Effectiveness of a digital lifestyle management intervention (levidex) to improve quality of life in people with multiple sclerosis: results of a randomized controlled trial.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory neurodegenerative disease with diverse symptomatology, significantly impacting patients' quality of life (QoL). While pharmacological therapies focus primarily on reducing inflammation and relapse rates, non-pharmacological interventions, including digital health applications, have shown promise in improving QoL among persons with MS (PwMS). Pilot studies had shown the feasibility and acceptability of levidex, a digital health application based on cognitive behavioral therapy (CBT) principles, a broad set of behavior change techniques, and relevant lifestyle-change advice. This randomized controlled trial aimed to examine the effects of levidex on MS-related QoL over 6 months. METHODS: Participants who were diagnosed with MS for at least one year were recruited via the internet in Germany, using a secure survey software platform, and were randomly assigned to the intervention group (IG), in which they received standard care + levidex, or an active control group (CG), in which they received standard care and were offered web-adapted material on the topic of lifestyle change from the German Multiple Sclerosis Society (DMSG). The primary outcome was MS-related QoL after 6 months, measured by the Hamburg Quality of Life Questionnaire in MS (HAQUAMS); secondary outcomes included QoL subscales, sick days, and health behavior, among others. Analyses of Covariance (ANCOVA) were used to examine intervention effects at 6 months. Participants were recruited between November 2020 and February 2022. RESULTS: A total of 421 adult participants (mean age: 47.5, 78.1% women) were included and randomized (IG, n = 195, CG, n = 226). After 6 months, the IG exhibited significantly higher MS-related QoL, compared to the CG (total score HAQUAMS, adjusted group mean difference = -0.14, 95% CI: [-0.22, -0.06], p = 0.001; Cohen's d = 0.23), with significant effects also observed on the cognitive and mood subscales. At 6 months, IG participants also reported significantly fewer sick days (median = 2 days in IG vs. 6 days in CG; W = 3939, p = 0.012) and significantly higher levels of daily activities, as measured by the Frenchay Activity Index, adjusted group mean difference = 1.37, 95% CI = [0.33, 2.40], p = 0.010; Cohen's d = 0.16. Safety analyses showed no adverse events and good satisfaction. CONCLUSIONS: Compared to the control group, levidex facilitated clinically relevant improvements in MS-related QoL, reduced sick days, and enhanced activity in PwMS over 6 months. These findings suggest that levidex can serve as an effective non-pharmacological adjunctive treatment element to standard care and could help improve QoL among PwMS. TRIAL REGISTRATION: Registered on 22.09.2020 at the German Clinical Trials Register DRKS00023023.

Efficacy of a cognitive-behavioral digital therapeutic on psychosocial outcomes in rheumatoid arthritis: randomized controlled trial.

Cognitive behavioral therapy improves psychosocial outcomes in rheumatoid arthritis (RA), but access is limited. We conducted a randomized controlled trial to evaluate the efficacy of a cognitive-behavioral digital therapeutic, reclarit, on psychosocial outcomes in adult RA patients with impaired health-related quality of life. Participants were randomized to reclarit plus treatment as usual (TAU) or TAU plus educational and informational material (active control). The primary outcome was SF-36 mental (MCS) and physical (PCS) component summary scores at 3 months, with additional assessments at 6 months. reclarit significantly improved SF-36 MCS scores compared to control (mean difference 3.3 [95% CI 0.7, 5.9]; p = 0.014), with high user satisfaction and sustained improvements at 6 months. Depression, anxiety, fatigue, and social/work functioning also improved significantly, while SF-36 PCS, pain, and disability scores did not differ. In conclusion, reclarit offers immediate, effective, evidence-based and personalized psychological support for RA patients.

Effectiveness of Predominantly Group Schema Therapy and Combined Individual and Group Schema Therapy for Borderline Personality Disorder: A Randomized Clinical Trial.

