors in the cognitive ToM condition; and reported worse affective states more often in and after false-belief situations. No significant correlations between ToM and childhood trauma could be found. The current study revealed deficits in cognitive and affective ToM in patients with BPD that may be related to a more negative affective state raised by the false-belief stories.
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http://dx.doi.org/10.1521/pedi_2020_34_490DOI Listing
October 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

The Cycle of Abuse: Emotional Availability in Resilient and Non-Resilient Mothers with Early Life Maltreatment.

Psychopathology 2020 16;53(5-6):298-305. Epub 2020 Sep 16.

Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Background: Early life maltreatment (ELM) has a high risk of transmission across generations, known as "the cycle of abuse." ELM is also an important risk factor for developing mental disorders, and having a mental disorder increases the risk of child abuse. Both the abuse potential in mothers with ELM and in mothers with a history of mental disorders might be associated with a disturbed mother-child interaction.

Objective: The current study examined differences in emotional availability between mothers with a history of ELM and previous or current mental disorders (non-resilient), mothers with ELM without mental disorders (resilient), and control mothers without ELM and without mental disorders.

Methods: Thirty-three non-resilient mothers, 18 resilient mothers, and 37 control mothers and their 5- to 12-year-old children participated in a standardized mother-child interaction task. Videotaped interactions were rated by three independent, trained raters based on the Emotional Availability Scales (EA Scales) and compared between the groups.

Results: The non-resilient mothers and their children showed reduced maternal sensitivity, structuring, non-intrusiveness, non-hostility, responsiveness, and involvement compared to the resilient mothers and their children and the control mothers and their children (p = 0.006, ηp2 = 0.12). No differences on any of the EA Scales were found between resilient mothers and control mothers.

Conclusions: These deficits in mother-child interaction in non-resilient mothers might contribute to mechanisms that could explain the cycle of abuse. Interestingly, resilient mothers, who did not develop a mental disorder despite having experienced ELM, did not show these deficits. Thus, prevention programs promoting resilience might be a key to break the cycle of abuse.
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http://dx.doi.org/10.1159/000509904DOI Listing
January 2021

Hair cortisol moderates the association between obstetric complications and child wellbeing.

Psychoneuroendocrinology 2020 11 18;121:104845. Epub 2020 Aug 18.

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Campus Virchow-Klinikum, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Berlin, Germany.

Obstetric complications (OC) may have implications for later health outcomes. However, there is a lack of research examining the association between OC and behavior problems or quality of life (HRQoL). We aimed to close this gap and further investigate functioning of the hypothalamus-pituitary-adrenal (HPA)-axis as a potential physiological vulnerability moderating the association between OC and behavior problems and HRQoL. We investigated 232 mothers and their five to 12-year-old children. Presence of OC during the pre-, peri-, and postnatal phases was determined by interviewing mothers. Children's behavior problems (CBCL, TRF) and HRQoL (Kidscreen rated by mothers and children) were assessed. Children gave 3 cm strands of hair for analysis of hair cortisol (HC). Structural equation modeling analyses with a latent variable of child outcome ("distress"), OC as predictor and HC as a potential moderator were conducted. OC significantly predicted distress (β = .33, p < .01). The model showed a good fit to the data: χ2(14)=15.66, p < .33, CFI=.99, TLI=.99, RMSEA=.02, 90 %CI [.00, .06], SRMR=.04. In addition, HC moderated the association between OC and distress (β=-.32, p < .01). The moderation model also showed a good fit: χ2(14) =7.13, p = .93, CFI=1.00, TLI=1.06, RMSEA=.00, 90 %CI [.00, .02], SRMR=.03. Results indicated that the association between OC and distress was significant only when children had low HC-levels. This was also the case for both externalizing and internalizing behavior problems. Our results underline the notion of OC as a risk factor for child behavior problems and wellbeing and point to an important role of the children's physiological set-up such as HPA-functioning.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104845DOI Listing
November 2020

Early life maltreatment and depression: Mediating effect of maternal hair cortisol concentration on child abuse potential.

Psychoneuroendocrinology 2020 10 6;120:104791. Epub 2020 Jul 6.

Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.

