Emotion dysregulation, impulsivity and anger rumination in borderline personality disorder: the role of amygdala and insula

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Borderline Personality Disorder (BPD) is a severe mental disorder, characterized by deficits in emotion regulation, interpersonal dysfunctions, dissociation and impulsivity. Brain abnormalities have been generally explored; however, the specific contribution of different limbic structures to BPD symptomatology is not described. The aim of this study is to cover this gap, exploring functional and structural alterations of amygdala and insula and to highlight their contribution to neuropsychiatric symptoms. Twenty-eight BPD patients (23.7 ± 3.42 years; 6 M/22F) and twenty-eight matched healthy controls underwent a brain MR protocol (1.5 T, including a 3D T1-weighted sequence and resting-state fMRI) and a complete neuropsychiatric assessment. Volumetry, cortical thickness and functional connectivity of amygdala and insula were evaluated, along with correlations with the neuropsychiatric scales. BPD patients showed a lower cortical thickness of the left insula (p = 0.027) that negatively correlated with the Anger Rumination Scale (p = 0.019; r = − 0.450). A focused analysis on female patients showed a significant reduction of right amygdala volumes in BPD (p = 0.037), that correlate with Difficulties in Emotion Regulation Scale (p = 0.031; r = − 0.415), Beck Depression Inventory (p = 0.009; r = − 0.50) and Ruminative Response Scale (p = 0.045; r = − 0.389). Reduced functional connectivity was found in BPD between amygdala and frontal pole, precuneus and temporal pole. This functional connectivity alterations correlated with Anger Rumination Scale (p = .009; r = − 0.491) and Barratt Impulsiveness Scale (p = 0.020; r = − 0.447). Amygdala and insula are altered in BPD patients, and these two limbic structures are implicated in specific neuropsychiatric symptoms, such as difficulty in emotion regulation, depression, anger and depressive rumination.Peer reviewe

Converging Medial Frontal Resting State and Diffusion Based Abnormalities in Borderline Personality Disorder

Background The psychological profile of patients with borderline personality disorder (BPD), with impulsivity and emotional dysregulation as core symptoms, has guided the search for abnormalities in specific brain areas such as the hippocampal-amygdala complex and the frontomedial cortex. However, whole-brain imaging studies so far have delivered highly heterogeneous results involving different brain locations. Methods Functional resting-state and diffusion magnetic resonance imaging data were acquired in patients with BPD and in an equal number of matched control subjects (n = 60 for resting and n = 43 for diffusion). While mean diffusivity and fractional anisotropy brain images were generated from diffusion data, amplitude of low-frequency fluctuations and global brain connectivity images were used for the first time to evaluate BPD-related brain abnormalities from resting functional acquisitions. Results Whole-brain analyses using a p = .05 corrected threshold showed a convergence of alterations in BPD patients in genual and perigenual structures, with frontal white matter fractional anisotropy abnormalities partially encircling areas of increased mean diffusivity and global brain connectivity. Additionally, a cluster of enlarged amplitude of low-frequency fluctuations (high resting activity) was found involving part of the lefthippocampus and amygdala. In turn, this cluster showed increased resting functional connectivity with theanterior cingulate. Conclusions With a multimodal approach and without using a priori selected regions, we prove that structural and functional abnormality in BPD involves both temporolimbic and frontomedial structures as well as their connectivity. These structures have been previously related to behavioral and clinical symptoms in patients with BPD

Functional and Structural MRI Studies on Impulsiveness: Attention-Deficit/Hyperactive Disorder and Borderline Personality Disorders

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Women with early maltreatment experience show increased resting-state functional connectivity in the theory of mind (ToM) network

Background: Experience of childhood maltreatment significantly increases the risk for the development of psychopathology and is associated with impairments in socio-cognitive skills including theory-of-mind (ToM). In turn, neural alterations in ToM processing might then influence future interpersonal interaction and social-emotional understanding. Objective: To assess resting-state activity in the theory-of-mind network in traumatized and non-traumatized persons. Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporo-parietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus). Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. Number of types of abuse was driving the effect for the temporo-parietal junction and the brainstem, while the severity of abuse was linked to increased RSFC between the middle temporal gyrus and the frontal cortex. Post-hoc analyses of brainstem regions indicated the involvement of the serotonergic system (dorsal raphe). Conclusions: The data indicate a lasting impact of childhood maltreatment on the neural networks involved in social information processing that are integral to understanding others' emotional states. Indeed, such altered neural networks may account for some of the interpersonal difficulties victims of childhood maltreatment experience

Mechanisms of disturbed emotion processing and social interaction in borderline personality disorder: state of knowledge and research agenda of the German Clinical Research Unit

