The use of optical coherence tomography (OCT) and OCT angiography in borderline personality disorder compared to health control subjects.

BACKGROUND: Optical coherence tomography (OCT) or OCT angiography (OCTA) has been investigated in few research studies of psychiatric disorders. No research has been done using OCT or OCTA in patients with borderline personality disorder (BPD). METHODS: OCTA measured foveal avascular zone (FAZ), macular vessel density (MVD), and peripapillary vessel density (PVD). OCT measured the peripapillary retinal fiber layer (RNFL) and central retinal thickness (CRT). The study utilized the Ottawa Self-Injury Inventory, Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning (GAF) to assess the symptom characteristics of individuals with BPD. RESULTS: Fifty-nine eyes of BPD patients and 58 eyes of normal subjects were analyzed, MVD of the superficial retinal capillary plexus declined noticeably in most subfields (p < 0.05). Significant differences were observed in the whole inner ring and outer ring index between BPD and HC groups (p < 0.05). The patients with BPD exhibited lower RNFL and CRT, the difference was significant (p < 0.05). CRT indicated a significant negative correlation with the Ottawa Self-Injury Inventory (p < 0.05). In addition, we observed that there was a negative correlation identified between the MVD of the inner ring and HAMA (p < 0.05). Meanwhile, the MVD of the outer ring was positively correlated with GAF (p < 0.05). The areas under the receiver operating characteristic curves (AUROCs) for distinguishing BPD and HC eyes in OCTA were the highest for fovea MVD (0.679), followed by outer ring MVD (0.669), inner ring MVD (0.641), FAZ (0.579). In OCT, CRT was highest for BPD (0.711), followed by RNFL (0.625). CONCLUSION: The OCT and OCTA can non-invasively detect microvascular and morphology changes of the retina in BPD patients compared to healthy control subjects.

Amygdala functional connectivity in borderline personality disorder.

Borderline personality disorder (BPD) is characterised by structural and functional brain alterations. Yet, there is little data on functional connectivity (FC) across different levels of brain networks and parameters. In this study, we applied a multi-level approach to analyse abnormal functional connectivity. We analysed resting-state functional magnetic resonance imaging (fMRI) data sets of 69 subjects: 17 female BPD patients and 51 age-matched psychiatrically healthy female controls. fMRI was analysed using CONN toolbox including: a) seed-based FC analysis of amygdala connectivity, b) independent component analysis (ICA) based network analysis of intra- and inter-network FC of selected resting-state networks (DMN, SN, FPN), as well as c) graph-theory based measures of network-level characteristics. We show group-level seed FC differences with higher amygdala to contralateral (superior) occipital cortex connectivity in BPD, which correlated with schema-therapy derived measures of symptoms/traits across the entire cohort. While there was no significant group effect on DMN, SN, or FPN intra-network or inter-network FC, we show a significant group difference for local efficiency and cluster coefficient for a DMN-linked cerebellum cluster. Our findings demonstrate BPD-linked changes in FC across multiple levels of observation, which supports a multi-level analysis for future studies to consider different aspects of functional connectome alterations.

Effects of glabellar botulinum toxin injections on resting-state functional connectivity in borderline personality disorder.

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect.

Association of white matter microstructural alteration with non-suicidal self-injury behavior and visual working memory in adolescents with borderline personality disorder.

BACKGROUND: Non-suicidal self-injurious behavior (NSSI) is the core characteristic of adolescent borderline personality disorder (BPD) and visual working memory is involved in the pathological processes of BPD. This study aimed to investigate alterations in white matter microstructure and their association with NSSI and visual working memory in adolescents with BPD. METHODS: 53 adolescents diagnosed with BPD and 39 healthy controls (HCs) were enrolled. White matter microstructure was assessed with the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). Correlation analysis was performed to assess the association between FA/MD and core features of BPD. A mediation analysis was performed to test whether the effects of white matter alterations on NSSI could be mediated by visual working memory. RESULTS: Adolescents with BPD showed a reduced FA and an increased MD in the cortical-limbic and cortical-thalamus circuit when compared to the HCs (p < 0.05). Increased MD was positively correlated with NSSI, impulse control and identity disturbance (p < 0.05), and was negatively correlated with the score of visual reproduction. Reserved visual working memory masked the effects of white matter microstructural alterations on NSSI behavior. CONCLUSIONS: White matter microstructural deficits in the cortical-limbic and cortical-thalamus circuits may be associated with NSSI and visual working memory in adolescents with BPD. Reserved visual working memory may protect against NSSI.