Introduction: Maternal early life maltreatment (ELM) and history of depression can bear a risk for adverse development in the child. One neurobiological pathway for the transmission of both maternal ELM and remitted depression (MDD) might be altered maternal cortisol levels. In the present study, we examine (1) main and interacting effects of maternal ELM and remitted MDD on hair cortisol concentration (HCC) in mothers, whether (2) maternal HCC explains the association between maternal ELM or remitted MDD and maternal child abuse potential, and (3) whether maternal child abuse potential as well as maternal HCC are associated with maternal report of child well-being.

Methods: The current study involved 127 mother-child dyads. Maternal history of ELM and psychopathology were assessed via the Mini International Neuropsychiatric Interview (M.I.N.I.) and Childhood Experience and Care (CECA) interview. The Child Abuse Potential Inventory (CAPI) was used to assess maternal child abuse and neglect potential. We applied the Kidscreen-27 parent report to study child well-being. To assess HCC, hair strands were taken from the mothers. To test the research questions, a two-factorial analysis of covariance, mediation analysis using ordinary least squares regressions with bootstrapping, and Pearson correlations were calculated.

Results: Mothers with ELM had significantly increased HCC. There was no effect of remitted MDD on HCC, nor an interaction effect of both factors. HCC was a significant mediator of the association between maternal ELM and maternal child abuse potential. Maternal child abuse potential as well as HCC were significantly associated with reduced child well-being.

Discussion: Our data suggest that adverse experiences in childhood are associated with altered HPA-axis functioning reflected in increased levels of HCC. HPA-axis activity is not altered in mothers with remitted MDD. From a clinical point of view, one might speculate that the partially mediating effect of maternal HCC could indicate a starting point in the prevention of the intergenerational cycle of abuse.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104791DOI Listing
October 2020

[New insights into diagnostics and therapy of personality disorders-Changes in ICD-11].

Nervenarzt 2020 Sep;91(9):863-871

Klinik für Allgemeine Psychiatrie, Universitätsklinikum Heidelberg, Voßstr. 2, 69115, Heidelberg, Deutschland.

Personality disorders (PD) occur frequently and show high remission rates in the long term, while psychosocial recovery remains unsuccessful in a substantial proportion of cases. In ICD-11 the traditional view that PDs have a high stability is abandoned. Instead, the minimum duration is 2 years. The diagnostic process differentiates between three degrees of severity (mild, moderate, severe) and five prominent personality trait domains. Optionally, a borderline qualifying factor can be additionally codified. There is sufficient empirical evidence only for the treatment of borderline PD (BPD). Disorder-specific psychotherapy, in particular dialectic behavioral therapy (DBT) and mentalization-based therapy (MBT) have proven to be effective. Therapy modules targeting functional impairments and prominent personality trait domains could close the existing gaps in the disorder-specific treatment of PD.
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http://dx.doi.org/10.1007/s00115-020-00936-7DOI Listing
September 2020

Intact Classical Fear Conditioning to Interpersonally Threatening Stimuli in Borderline Personality Disorder.

Psychopathology 2020 12;53(2):84-94. Epub 2020 Jun 12.

Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Threat hypersensitivity is regarded as a central mechanism of deficient emotion regulation, a core feature of patients with borderline personality disorder (BPD). Here, we employed a classical fear-conditioning protocol in which interpersonally threatening, interpersonally non-threatening, and non-social (neutral) visual stimuli were predictive of an aversive auditory stimulus in a sample of 23 medication-free adult female patients with BPD and 21 age- and IQ-matched healthy women. The results did not confirm the hypothesized enhanced and prolonged conditioned skin conductance responses (SCR) and subjective stress and expectancy ratings to interpersonally threatening stimuli in patients with BPD compared to healthy women. Patients with BPD generally expected the aversive stimulus more often irrespective of stimulus category and conditioning. Furthermore, patients with BPD showed larger conditioned SCR to interpersonally non-threatening and neutral than interpersonally threatening stimuli, while interpersonally threatening stimuli elicited higher SCR compared to non-threatening or neutral stimuli in healthy controls. Together with previous studies, the results suggest no alterations in fear conditioning to generally aversive stimuli in BPD. Further studies using stimuli with BPD-specific topics, such as abandonment or rejection, and/or to investigate more interpersonal forms of learning, such as observational or instructed conditioning, are urgently needed to further elucidate the mechanisms involved in the etiology and maintenance of threat hypersensitivity in BPD.
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http://dx.doi.org/10.1159/000507794DOI Listing
September 2020

Maternal early life maltreatment and psychopathology affect the next generation: Alterations in post-awakening cortisol levels of primary school-aged children.