IMPORTANCE: Schema therapy (ST), delivered either in an individual or group format, has been compared with other active treatments for borderline personality disorder (BPD). To our knowledge, the 2 formats have not been compared with treatment as usual (TAU) or with each other. Such comparisons help determine best treatment practices. OBJECTIVE: To evaluate whether ST is more effectively delivered in a predominantly group or combined individual and group format and whether ST is more effective than optimal TAU for BPD. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, 3-arm randomized clinical trial conducted at 15 sites in 5 countries (Australia, Germany, Greece, the Netherlands, and the UK), outpatients aged 18 to 65 years who had BPD were recruited between June 29, 2010, and May 18, 2016, to receive either predominantly group ST (PGST), combined individual and group ST (IGST), or optimal TAU. Data were analyzed from June 4, 2019, to December 29, 2021. INTERVENTIONS: At each site, cohorts of 16 to 18 participants were randomized 1:1 to PGST vs TAU or IGST vs TAU. Both ST formats were delivered over 2 years, with 2 sessions per week in year 1 and the frequency gradually decreasing during year 2. Assessments were collected by blinded assessors. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in BPD severity over time, assessed with the Borderline Personality Disorder Severity Index (BPDSI) total score. Treatment retention was analyzed as a secondary outcome using generalized linear mixed model survival analysis. RESULTS: Of 495 participants (mean [SD] age, 33.6 [9.4] years; 426 [86.2%] female), 246 (49.7%) received TAU, 125 (25.2%) received PGST, and 124 (25.0%) received IGST (1 of whom later withdrew consent). PGST and IGST combined were superior to TAU with regard to reduced BPD severity (Cohen d, 0.73; 95% CI, 0.29-1.18; P < .001). For this outcome, IGST was superior to TAU (Cohen d, 1.14; 95% CI, 0.57-1.71; P < .001) and PGST (Cohen d, 0.84; 95% CI, 0.09-1.59; P = .03), whereas PGST did not differ significantly from TAU (Cohen d, 0.30; 95% CI, -0.29 to 0.89; P = .32). Treatment retention was greater in the IGST arm than in the PGST (1 year: 0.82 vs 0.72; 2 years: 0.74 vs. 0.62) and TAU (1 year: 0.82 vs 0.73; 2 years: 0.74 vs 0.64) arms, and there was no significant difference between the TAU and PGST arms (1 year: 0.73 vs 0.72; 2 years: 0.64 vs 0.62). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, IGST was more effective and had greater treatment retention compared with TAU and PGST. These findings suggest that IGST is the preferred ST format, with high retention and continuation of improvement in BPD severity after the completion of treatment. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2392.

Effectiveness and safety of the adjunctive use of an internet-based self-management intervention for borderline personality disorder in addition to care as usual: results from a randomised controlled trial.

IMPORTANCE: Borderline personality disorder (BPD) is a severe mental disorder that is often inadequately treated. OBJECTIVE: To determine if adding a self-management intervention to care as usual (CAU) is effective and safe. DESIGN: Randomised, controlled, rater-blind trial. Duration of treatment and assessments: 12 months. SETTING: Secondary care, recruited mainly via the internet. PARTICIPANTS: Patients with BPD and BPD Severity Index (BPDSI) of at least 15. INTERVENTIONS: CAU by treating psychiatrist and/or psychotherapist alone or adjunctive use of an internet-based self-management intervention that is based on schema therapy (priovi). MAIN OUTCOME MEASURE: Outcomes were assessed by trained raters. The primary outcome was change in BPDSI. The safety outcome was the number of serious adverse events (SAEs). The primary outcome time point was 12 months after randomisation. RESULTS: Of 383 participants assessed for eligibility, 204 were included (91.7% female, mean age: 32.4 years; 74% were in psychotherapy and 26% were in psychiatric treatment). The slope of BPDSI change did not differ significantly between groups from baseline to 12 months (F3,248= 1.857, p=0.14). At 12 months, the within-group effect sizes were d=1.38 (95% CI 1.07 to 1.68) for the intervention group and d=1.02 (95% CI 0.73 to 1.31) for the control group. The between-group effect size was d=0.27 (95% CI 0.00 to 0.55) in the intention-to-treat sample and d=0.39 (95% CI 0.09 to 0.68) for those who used the intervention for at least 3 hours (per-protocol sample). We found no significant differences in SAEs. CONCLUSIONS: We have not found a significant effect in favour of the intervention. This might be due to the unexpectedly large effect in the group receiving CAU by a psychiatrist and/or psychotherapist alone. TRIAL REGISTRATION: NCT03418142.

Looking at the bigger picture: Cortical volume, thickness and surface area characteristics in borderline personality disorder with and without posttraumatic stress disorder.