Altered gray matter volume and functional connectivity in adolescent borderline personality disorder with non-suicidal self-injury behavior.

BACKGROUND AND OBJECTIVES: Non-suicidal self-injury (NSSI) behavior is one of the characteristics of borderline personality disorder (BPD) in adolescents. Prior studies have shown that adolescents with BPD may have a unique pattern of brain alterations. The purpose of this study was to investigate the alterations in brain structure and function including gray matter volume and resting-state functional connectivity in adolescents with BPD, and to assess the association between NSSI behavior and brain changes on neuroimaging in adolescents with BPD. METHODS: 53 adolescents with BPD aged 12-17 years and 39 age-gender matched healthy controls (HCs) were enrolled into this study. Brain magnetic resonance imaging (MRI) was acquired with both 3D-T1 weighted structural imaging and resting-state functional imaging. Voxel-based morphometry (VBM) analysis for gray matter volume and seed-based functional connectivity (FC) analysis were performed for assessing gray matter volume and FC. Clinical assessment for NSSI, mood, and depression was also obtained. Correlative analysis of gray matter alterations with self-injury or mood scales were performed. RESULTS: There were reductions of gray matter volume in the limbic-cortical circuit and default mode network in adolescents with BPD as compared to HCs (FWE P < 0.05, cluster size ≥ 1000). The diminished gray matter volumes in the left putamen and left middle occipital gyrus were negatively correlated with NSSI in adolescents with BPD (r = - 0.277 and P = 0.045, r = - 0.422 and P = 0.002, respectively). Furthermore, there were alterations of FC in these two regions with diminished gray matter volumes (voxel P < 0.001, cluster P < 0.05, FWE corrected). CONCLUSIONS: Our results suggest that diminished gray matter volume of the limbic-cortical circuit and default mode network may be an important neural correlate in adolescent BPD. In addition, the reduced gray matter volume and the altered functional connectivity may be associated with NSSI behavior in adolescents with BPD.

Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Neural correlates of aggression in personality disorders from the perspective of DSM-5 maladaptive traits: a systematic review.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in 2013, includes an alternative model of personality disorders (AMPD) focusing on a maladaptive trait model utilized to diagnose several personality disorders. Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are two conditions categorized by AMPD that exhibit high rates of violence and aggression. Several of the traits outlined in the AMPD, including hostility, impulsivity, risk-taking, and callousness, have been previously linked to aggression in BPD and ASPD. However, to the best of our knowledge, there has never been a synthesis of neuroimaging studies that have investigated links between these traits and aggression in BPD and ASPD. To overcome this gap, we conducted a systematic review under the PRISMA framework to locate neuroimaging articles published since the release of AMPD linking trait anger/hostility, impulsivity, risk-taking, and callousness to aggression in BPD and ASPD. Key findings included the following: i) anger/hostility, associated with alterations in the interplay between prefrontal and subcortical regions (primarily the amygdala), may be a common factor explaining aggressive reactions to response to interpersonal threat or provocation; ii) alterations of fronto-temporal-limbic regions and serotonergic and endocannabinoid signaling systems may link impulsivity to aggression in BPD and ASPD; iii) weaker cortico-striatal connectivity could relate to greater risk taking and greater proclivity for violence. Insufficient evidence from neuroimaging articles was discerned to describe a relationship between callousness and aggression. Overall, results of this review reveal a relative paucity of neuroimaging studies examining AMPD traits relevant to aggression in BPD and ASPD. In addition to encouraging further investigation of neuroimaging markers of AMPD traits linked to aggression, we recommend multi-methodological designs, including the incorporation of other biomarkers, such as hormones and indices of physiological arousal, to fully expand our understanding of aggression in BPD and ASPD.

Borderline shades: Morphometric features predict borderline personality traits but not histrionic traits.