Dev Psychobiol 2021 Jan 4;63(1):98-107. Epub 2020 Jun 4.

Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.

Early life maltreatment (ELM) has severe and lasting effects on the individual, which might also impact the next generation. On an endocrine level, the hypothalamus-pituitary-adrenal axis has been suggested to play an important role in the interplay between ELM and the development of mental disorders. Several studies have revealed that maternal post-awakening cortisol concentration, maternal sensitivity, maternal ELM and psychopathology are associated with children's cortisol levels. We investigated the post-awakening cortisol concentrations in 6- to 11-year-old children (N = 53) whose mothers either had experienced ELM and had developed a lifetime mental disorder (N = 15 ELM and disorder group), had experienced ELM without developing a mental disorder (N = 12 ELM-only group), or had neither experienced ELM nor developed a mental disorder (N = 26 HC-group). Furthermore, we assessed maternal post-awakening cortisol concentrations, maternal psychopathology, and sensitivity. Multilevel analysis revealed higher cortisol at awakening (S1) levels in children of mothers with ELM and disorder. Maternal cortisol at awakening (S1) also predicted the child's cortisol at awakening (S1), and no effect of maternal sensitivity could be found. The current results replicate an attunement of cortisol levels (S1) between mothers and children and suggest an association between the children's endocrine stress system and maternal factors such as ELM and psychopathology.
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http://dx.doi.org/10.1002/dev.21996DOI Listing
January 2021

Pain-modulating effects of oxytocin in patients with chronic low back pain.

Neuropharmacology 2020 07 13;171:108105. Epub 2020 Apr 13.

Department of General Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Germany. Electronic address:

The neuropeptide oxytocin (OT) has been shown to play a modulatory role in nociception. However, analgesic effects of OT in chronic pain conditions remain elusive and the neural underpinnings have not yet been investigated in humans. Here, we conducted an exploratory, randomized, placebo-controlled, cross-over study to examine effects of intranasal OT in male patients suffering from chronic low back pain (CBP) versus healthy controls (HC). N = 22 participants with CBP and 22 HCs were scanned using functional magnetic resonance imaging (fMRI) while they continuously rated either spontaneously occurring back pain or acute thermal pain stimuli applied to the lower back. During heat pain processing we found that OT versus PL attenuated pain intensity ratings and increased BOLD responses in the caudate nucleus of the striatum in CBP versus HCs. Spontaneously experienced pain in contrast to heat pain was associated with activation changes in the medial frontal cortex (MFC) and the anterior cingulate cortex (ACC) as reported in previous studies. However, we did not observe OT effects on spontaneously experienced pain in CBP patients. Overall, our preliminary data may suggest that the striatum is a key structure underlying the pain-modulating effects of OT in patients with chronic pain and adds to the growing evidence linking the neuropeptide to pain modulation in humans. Further studies on neuronal OT effects in larger samples of chronic back pain patients are needed to understand probable mechanisms of OT effects in chronic pain. This article is part of the special issue on Neuropeptides.
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http://dx.doi.org/10.1016/j.neuropharm.2020.108105DOI Listing
July 2020

Oxytocin Normalizes Approach-Avoidance Behavior in Women With Borderline Personality Disorder.

Front Psychiatry 2020 11;11:120. Epub 2020 Mar 11.

Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Interpersonal deficits are a core symptom of borderline personality disorder (BPD), which could be related to increased social threat sensitivity and a tendency to approach rather than avoid interpersonal threats. The neuropeptide oxytocin has been shown to reduce threat sensitivity in patients with BPD and to modify approach-avoidance behavior in healthy volunteers. In a randomized, double-blind placebo-controlled between-subject design, 53 unmedicated women with BPD and 61 healthy women participated in an approach-avoidance task 75 min after intranasal substance administration (24 IU of oxytocin or placebo). The task assesses automatic approach-avoidance tendencies in reaction to facial expressions of happiness and anger. While healthy participants responded faster to happy than angry faces, the opposite response pattern, that is, faster reactions to angry than happy faces, was found in patients with BPD. In the oxytocin condition, the "congruency effect" (i.e., faster avoidance of facial anger and approach of facial happiness vice versa) was increased in both groups. Notably, patients with BPD exhibited a congruency effect toward angry faces in the oxytocin but not in the placebo condition. This is the second report of deficient fast, automatic avoidance responses in terms of approach behavior toward interpersonal threat cues in patients with BPD. Intranasally administered oxytocin was found to strengthen avoidance behavior to social threat cues and, thus, to normalize fast action tendencies in BPD. Together with the previously reported oxytocinergic reduction of social threat hypersensitivity, these results suggest beneficial effects of oxytocin on interpersonal dysfunctioning in BPD.
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http://dx.doi.org/10.3389/fpsyt.2020.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078372PMC
March 2020

Oxytocin Normalizes Approach-Avoidance Behavior in Women With Borderline Personality Disorder.

Front Psychiatry 2020 11;11:120. Epub 2020 Mar 11.

Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Interpersonal deficits are a core symptom of borderline personality disorder (BPD), which could be related to increased social threat sensitivity and a tendency to approach rather than avoid interpersonal threats. The neuropeptide oxytocin has been shown to reduce threat sensitivity in patients with BPD and to modify approach-avoidance behavior in healthy volunteers. In a randomized, double-blind placebo-controlled between-subject design, 53 unmedicated women with BPD and 61 healthy women participated in an approach-avoidance task 75 min after intranasal substance administration (24 IU of oxytocin or placebo). The task assesses automatic approach-avoidance tendencies in reaction to facial expressions of happiness and anger. While healthy participants responded faster to happy than angry faces, the opposite response pattern, that is, faster reactions to angry than happy faces, was found in patients with BPD. In the oxytocin condition, the "congruency effect" (i.e., faster avoidance of facial anger and approach of facial happiness vice versa) was increased in both groups. Notably, patients with BPD exhibited a congruency effect toward angry faces in the oxytocin but not in the placebo condition. This is the second report of deficient fast, automatic avoidance responses in terms of approach behavior toward interpersonal threat cues in patients with BPD. Intranasally administered oxytocin was found to strengthen avoidance behavior to social threat cues and, thus, to normalize fast action tendencies in BPD. Together with the previously reported oxytocinergic reduction of social threat hypersensitivity, these results suggest beneficial effects of oxytocin on interpersonal dysfunctioning in BPD.
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http://dx.doi.org/10.3389/fpsyt.2020.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078372PMC
March 2020

Oxytocin modulates intrinsic neural activity in patients with chronic low back pain.

Eur J Pain 2020 05 9;24(5):945-955. Epub 2020 Mar 9.

Department of General Psychiatry, Center of Psychosocial Medicine, Heidelberg University, Heidelberg, Germany.

Background: Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP).

Methods: Twenty-four male patients with cLBP and 23 healthy males were examined using resting-state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 min before scanning. The fractional amplitude of low-frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT-effects on functional network strength.

Results: Differential effects of OXT were observed in cLBP and healthy controls. FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group-specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus and right amygdala with pain-specific psychometric scores in cLBP.

Conclusions: These data suggest OXT-related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT.

Significance: Our data suggest significant oxytocin-related modulation of intrinsic regional activity and neural network strength in patients with chronic low back pain and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by oxytocin. Therapeutic effects of oxytocin for improved pain treatment need to be further investigated.
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http://dx.doi.org/10.1002/ejp.1543DOI Listing
May 2020

Heart and brain: Cortical representation of cardiac signals is disturbed in borderline personality disorder, but unaffected by oxytocin administration.

J Affect Disord 2020 03 30;264:24-28. Epub 2019 Nov 30.

Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany; Department of Psychology, LMU Munich, Munich, Germany. Electronic address:

Background: Emotional dysregulation, a core feature of borderline personality disorder (BPD) has recently been linked to deficits in the cortical representation of bodily signals. Oxytocin modulates the salience of external social cues. However, its role in interoception is still not fully understood. The aim of the current study was to replicate reduced heartbeat-evoked potentials (HEPs) as a marker for the cortical representation of cardiac signals in BPD and to explore potential effects of oxytocin on HEP amplitude.

Methods: Fifty-three medication-free women with a DSM-IV diagnosis of BPD and sixty healthy female controls (HCs) participated in the study. In a randomized, double-blind placebo-controlled trial, participants self-administered either 24 I.U. of oxytocin or placebo and took part in a 5-minute resting-state electrocardiogram (ECG) with parallel electroencephalogram (EEG) measurement. In addition, emotional dysregulation and BPD symptomatology were assessed with self-report questionnaires.

Results: Patients with BPD had significantly lower mean HEP amplitudes than HCs. Furthermore, HEP amplitudes were negatively correlated with emotional dysregulation in the whole sample. However, oxytocin had no significant effect on HEP amplitude.

Limitations: Only female participants were investigated and no clinicial controls were included.

Conclusions: This is the first replication from an independent sample showing a reduced cortical representation of cardiac signals in BPD patients. This, together with other body-related symptoms, suggests deficits in the processing of bodily signals, which seem to be associated with emotional dysregulation. Whether oxytocin influences HEP during emotion regulation tasks needs to be investigated in future studies.
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http://dx.doi.org/10.1016/j.jad.2019.11.139DOI Listing
March 2020

[Borderline Personality Disorders].

Z Kinder Jugendpsychiatr Psychother 2020 Nov 22;48(6):1-5. Epub 2019 Nov 22.

Klinik für Psychosomatik, Zentralinstitut für Seelische Gesundheit, Mannheim, Deutschland.

Borderline Personality Disorders Within the framework of the German task force "Transitional Psychiatry" (DGKJP and DGPPN), a group of experts discussed the significance of adolescence for the mental healthcare of Borderline Personality Disorder (BPD) in Germany. They identified particular gaps and problems within the following areas: early detection, access to specific outpatient psychotherapy, prolonged inpatient treatment, and polypharmacy. The authors then describe various recommendations and demands regarding the generation and dissemination of knowledge about BPD as well as potential adaptations within the German healthcare system.
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http://dx.doi.org/10.1024/1422-4917/a000700DOI Listing
November 2020

The Sound and Face of Others: Vocal Priming Effects on Facial Emotion Processing in Posttraumatic Stress Disorder.

Psychopathology 2019 30;52(5):283-293. Epub 2019 Oct 30.

Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Introduction: Facial expressions and vocal intonation are key signals in the communication of emotions. Individuals with posttraumatic stress disorder (PTSD) are known to show an impaired perception of facial emotions. So far, research on multimodal emotional stimuli or the priming effects on emotion processing has been absent in PTSD. Therefore, we conducted a study to investigate the influence of vocal priming on facial emotion processing and classification in PTSD using electroencephalography.

Methods: Twenty-one women with PTSD compared to 28 healthy women were asked to classify emotion-morphed faces with predominantly angry, ambiguous, or predominantly happy expressions primed by either an angry or a happy voice. Responses and reaction times as well as the N170, a component reflecting configural face processing, were analyzed.

Results: Patients with PTSD were slower in classifying emotional faces that were primed by either an angry or happy voice compared to the healthy controls (HCs; η2 = 0.14). Additionally, patients with PTSD were faster in classifying facial expressions after angry compared to happy vocal primes (η2 = 0.14). HCs did not show this effect. Correlation analyses revealed positive associations between emotion (dys-)regulation and reaction times in patients with PTSD but not in HCs (r = 0.64-0.76). Furthermore, patients with PTSD showed greater N170 amplitudes for predominantly angry and ambiguous faces than HCs (η2 = 0.07).

Conclusion: Data suggest that patients with PTSD experience more difficulties when processing complex social stimuli than HCs. The altered processing of complex social-emotional signals could amplify PTSD symptoms, thus qualifying as an explicit therapy target.
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http://dx.doi.org/10.1159/000503584DOI Listing
March 2020

Mentalization and criterion a of the alternative model for personality disorders: Results from a clinical and nonclinical sample.

