[New insights into diagnostics and therapy of personality disorders-Changes in ICD-11]. / Neues zur Diagnostik und Therapie von Persönlichkeitsstörungen ­ Änderungen in ICD­11.

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.

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.

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 n = 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.

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

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.

Whole-brain functional connectivity during script-driven aggression in borderline personality disorder.

OBJECTIVE: Intense anger and anger-related aggression are frequently reported by patients with borderline personality disorders (BPD). Recent results suggest that anger-related aggression and its control is associated with a complex interplay of different neural systems in BPD. To further investigate this, we complement standard activation and seed-based connectivity analyses by examining whole-brain changes in functional connectivity during anger and reactive aggression in BPD. METHODS: We reanalyzed functional MRI data from 33 women with BPD, all of them fulfilling BPD criterion 8, "anger proneness", according to DSM-IV, and 30 healthy women. Subjects performed a script-driven imagery task consisting of four phases: baseline, anger-induction by a narrative of interpersonal rejection, a narrative of directing physical aggression towards others, and relaxation. We used a data-driven, spatially constrained spectral clustering approach to parcellate the brain into 200 regions. For each script-phase and subject, we computed the full connectivity matrix using wavelet coefficient correlations in the 0.05-0.10 Hz range. We calculated the individual increase in connectivity from baseline to the anger-induction and physical aggression phases by subtracting the corresponding connectivity matrices per subject, as well as the increase and decrease from the anger-induction to the aggression phase. We then applied permutation-based sampling to determine a combined threshold on the strength of individual connections and the size of the discovered networks for these difference matrices. RESULTS: We discovered a single, large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. This network consisted of regions in the anterior and posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, superior and middle temporal gyrus, hippocampus, insula, ventrolateral and dorsolateral prefrontal cortex, superior parietal lobe, thalamus, precentral and postcentral gyrus, caudate, pallidum, cerebellum, middle occipital lobe, lingual gyrus, calcarine sulcus, and fusiform gyrus. Hub regions with highest node centrality were found in the right caudate and left thalamus. We found no significant differences for the increase of connectivity from baseline to anger-induction, as well as for the increase or decrease from the anger-induction to the aggression phase. CONCLUSIONS: We identified a large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. The regions constituting this network belong to four previously described functional networks: The frontoparietal cognitive control network, the extended default mode network, the visual system, and the motor system. This stronger increase in connectivity between regions of different functional brain systems associated with cognitive control of behavior, socio-affective and self-referential thinking, as well as salience processing and emotion regulation, visual perception, and action is mediated via hubs in the thalamus and caudate, i.e., core components of the thalamocorticostriatal motor loop essential for action selection and initiation. These findings suggest increased interaction of prefrontal cognitive control processes with thalamocorticostriatal action-selection processes in female patients with BPD during the processing of aggressive action impulses, which are facilitated by states of high emotional salience and associated processes of self-referential and social processing, and ineffective emotion regulation.

The maternal brain in women with a history of early-life maltreatment: an imagination-based fMRI study of conflictual versus pleasant interactions with children.

BACKGROUND: Early-life maltreatment has severe consequences for the affected individual, and it has an impact on the next generation. To improve understanding of the intergenerational effects of abuse, we investigated the consequences of early-life maltreatment on maternal sensitivity and associated brain mechanisms during mother-child interactions. METHODS: In total, 47 mothers (22 with a history of physical and/or sexual childhood abuse and 25 without, all without current mental disorders) took part in a standardized real-life interaction with their 7- to 11-year-old child (not abused) and a subsequent functional imaging script-driven imagery task. RESULTS: Mothers with early-life maltreatment were less sensitive in real-life mother-child interactions, but while imagining conflictual interactions with their child, they showed increased activation in regions of the salience and emotion-processing network, such as the amygdala, insula and hippocampus. This activation pattern was in contrast to that of mothers without early-life maltreatment, who showed higher activations in those regions in response to pleasant mother-child interactions. Mothers with early-life maltreatment also showed reduced functional connectivity between regions of the salience and the mentalizing networks. LIMITATIONS: Region-of-interest analyses, which were performed in addition to whole-brain analyses, were exploratory in nature, because they were not further controlled for multiple comparisons. CONCLUSION: Results suggest that for mothers with early-life maltreatment, conflictual interactions with their child may be more salient and behaviourally relevant than pleasant interactions, and that their salience network is poorly modulated by the brain regions involved in mentalizing processes. This activation pattern offers new insights into the mechanisms behind the intergenerational effects of maltreatment and into options for reducing these effects.

Brain Mechanisms Underlying Reactive Aggression in Borderline Personality Disorder-Sex Matters.

