Vrije Universiteit Brussel Alterations in the fronto-limbic network and corpus callosum in borderline personality disorder

Neuroimaging research provides evidence of grey matter changes in the prefrontal-limbic network in borderline personality disorder (BPD), yet research scarcely examines the white matter (WM) within this circuitry. The present study aimed to explore WM in prefrontal-limbic brain networks within BPD. Quantitative diffusion tensor imaging (DTI-MRI) measures of fractional anisotropy (FA) and mean diffusion (MD) were used to analyze the neural pathways in fifteen individuals with BPD (M = 25, SD = 6.76), in comparison to thirteen healthy individuals (M = 27.92, SD = 8.41). Quantitative DTI-MRI measures of FA and MD were evaluated for the cingulum, the fornix, the corpus callosum (CC), the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF). Lower FA values for both the left and the right cingulum, the genu, body, and splenium of the CC, left ILF and right SLF were found in BPD, compared to healthy individuals. MD values were higher for the genu and splenium of the CC in BPD. The findings indicate that a large-scale emotional brain network is affected in BPD with alterations in MD and FA of WM prefrontal-limbic pathways of the heteromodal association cortex involved in emotion processing and emotion regulation. 1. Borderline personality disorder Borderline personality disorder (BPD) is a complex mental disorder characterized by instability across various life domains with a wide spectrum of characteristic symptoms including affective hyperreactivity, instability of the self-concept, emotional dysfunction, and difficulty in social relationships (Lieb, Zanarini, Schmahl, Linehan, & Bohus, 2004; Ninomiya et al., 2018; Skodol et al., 2002). The term borderline was introduced in 1953 by R.P. Knight and originated from the idea that some patients can be considered as balancing on the border between neurosis and psychosis. Its official use was finally established in the 1980s to be included among Axis II disorders in the DSM-III with the term ‘Borderline Personality Disorder’. Among the diagnostic criteria indicated in the Diagnostic and Statistical Manual of Mental Disorders, the Fifth Edition (DSM-5) (American Psychiatric Association (APA), 2001), BPD is characterised by a fragile self-structure that is easily disrupted and fragmented under stress, a weak identity, chronic feelings of emptiness and difficulty maintaining enduring intimate relationships. Intimate relationships easily elicit feelings of being misunderstood and even victimized with an enhanced fear of abandonment. BPD is commonly associated with disturbed emotion processing and emotion regulation reflected by rapidly changing, intense, unpredictable and reactive emotions, such as anxiety, anger or depressed feelings. Emotional hyperreactivity in BPD goes often together with different high-risk behaviors and deliberate acts of substance abuse, binge eating, self-harm, suicidal ideation, suicide attempts and high rates of suicide, affecting 1–2% of the general population and 15–20% in psychiatric settings (Lis, Greenfield, Henry, Guilé, & Dougherty, 2007). These behavioural responses occur alongside contexts with intense distress, anger episodes, dysphoria, and https://doi.org/10.1016/j.bandc. 2019.103596 Received 27 April 2017; Received in revised form 14 August 2019; Accepted 16 August 2019 ⁎ Corresponding author at: Research group of Biological Psychology, Clinical and Lifespan Psychology, Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium. Department of Clinical Studies and Imaging, Faculty of Medicine and Pharmacy, VUB, Brussels, Belgium E-mail address: Marie.Vandekerckhove@vub.be (M. Vandekerckhove). Brain and Cognition 138 (2020) 103596 Available online 23 December 2019 0278-2626/ © 2019 Elsevier Inc. All rights reserved. T feelings of abandonment (Samuel et al., 2012). Often preceded by an existence consisting of a damaging and traumatizing environment such as those with a lack of nurture, affection and high levels of parental denial, neglect but even massive, repeated or chronic physical, sexual and emotional abuse before adulthood (Zanarini et al., 2005). As such, adults with BPD often lack the skills needed to handle daily emotional stressful events, maintain stable relationships and to build a strong selfconcept and identity, resulting finally in distress intolerance and a variety of problematic behaviors to escape emotions such as by selfharm (Chapman, Specht, & Cellucci, 2005). As these familial, social and societal experiences (Pally, 2002), wires and shapes the human brain, it can readily cause invalidating transgenerational responses from future caregivers who do not teach the child how to adequately regulate one’s own emotions and may exacerbate an individual’s existing vulnerability when handling challenging daily emotional events (Linehan, 1993; Chapman, Dixon-Gordon & Walters, 2011). Also in a society of contingencies in which social and intergenerational problems increase while ties have weakened and unstable family contexts are increasing, ontological unsafety, and anxiety are fed. As a consequence, developmental psychobiological characteristics of this disorder has to be framed in light of pre-existing vulnerability and particularities of developmental influences in childhood, the society, lifestyle and cultural patterns of conduct. 2. Neuronal biomarkers of borderline personality disorder Despite rapidly growing literature focusing on abnormal developmental, behavioral, societal and neurophysiological constituents in BPD (Carrasco et al., 2012; Krause-Utz et al., 2014; Lischke et al., 2015; Mauchnik & Schmahl, 2010; New et al., 2013; Putnam & Silk, 2005), the developmental psychobiology and the pathogenesis underlying BPD remains complex and not well understood. Emerging techniques enhance insight and clarify disrupted functions such as neural pathways in BPD. Differential fine-grained advances in neuroscience and usage of biological indicators provide innovative opportunities to identify neurobiological underpinnings in BPD (Skodol et al., 2002). Parsing the relationship between BDP and associated neurophysiological circuits may help us further understand the underlying biological mechanisms implicated in this disorder and may help us treat it. Biological markers establishes external validators of diagnostic criteria and provide clues to etiological factors involved in BPD and options for treatment. BPD may be linked to abnormal brain anatomy, but little is known about possible impairments of the white matter microstructure in BPD. As individual variability is encoded neurophysiologically, it is plausible that personality disorders are not only correlated with specific neural grey matter (Selvaraj et al., 2012), but also with white matter correlates (Sprooten et al., 2011). However, research utilizing grey matter and diffusion tensor imaging (DTI) in adult BPD have been inconclusive.