Personal Disord 2020 05 2;11(3):191-201. Epub 2019 Sep 2.

Department for Psychosocial Prevention.

Criterion A of the alternative model for the classification of personality disorders in the ), introduced the Level of Personality Functioning Scale (LPFS), a dimensional model for the assessment of impairments in self and interpersonal functioning. The LPFS was developed based on a review of different measures of personality functioning, such as the Reflective Functioning Scale, a measure of mentalizing. This study investigated the empirical overlap between the LPFS and mentalization. The study sample included adult inpatients ( = 55) with a mental disorder and a healthy adult control group ( = 55). All participants were examined regarding the LPFS using the Semistructured Interview for Personality Functioning ; mentalizing was assessed with the Brief Reflective Functioning Interview and coded with the Reflective Functioning Scale. We used structural equation modeling to investigate the relationship between LPFS domains and mentalization. Correlation analysis was used to examine the agreement between interview-rated LPFS and self-report measures of personality dysfunction. All domains of the LPFS were significantly related to mentalizing. Interview-rated LPFS was significantly associated with self-reported personality dysfunction. The findings support the notion that the LPFS and mentalization share a strong conceptual and operational overlap by demonstrating that both constructs are empirically interrelated. The results yield further support for the validity of the LPFS as a dimensional model for the assessment of personality disorder severity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/per0000356DOI Listing
May 2020

Individualized treatment response prediction of dialectical behavior therapy for borderline personality disorder using multimodal magnetic resonance imaging.

Brain Behav 2019 09 14;9(9):e01384. Epub 2019 Aug 14.

Department of General Psychiatry, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

Introduction: Individualized treatment prediction is crucial for the development and selection of personalized psychiatric interventions. Here, we use random forest classification via pretreatment clinical and demographical (CD), functional, and structural magnetic resonance imaging (MRI) data from patients with borderline personality disorder (BPD) to predict individual treatment response.

Methods: Before dialectical behavior therapy (DBT), 31 female patients underwent functional (three different emotion regulation tasks) and structural MRI. DBT response was predicted using CD and MRI data in previously identified anatomical regions, which have been reported to be multimodally affected in BPD.

Results: Amygdala and parahippocampus activation during a cognitive reappraisal task (in contrasts displaying neural activation for emotional challenge and for regulation), along with severity measures of BPD psychopathology and gray matter volume of the amygdala, provided best predictive power with neuronal hyperractivities in nonresponders. All models, except one model using CD data solely, achieved significantly better accuracy (>70.25%) than a simple all-respond model, with sensitivity and specificity of >0.7 and >0.7, as well as positive and negative likelihood ratios of >2.74 and <0.36 each. Surprisingly, a model combining all data modalities only reached rank five of seven. Among the functional tasks, only the activation elicited by a cognitive reappraisal paradigm yielded sufficient predictive power to enter the final models.

Conclusion: This proof of principle study shows that it is possible to achieve good predictions of psychotherapy outcome to find the most valid predictors among numerous variables via using a random forest classification approach.
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http://dx.doi.org/10.1002/brb3.1384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749487PMC
September 2019

Individualized treatment response prediction of dialectical behavior therapy for borderline personality disorder using multimodal magnetic resonance imaging.

Brain Behav 2019 09 14;9(9):e01384. Epub 2019 Aug 14.

Department of General Psychiatry, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

Introduction: Individualized treatment prediction is crucial for the development and selection of personalized psychiatric interventions. Here, we use random forest classification via pretreatment clinical and demographical (CD), functional, and structural magnetic resonance imaging (MRI) data from patients with borderline personality disorder (BPD) to predict individual treatment response.

Methods: Before dialectical behavior therapy (DBT), 31 female patients underwent functional (three different emotion regulation tasks) and structural MRI. DBT response was predicted using CD and MRI data in previously identified anatomical regions, which have been reported to be multimodally affected in BPD.