Borderline personality disorder (BPD) is one of the most diagnosed disorders in clinical settings. Besides the fully diagnosed disorder, borderline personality traits (BPT) are quite common in the general population. Prior studies have investigated the neural correlates of BPD but not of BPT. This paper investigates the neural correlates of BPT in a subclinical population using a supervised machine learning method known as Kernel Ridge Regression (KRR) to build predictive models. Additionally, we want to determine whether the same brain areas involved in BPD are also involved in subclinical BPT. Recent attempts to characterize the specific role of resting state-derived macro networks in BPD have highlighted the role of the default mode network. However, it is not known if this extends to the subclinical population. Finally, we wanted to test the hypothesis that the same circuitry that predicts BPT can also predict histrionic personality traits. Histrionic personality is sometimes considered a milder form of BPD, and making a differential diagnosis between the two may be difficult. For the first time KRR was applied to structural images of 135 individuals to predict BPT, based on the whole brain, on a circuit previously found to correctly classify BPD, and on the five macro-networks. At a whole brain level, results show that frontal and parietal regions, as well as the Heschl's area, the thalamus, the cingulum, and the insula, are able to predict borderline traits. BPT predictions increase when considering only the regions limited to the brain circuit derived from a study on BPD, confirming a certain overlap in brain structure between subclinical and clinical samples. Of all the five macro networks, only the DMN successfully predicts BPD, confirming previous observations on its role in the BPD. Histrionic traits could not be predicted by the BPT circuit. The results have implications for the diagnosis of BPD and a dimensional model of personality.

Resting-state functional magnetic resonance imaging alterations in borderline personality disorder: A systematic review.

BACKGROUND: Borderline personality disorder (BPD) is a severe psychiatric disorder characterized by emotion dysregulation, impulsivity, and interpersonal disturbances. Several structural and functional neuroimaging abnormalities have been described in BPD. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) studies have recently suggested various connectivity alterations within and between large-scale brain networks in BPD. This review aimed at providing an updated summary of the evidence reported by the available rs-fMRI studies in BPD individuals. METHODS: A search on PubMed, Scopus, and Web of Science was performed to identify rs-fMRI alterations in BPD. A total of 15 studies met our inclusion criteria. RESULTS: Overall, aberrant resting-state functional connectivity (rs-FC) within and between default mode network (DMN), salience network (SN), and central executive network (CEN) were observed in BPD compared to healthy controls, as well as selective functional impairments in bilateral amygdala, anterior and posterior cingulate cortex, hippocampus, and prefrontal cortex. LIMITATIONS: The observational design, small sample size, prevalence of females, high rates of concurrent comorbidities and medications, and heterogeneity across imaging methodologies limit the generalizability of the results. CONCLUSIONS: The identification of altered patterns of rs-FC within and between selective brain networks, including DMN, SN, and CEN, could further our knowledge of the clinical symptoms of BPD, and therefore, future studies with multimodal methodologies and longitudinal designs are warranted to further explore the neural correlates of this disorder.

Childhood trauma and cortical thickness in healthy women, women with post-traumatic stress disorder, and women with borderline personality disorder.

BACKGROUND: Structural brain changes have been associated with childhood trauma (CT) and several trauma-associated mental disorders. It is not known whether specific brain alterations are rather associated with CT as such or with disorders that are common sequelae of CT. In this study, we characterized cortical thickness in three distinct groups with CT: healthy women (HC/CT), women with posttraumatic stress disorder (PTSD/CT) and women with borderline personality disorder (BPD/CT). These three CT-exposed groups were compared with healthy controls not exposed to CT (HC). METHODS: We recruited 129 women (n = 70 HC, n = 25 HC/CT, n = 14 PTSD/CT, and n = 20 BPD/CT) and acquired T1-weighted anatomical images. FreeSurfer was used for conducting whole-brain cortical thickness between-group comparisons, applying separate generalized linear models to compare cortical thickness of each CT-exposed group with HC. RESULTS: The HC/CT group had lower cortical thickness in occipital lobe areas (right lingual gyrus, left lateral occipital lobe) than the HC group. The BPD/CT group showed a broader pattern of reduced cortical thickness compared to the HC group, including the bilateral superior frontal gyrus, and bilateral isthmus, the right posterior, and left caudal anterior of the cingulate cortex as well as the right lingual gyrus of the occipital lobe. We found no differences between PTSD/CT and HC. CONCLUSIONS: Cortical thickness reduction in the right lingual gyrus of the occipital lobe seem to be related to CT but is also present in BPD patients even after adjusting for severity of CT. Possibly, reduced cortical thickness in the lingual gyrus presents a CT-related vulnerability factor for CT-related adult psychopathologies such as BPD. Reduced cortical thickness in the frontal and cingulate cortex may represent unique neuroanatomical markers of BPD possibly related to difficulties in emotion regulation.