The last two decades have seen a strong rise in empirical research in the mechanisms of emotion dysregulation in borderline personality disorder. Major findings comprise structural as well as functional alterations of brain regions involved in emotion processing, such as amygdala, insula, and prefrontal regions. In addition, more specific mechanisms of disturbed emotion regulation, e.g. related to pain and dissociation, have been identified. Most recently, social interaction problems and their underlying neurobiological mechanisms, e.g. disturbed trust or hypersensitivity to social rejection, have become a major focus of BPD research. This article covers the current state of knowledge and related relevant research goals. The first part presents a review of the literature. The second part delineates important open questions to be addressed in future studies. The third part describes the research agenda for a large German center grant focusing on mechanisms of emotion dysregulation in BPD

Activation and Habituation of the Cingulate Cortex during Emotion Processing in Healthy Controls, Borderline, and Schizotypal Personality Disorder

Disturbances in emotional functioning are central features of the clinical profiles of both borderline and schizotypal personality disorder (BPD and SPD, respectively). BPD is characterized by a high sensitivity to emotional stimuli and unusually strong and long-lasting reactions, indicative of impaired habituation to emotional stimuli (Linehan, 1993). Previous research suggests that SPD patients demonstrate limbic hyper-reactivity to unpleasant stimuli, at least initially, but intact habituation to repeated presentation of unpleasant stimuli (Hazlett et al., 2012). The cingulate cortex supports various aspects of emotion processing and regulation, and abnormalities of this region have been related to emotion dysfunction in SPD and BPD (Koenigsberg, Fan, et al., 2009; Modinos, Ormel, & Aleman, 2010). However, findings of functional cingulate abnormalities in the context of emotion processing have been inconsistent in BPD and limited in SPD. The current study utilized event-related functional magnetic resonance imaging (fMRI) in three groups, BPD patients, SPD patients, and healthy control individuals, during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures, each presented twice within their respective trial. This approach permitted the examination of reactivity to emotional stimuli and habituation of emotional responses within the cingulate. Blood-oxygen-level dependent response values were obtained within the manually delineated anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) and compared across groups. Compared to healthy controls and SPD patients, BPD patients exhibited significantly greater activity in the ACC during the presentation of neutral pictures. Heightened activity in the BPD group persisted across the initial and repeated presentations of neutral pictures. On the other hand, SPD patients exhibited greater activity in the ACC compared to healthy controls and BPD patients during the initial presentation of unpleasant pictures, but activity normalized when the pictures were repeated. The two patient groups demonstrated heightened ACC activation, but these abnormalities were differentiated by associated picture-type (neutral versus unpleasant) and attenuation of the response upon repeated presentation of the stimuli. Diagnostic differences in PCC activation did not reach significance. Overall results suggest unique involvement of the ACC in BPD and SPD symptomatology

Repetitive Transcranial Magnetic Stimulation Treating Impulsivity in Borderline Personality Disorder and Attention Deficit/Hyperactivity Disorder

The need for novel treatment approaches that target impulsivity symptoms in neuropsychiatric disorders is clear. Repetitive transcranial magnetic stimulation (rTMS) allows selective neuromodulation of regions involved in the functional neuroanatomy of neuropsychiatric disorders. This chapter presents impulsivity in psychiatry, especially in borderline personality disorder (BPD) and attention-deficit hyperactivity disorder (ADHD), its neural underpinnings, and its possible treatment by rTMS. We reviewed available studies on rTMS in impulsivity in BPD and ADHD published before August 13, 2017, systematically searching in the PubMed, Web of Science, and Scopus databases. The results are discussed in the context of the latest neuropsychological models of impulsivity and their underlying functional neuroanatomy. rTMS treatment of impulsivity in BPD and ADHD seems to be a plausible approach. The functional neuroanatomy of processes related to impulsive behavior and decision making in these disorders is linked with abnormalities in the fronto-limbic structures that can be targeted and modulated by rTMS. Although limited evidence is available, rTMS seems to be a safe and potentially effective method of impulsivity treatment in patients with BPD and ADHD. However, more studies are needed to determine the most efficient cortical location and design for rTMS treatment of impulsivity

Integrating Preclinical and Clinical Models of Negative Urgency

Overwhelming evidence suggests that negative urgency is robustly associated with rash, ill-advised behavior, and this trait may hamper attempts to treat patients with substance use disorder. Research applying negative urgency to clinical treatment settings has been limited, in part, due to the absence of an objective, behavioral, and translational model of negative urgency. We suggest that development of such a model will allow for determination of prime neurological and physiological treatment targets, the testing of treatment effectiveness in the preclinical and the clinical laboratory, and, ultimately, improvement in negative-urgency-related treatment response and effectiveness. In the current paper, we review the literature on measurement of negative urgency and discuss limitations of current attempts to assess this trait in human models. Then, we review the limited research on animal models of negative urgency and make suggestions for some promising models that could lead to a translational measurement model. Finally, we discuss the importance of applying objective, behavioral, and translational models of negative urgency, especially those that are easily administered in both animals and humans, to treatment development and testing and make suggestions on necessary future work in this field. Given that negative urgency is a transdiagnostic risk factor that impedes treatment success, the impact of this work could be large in reducing client suffering and societal costs

Understanding Brain Mechanisms of Reactive Aggression

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