BACKGROUND: Aggression in borderline personality disorder (BPD) is thought to be mediated through emotion dysregulation via high trait anger. Until now, data comparing anger and aggression in female and male patients with BPD have been widely missing on the behavioral and particularly the brain levels. METHODS: Thirty-three female and 23 male patients with BPD and 30 healthy women and 26 healthy men participated in this functional magnetic resonance imaging study. We used a script-driven imagery task consisting of narratives of both interpersonal rejection and directing physical aggression toward others. RESULTS: While imagining both interpersonal rejection and acting out aggressively, a sex × group interaction was found in which male BPD patients revealed higher activity in the left amygdala than female patients. In the aggression phase, men with BPD exhibited higher activity in the lateral orbitofrontal and dorsolateral prefrontal cortices compared with healthy men and female patients. Positive connectivity between amygdala and posterior middle cingulate cortex was found in female patients but negative connectivity was found in male patients with BPD. Negative modulatory effects of trait anger on amygdala-dorsolateral prefrontal cortex and amygdala-lateral orbitofrontal cortex coupling were shown in male BPD patients, while in female patients trait anger positively modulated dorsolateral prefrontal cortex-amygdala coupling. Trait aggression was found to positively modulate connectivity of the left amygdala to the posterior thalamus in male but not female patients. CONCLUSIONS: Data suggest poor top-down adjustment of behavior in male patients with BPD despite their efforts at control. Female patients appear to be less aroused through rejection and to successfully dampen aggressive tension during the imagination of aggressive behavior.

Altered serum fatty acid composition in geriatric depression.

Fatty acids (FA), mainly polyunsaturated (PUFA) of n-3 or n-6 types, may influence neuropsychobiological processes. Decreased levels of n-3 PUFA have been shown to be related to major depression and supplementation of n-3 PUFA seems to contribute to improved depression treatment outcome. The profiles of serum FA profiles in patients with geriatric depression have not been thoroughly studied yet. The present study investigated the FA profiles of patients with geriatric depression and of mentally healthy elderly individuals. Serum FA profiles of 36 inpatients with geriatric depression who fulfilled DSM-IV criteria for unipolar major depression were compared with those of 37 control subjects. Patients with geriatric depression, irrespective of gender, exhibited lower total FAs, as well as significantly lower concentrations of total n-3 PUFA and eicosapentaenoic acid, though the groups did not differ with regard to Body Mass Index. The findings of the present study point to an association between lower FA serum levels and geriatric depression. Further investigations with larger samples and dietetic interventions may provide deeper insights into the role of eicosapentaenoic acid and total n-3 PUFA in the development and treatment of geriatric depression.

Morphometric differences in central stress-regulating structures between women with and without borderline personality disorder.

BACKGROUND: Experiences of early life stress, increased psychological arousal and the body's physiologic stress response seem to play an important role in the pathogenesis and maintenance of borderline personality disorder (BPD). In the present study, we investigated alterations in grey matter of central stress-regulating structures in female patients with BPD. METHODS: We examined T1-weighted structural magnetic resonance imaging scans of unmedicated, right-handed female patients with BPD (according to DSM-IV criteria) and healthy controls matched for age, intelligence and education using fully automated DARTEL voxel-based morphometry. Our regions of interest analyses included the hippocampus, amygdala, anterior cingulate cortex (ACC) and hypothalamus. RESULTS: We enrolled 30 patients and 33 controls in our study. The grey matter of patients with BPD was reduced in the hippocampus, but increased in the hypothalamus compared with healthy participants. Hypothalamic volume correlated positively with the history of traumatization in patients with BPD. No significant alterations were found in the amygdala and ACC. LIMITATIONS: This study is limited by the lack of measures of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol levels. Furthermore, moderate sample size and comorbid disorders need to be considered. CONCLUSION: Our findings provide new evidence for grey matter alterations in the hypothalamus and replicate previously reported decrements in hippocampal volume in patients with BPD. Understanding the role of the hypothalamus and other central stress-regulating structures could help us to further understand the neurobiological underpinnings of this complex disorder.

Effects of experimental acute tryptophan depletion on acoustic startle response in females.

Previous studies suggest an important role for serotonergic (5-HT) modulation of the acoustic startle reflex (ASR) and prepulse inhibition (PPI). Acute challenge of brain serotonin by means of tryptophan depletion test (TDT) represents an established human challenge tool for temporary reduction of tryptophan (-TRP) levels and central nervous serotonin. Under these experimental conditions, PPI was found attenuated in males, but greater biochemical effects of TDT in the central nervous system of females are known. Therefore, in order to explore influence of 5-HT on various standard startle parameters in females, 16 young healthy females participated in a double-blind, cross-over TDT study. Acoustic stimuli were presented in 15 pulse-alone trials (100 dB, 40 ms) randomly followed by 25 pulse-alone or prepulse (70 dB, 30 ms; 120 ms interval) trials alongside electromyographic eyeblink recordings and mood state assessments. During 81% depletion of free plasma TRP, mean ASR magnitudes were significantly reduced compared to control (+TRP) condition while there were no differences in habituation or PPI nor did startle parameters correlate with mood states. Changes of plasma TRP and mood states correlated in tendency negatively in (-TRP) for depression and positively in (+TRP) for fatigue. In conclusion, this first study of startle parameters after TDT in a homogenous female population demonstrates that depletion of brain 5-HT in women only influences ASR.