Metacognitive interpersonal therapy in borderline personality disorder: Clinical and neuroimaging outcomes from the CLIMAMITHE study-A randomized clinical trial.

Different psychotherapeutic approaches demonstrated their efficacy but the possible neurobiological mechanism underlying the effect of psychotherapy in borderline personality disorder (BPD) patients is poorly investigated. We assessed the effects of metacognitive interpersonal therapy (MIT) on BPD features and other dimensions compared to structured clinical management (SCM). We also assessed changes in amygdala activation by viewing emotional pictures after psychotherapy. One hundred forty-one patients were referred and 78 BPD outpatients were included and randomized to MIT or SCM. Primary outcome was emotional dysregulation assessed with the Difficulties in Emotion Regulation Scale (DERS). We also assessed BPD symptomatology, number of PD criteria, metacognitive abilities, state-psychopathology, depression, impulsiveness, interpersonal functioning, and alexithymia. A subset of 60 patients underwent functional magnetic resonance imaging before and after 1 year of psychotherapy to assess amygdala activation by viewing standardized emotional pictures (secondary outcome). DERS scores decreased in both groups (time effect p < .001). The Cohen's d effect size for change (baseline posttreatment) on DERS was very large (d = 0.84) in MIT, and large (d = 0.76) in SCM. Both groups significantly improved in depressive symptoms, state-psychopathology, alexithymia, and interpersonal functioning. MIT showed larger effect on metacognitive functions than SCM (Time × Group p < .001). Both interventions showed a significant effect on BPD symptomatology although SCM group showed a larger decrease. On the contrary, MIT group showed larger decrease in impulsivity and number of PD criteria. Interestingly, both MIT and SCM modulated amygdala activation in BPD patients. MIT is a valid and effective psychotherapy for BPD with an impact on amygdala activation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Alteration of surface morphology and core features in adolescents with borderline personality disorder.

BACKGROUND: Accurate early diagnosis of adolescent borderline personality disorder (BPD) is critical for prompt treatment. The aim of this study was to assess the alteration of brain surface morphology and to evaluate its relationship with core features in adolescent BPD. METHODS: A total of 52 adolescents with BPD aged 12-17 years and 39 age- and sex-matched healthy controls (HCs) were prospectively enrolled into the study. Brain magnetic resonance imaging (MRI) was obtained with both 3D-T1 weighted structural sequence and resting-state functional data. The structural data was analyzed for surface morphology parameters including the local gyrification index (LGI), mean curvature and surface area. The functional MRI data was analyzed for seed-based functional connectivity (FC). Correlative analysis of surface morphology and core features of adolescent BPD was performed. RESULTS: Adolescents with BPD showed the following altered surface morphology in the limbic-cortical circuit when compared to the HCs: (1) reduced LGI in the left fusiform and right superior temporal gyrus; (2) reduced mean curvature in the left precentral gyrus and right rostral anterior cingulate cortex, and increased mean curvature in the bilateral pericalcarine; and (3) reduced surface area in the left paracentral gyrus, left pars triangularis, right insula and right lateral orbitofrontal gyrus (P < 0.05, FWE correction). In addition, these brain regions with altered surface morphology were significantly correlated with several core features including the mood instability, self-identity problems, and non-suicidal self-injury behavior in adolescents with BPD (P < 0.05). Furthermore, there was enhanced functional connectivity among these altered brain regions within the limbic-cortical circuit (voxel P < 0.001, cluster P < 0.05, FWE corrected). CONCLUSIONS: Adolescents with BPD had significant alterations of brain surface morphology in the limbic-cortical circuit, which was correlated with core BPD features. These results implicated the surface morphology parameters and FC alterations may potentially serve as neuroimaging biomarkers for adolescents with BPD.