Results: Amygdala and parahippocampus activation during a cognitive reappraisal task (in contrasts displaying neural activation for emotional challenge and for regulation), along with severity measures of BPD psychopathology and gray matter volume of the amygdala, provided best predictive power with neuronal hyperractivities in nonresponders. All models, except one model using CD data solely, achieved significantly better accuracy (>70.25%) than a simple all-respond model, with sensitivity and specificity of >0.7 and >0.7, as well as positive and negative likelihood ratios of >2.74 and <0.36 each. Surprisingly, a model combining all data modalities only reached rank five of seven. Among the functional tasks, only the activation elicited by a cognitive reappraisal paradigm yielded sufficient predictive power to enter the final models.

Conclusion: This proof of principle study shows that it is possible to achieve good predictions of psychotherapy outcome to find the most valid predictors among numerous variables via using a random forest classification approach.
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http://dx.doi.org/10.1002/brb3.1384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749487PMC
September 2019

Stabilizing Techniques and Guided Imagery for Traumatized Male Refugees in a German State Registration and Reception Center: A Qualitative Study on a Psychotherapeutic Group Intervention.

J Clin Med 2019 Jun 22;8(6). Epub 2019 Jun 22.

Center for Psychosocial Medicine, Department for General Internal Medicine and Psychosomatics, University Hospital of Heidelberg, 69115 Heidelberg, Germany.

Refugees have an increased risk of developing mental health problems. Due to the unstable setting in refugee state registration and reception centers, recommended trauma-focused treatment approaches are often not applicable. For this purpose, we devised a suitable therapeutic approach to treat traumatized refugees in a German state registration and reception center: Group therapy, focusing on stabilizing techniques and guided imagery according to Reddemann (2017). From May 2017 to April 2018, we conducted semi-structured interviews with = 30 traumatized refugees to assess their experiences with the stabilizing techniques and guided imagery in group sessions and self-practice. Participants mainly reported that they had more pleasant feelings, felt increasingly relaxed, and could better handle recurrent thoughts. Additionally, the participants noticed that their psychosocial functioning had improved. The main difficulties that participants encountered were feeling stressed, having difficulties staying focused, or concentrating on the techniques. During self-practice, the participants found it most challenging that they did not have any verbal guidance, were often distracted by the surroundings in the accommodation, and had recurrent thoughts about post-migratory stressors, such as insecurity concerning the future or the application for asylum. Our results show that stabilizing techniques and guided imagery according to Reddemann (2017) are a suitable approach to treat traumatized refugees living in volatile conditions.
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http://dx.doi.org/10.3390/jcm8060894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617260PMC
June 2019

Alterations of empathy in mothers with a history of early life maltreatment, depression, and borderline personality disorder and their effects on child psychopathology.

Psychol Med 2020 05 22;50(7):1182-1190. Epub 2019 May 22.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Campus Virchow-Klinikum, Berlin, Germany.

Background: Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology.

Methods: We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5-12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology.

Results: Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress.

Conclusion: The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.
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http://dx.doi.org/10.1017/S0033291719001107DOI Listing
May 2020

A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System.

Neuron 2019 07 16;103(1):133-146.e8. Epub 2019 May 16.

Schaller Research Group on Neuropeptides, German Cancer Research Center, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany; Department of Neuropeptide Research for Psychiatry, Central Institute of Mental Health, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address:

Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram.
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http://dx.doi.org/10.1016/j.neuron.2019.04.029DOI Listing
July 2019

Childhood adversity and parenting behavior: the role of oxytocin receptor gene polymorphisms.

J Neural Transm (Vienna) 2019 06 16;126(6):777-787. Epub 2019 May 16.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg, Regensburg, Germany.