Altered cortical thickness and emotional dysregulation in adolescents with borderline personality disorder.

Background: Emotional dysregulation is a core feature of borderline personality disorder (BPD). Previous studies have reported that abnormal grey matter volume is associated with the limbic-cortical circuit and default mode network (DMN) in patients with BPD. However, alterations of cortical thickness in adolescents with BPD have not been well evaluated.Objective: The aim of this study was to assess cortical thickness and its association with emotional dysregulation in adolescents with BPD.Method: This prospective study enrolled 52 adolescents with BPD and 39 age- and sex-matched healthy controls (HCs). Assessments included brain magnetic resonance imaging (MRI) acquisition with structural and resting-state functional MRI data, and clinical assessment for emotional dysregulation using the Difficulties in Emotion Regulation Scale (DERS). Cortical thickness and seed-based functional connectivity were analysed with FreeSurfer 7.2 software. Correlation analysis between cortical thickness and the scores from emotional assessment was performed with Spearman analysis.Results: Compared to HCs, there was altered cortical thickness in the DMN and limbic-cortical circuit in adolescents with BPD (Monte Carlo correction, all p < .05). These regions with altered cortical thickness were significantly associated with emotional dysregulation (all p < .05). There were also alterations of functional connectivity, i.e. with increased connectivity of the right prefrontal cortex with bilateral occipital lobes, or with the limbic system, and with decreased connectivity among the DMN regions (voxel p < .001, cluster p < .05, family-wise error corrected).Conclusions: Our results suggest that the altered cortical thickness and altered functional connectivity in the limbic-cortical circuit and DMN may be involved in emotional dysregulation in adolescents with BPD.

Emotional dysregulation is a core feature of borderline personality disorder, but the underlying neural correlates are not well known.There was altered cortical thickness and functional connectivity in the DMN and limbic­cortical circuit in adolescents with borderline personality disorder.Altered cortical thickness was associated with emotional dysregulation in adolescents with borderline personality disorder.

The Neuropsychological Mechanisms of Treatment of Bipolar Disorder and Borderline Personality Disorder: Activation Likelihood Estimation Meta-Analysis of Brain Imaging Research.

Objective: To explore the alteration of brain regions after treatments for bipolar disorder (BD) and borderline personality disorder (BPD) in order to discover the underlying neural mechanisms of therapies.Data Sources: An electronic search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception until June 2021 was conducted.Study Selection: Articles reporting the results of changes in brain activation after treatment, to assess the effects of therapy relative to a before-treatment condition, were included. A total of 1,592 records were retrieved, with 34 studies ultimately included.Data Extraction: Activation coordinates were extracted from each study. We used activation likelihood estimation meta-analysis to evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.Results: Most brain regions with abnormal activation were improved after treatments for BD and BPD. The brain activity changes produced by psychotherapy were mostly in the frontal areas, while drug therapy primarily impacted the limbic areas. In BD, treatments were associated with activation alterations in the inferior frontal gyrus, superior temporal gyrus, and cingulate gyrus, while in BPD, treatments were associated with activation alterations in the supramarginal gyrus, middle frontal gyrus, and parahippocampal gyrus.Conclusions: These results suggest that drug therapy might have a bottom-up effect, while psychotherapy might have a top-down effect. This study may contribute to the clinical prediction of treatment efficacy in BD and BPD and to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Dissociation of basolateral and central amygdala effective connectivity predicts the stability of emotion-related impulsivity in adolescents and emerging adults with borderline personality symptoms: a resting-state fMRI study.

BACKGROUND: Borderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents and emerging adults. Here, we examined the contribution of fronto-limbic effective connectivity (EC) to the longitudinal stability of emotion-related impulsivity, a key feature of BPD, in symptomatic adolescents and young adults. METHODS: We compared resting-state EC in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13-30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We examined the association of directed centrality metrics with initial levels and rates of change in emotion-related impulsivity symptoms over a one-year follow-up using latent growth curve models (LGCMs). RESULTS: In controls, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS, respectively. In the BPD group, bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs indicated that emotion-related impulsivity was stable across a one-year follow-up in the BPD group. Further, higher EC of R CeN to other regions in controls was associated with stronger within-person decreases in emotion-related impulsivity. CONCLUSIONS: Functional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents and young adults, BLA may predominate over CeN activity, while in controls the ability of CeN to influence BLA activity predicted more rapid reductions in emotion-related impulsivity.

Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Effects of pharmacological treatments on neuroimaging findings in borderline personality disorder: A review of FDG-PET and fNIRS studies.

BACKGROUND: Borderline personality disorder (BPD) is a serious mental condition characterized by instability in identity, interpersonal relationships, emotion regulation and impulsivity. These symptoms seem to be associated to specific brain alterations, which have been largely investigated. In particular, positron emission tomography (PET) and functional near-infrared spectroscopy (fNIRS) have demonstrated abnormalities in brain metabolism and hemodynamics in BPD, specifically in the fronto-limbic system. However, the role of medications on brain metabolism and hemodynamics in BPD is still largely unknown. METHODS: We conducted a search on PubMed, Scopus and Web of Science of PET and fNIRS studies exploring the effect of medications on brain metabolism and hemodynamics in BPD. A total of 10 studies met the inclusion criteria. RESULTS: Overall, PET studies showed an effect of psychotropic agents on brain metabolism, especially in frontal and temporal areas. Also, higher metabolic rates in frontal areas were found to correlate with clinical improvements. In contrast, fNIRS investigations reported an inconclusive or absent effects on brain hemodynamics in BPD patients. LIMITATIONS: The small sample size, the elevated percentage of women, the heterogeneity in pharmacological agents and the presence of comorbidities limit the conclusions of the present review. CONCLUSIONS: Serotoninergic agents and second-generation antipsychotics produce changes in frontal and temporal metabolism in BPD, which appear to correlate with clinical improvements. Differently, brain hemodynamics do not seem to be significantly affected by the most commonly prescribed drugs in BPD, suggesting that the therapeutic actions of medications are not mediated by changes in neural hemodynamics.

Common and distinct patterns of gray matter alterations in young adults with borderline personality disorder and major depressive disorder.

Young adults with borderline personality disorder (BPD) and major depressive disorder (MDD) have a relatively high comorbidity rate; however, whether they share a neurobiological basis remains controversial. Although previous studies have reported respective brain alterations, the common and distinct gray matter changes between two disorders are still inconsistent. We conducted a meta-analysis using anisotropic effect size-based algorithms (ASE-SDM) to identify consistent findings from whole-brain voxel-based morphometry (VBM) studies of gray matter volume (GMV) in 274 young adults (< 45 years old) with BPD and 1576 with MDD. Compared with healthy controls, the young adults with BPD showed GMV reduction mainly in the prefrontal cortex including the inferior frontal gyrus and superior frontal gyrus, medial temporal network, and insula, whereas the MDD showed GMV alteration in the visual network (fusiform gyrus and inferior temporal gyrus), sensorimotor network (bilateral postcentral gyrus (PoCG) and right cerebellum) and left caudate nucleus. The GMV differences between these two disorders were concentrated in the left orbitofrontal cortex, cingulate cortex, right insula, and cerebellum. The meta-regression of the MDD group showed a negative association between disease duration and the right middle cingulate gyrus as well as negative associations between depressive symptoms and brain regions of the right cerebellum and the left PoCG. Our results identified common and distinct patterns of GMV alteration between BPD and MDD, which may provide neuroimage evidence for the disorder comorbidity mechanisms and partly indicate the similar and different biological features in emotion regulation of the two disorders. This study was registered with PROSPERO (CRD42020212758).

Voice Hearing in Borderline Personality Disorder Across Perceptual, Subjective, and Neural Dimensions.

BACKGROUND: Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as "pseudohallucinations," but they nevertheless have a detrimental impact on well-being. METHODS: The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively. RESULTS: Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level-dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices. CONCLUSION: In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as "pseudohallucinations." These highlight a need to reconsider this experience as a treatment priority.