Previous research revealed experiences of childhood adversity (CA) to be related to less favorable parenting behavior. It can further be expected that maternal oxytocin receptor (OXTR) genes may influence parenting behavior and moderate relationships between CA and parenting behavior. Moreover, associations between the OXTR gene and plasma oxytocin (OT) have been discussed. The present study investigated main effects of the OXTR gene on parenting behavior and plasma OT of mothers, and moderating effects of the OXTR gene on the relationship between mothers' experiences of CA and parenting behavior. We relied on a sample of 193 mothers and their on average 8-year-old children. Maternal experiences of CA were assessed using a standardized interview. A questionnaire for the assessment of child abuse potential and observations of mother-child interaction were used as indicators of parenting behavior. For mothers, we analyzed three polymorphisms (rs53576, rs1042778, rs2254298) of the OXTR gene and plasma OT. Only the rs53576 was associated with mothers' parenting behavior, specifically with maternal sensitivity. The rs2254298 significantly moderated relations between mothers' experiences of CA and parenting behavior. Significant relations could be found only for mothers who were homozygous for the G allele. The G allele of the rs2254298 was further related to increased plasma OT levels. Our findings underline the importance of considering genetic variation when investigating consequences of CA and developing intervention programs that are adapted to an individual's needs.
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http://dx.doi.org/10.1007/s00702-019-02009-9DOI Listing
June 2019

[Erratum to: Oxytocin and maltreatment potential : Influence of maternal depression, borderline personality disorder and experience of early childhood maltreatment].

Nervenarzt 2019 Jul;90(7):732

Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Psychiatrische Universitätsklinik der Charité im St. Hedwig-Krankenhaus, Große Hamburger Straße 5-11, 10115, Berlin, Deutschland.

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http://dx.doi.org/10.1007/s00115-019-0729-zDOI Listing
July 2019

Oxytocin Effects on Pain Perception and Pain Anticipation.

J Pain 2019 10 19;20(10):1187-1198. Epub 2019 Apr 19.

Department of General Psychiatry, University Hospital of Heidelberg, Heidelberg, Germany.

There is an ongoing debate whether the neuropeptide oxytocin (OT) modulates pain processing in humans. This study differentiates behavioral and neuronal OT effects on pain perception and pain anticipation by using a Pavlovian conditioning paradigm. Forty-six males received intranasally administered OT in a randomized, double-blind, placebo-controlled group design. Although OT exerted no direct effect on perceived pain, OT was found to modulate the blood oxygen level-dependent response in the ventral striatum for painful versus warm unconditioned stimuli and to decrease activity in the anterior insula (IS) with repeated thermal pain stimuli. Regarding pain anticipation, OT increased responses to CS versus CS in the nucleus accumbens. Furthermore, in the OT condition increased correct expectations, particularly for the most certain conditioned stimuli (CS)-unconditioned stimuli associations (CS and CS) were found, as well as greatest deactivations in the right posterior IS in response to the least certain condition (CS) with posterior IS activity and correct expectancies being positively correlated. In conclusion, OT seems to have both a direct effect on pain processing via the ventral striatum and by inducing habituation in the anterior IS as well as on pain anticipation by boostering associative learning in general and the neuronal conditioned fear of pain response in particular. PERSPECTIVE: The neuropeptide OT has recently raised the hope to offer a novel avenue for modulating pain experience. This study found OT to modulate pain processing and to facilitate the anticipation of pain, inspiring further research on OT effects on the affective dimension of the pain experience.
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http://dx.doi.org/10.1016/j.jpain.2019.04.002DOI Listing
October 2019

An experimental study on spontaneous recovery of conditioned reward expectancies and instrumental responding in humans.

Behav Res Ther 2019 07 21;118:54-64. Epub 2019 Mar 21.

Sussex Addiction Research and Intervention Centre, School of Psychology, University of Sussex, Falmer, Brighton, BN1 9QH, UK.

The aim of the present study was to investigate spontaneous recovery of reward-expectancies and a reward-associated response in humans and to assess individual factors affecting spontaneous recovery. We therefore implemented an experimental procedure comprising three separate test-sessions. In the first test-session, participants underwent instrumental discrimination training to acquire a conditioned reward-associated response, in the second test-session, memory of this response was tested followed by extinction training. In the third test-session, extinction memory was assessed. Our results demonstrate spontaneous recovery of extinguished conditioned reward-associated expectancies and indicate that differential expectancies after training and extinction and impulsivity significantly predicted the magnitude of spontaneous recovery. In contrast, limited evidence for spontaneous recovery of instrumental responding was found. Given that reward-expectancies might trigger instrumental responding these findings underline the importance of developing extinction procedures that lead to more complete and less fragile long-term extinction of reward-associated responses.
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http://dx.doi.org/10.1016/j.brat.2019.03.010DOI Listing
July 2019