Borderline personality disorder (BPD) is a severe psychiatric disorder accompanied by multiple comorbidities. Neuroimaging studies have identified structural abnormalities in BPD with most findings pointing to gray matter volume reductions in the fronto-limbic network, although results remain inconsistent. Similar alterations were found in posttraumatic stress disorder (PTSD), a common comorbidity of BPD. Only a small number of studies have investigated structural differences in BPD patients regarding comorbid PTSD specifically and studies conducting additional surface analyses are scarce. We investigated structural differences in women with BPD with and without PTSD and non-patient controls. Automated voxel-based and region-based volumetric analyses were applied. Additionally, four surface-based measures were analyzed: cortical thickness, gyrification index, fractal dimension, and sulcus depth. Analyses did not identify cortical volume alterations in the fronto-limbic network. Instead, hypergyrification was detected in the right superior parietal cortex in BPD patients compared to non-patient controls. No distinction was revealed between BPD patients with and without PTSD. These findings underline the importance of a holistic investigation examining volumetric and surface measures as these might enhance the understanding of structural alterations in BPD.

Therapeutic Relationship in eHealth-A Pilot Study of Similarities and Differences between the Online Program Priovi and Therapists Treating Borderline Personality Disorder.

eHealth programs have been found to be effective in treating many psychological conditions. Regarding Borderline Personality Disorder (BPD), few programs have been tested; nevertheless, results are promising. The therapeutic alliance is an important factor predicting treatment outcome in BPD. However, we do not know yet to what extent BPD patients form a therapeutic alliance with an eHealth tool and how this relationship differs from the relationship with their human therapist. This study aims to address this question using priovi, an interactive schema therapy-based eHealth tool for BPD. Semi-structured interviews were conducted to explore how patients perceived the therapeutic alliance with priovi and its differences compared to the alliance with their human therapist (N = 9). Interview data were analyzed following the procedures of qualitative content analysis. Additionally, the Working Alliance Inventory (WAI-SR) was administered in two versions (regarding the human therapist and priovi, N = 16) every three months during the treatment phase of one year. Results indicate that patients were able to form a good therapeutic relationship with priovi, but it differed from the relationship to their human therapist. Important categories were "priovi is helpful, supportive and always there" and "priovi is less flexible". WAI ratings for the task subscale were high in both relationships but significantly higher in WAItherapist compared to WAIpriovi in two measurements (nine-months measurement: t = 2.76, df = 15, p = 0.015; twelve-months measurement: t = 3.44, df = 15, p = 0.004). These results indicate that BPD patients can form a functioning alliance with an eHealth program and that eHealth programs may be especially useful for psychoeducation and cognitive exercises.

Patients with borderline personality disorder and comorbid PTSD show biased attention for threat in the facial dot-probe task.

BACKGROUND AND OBJECTIVES: Biased attention to threat is likely to play a crucial role in the dysfunctional emotion-related information processing in borderline personality disorder (BPD). However, the role of comorbid posttraumatic stress disorder (PTSD) has not yet been fully disentangled. METHODS: BPD patients with (n = 24) and without (n = 46) PTSD, 35 patients with Cluster-C personality disorder and 52 non-patients participated in the facial dot-probe task with angry, happy and neutral faces during automatic (100 ms), controlled (600 ms), and later (1200 ms) stages of information processing. RESULTS: BPD patients showed a greater congruency effect to angry faces during the controlled stage of processing than controls. Specifically, in BPD with PTSD compared to controls, this effect was due to difficulties disengaging from threat, indicated by slower reaction times to incongruent angry targets compared to neutral trials. Regarding automatic and later stages of information processing, there was no attentional bias (AB) in BPD. None of the groups revealed biased attention for happy faces at any stages of information processing. LIMITATIONS: We did not include a control group of PTSD patients without BPD. Therefore, we cannot rule out that the present AB in BPD is mainly due to PTSD-specific psychopathology. CONCLUSIONS: These findings provide first evidence for an AB towards angry faces and difficulties disengaging from these threat-related social cues in adult BPD patients. Although BPD patients in general demonstrated an AB when compared with controls, this effect was especially pronounced for BPD with PTSD, suggesting a significant effect of trauma-related psychopathology on social attention in BPD.

Impulse control under emotion processing: an fMRI investigation in borderline personality disorder compared to non-patients and cluster-C personality disorder patients.

Impulsivity is a characteristic syndromal and neurobehavioral feature of borderline personality disorder (BPD). Research suggests an important interaction between high negative emotions and low behavioral inhibition in BPD. However, knowledge about the generalizability across stimulus categories and diagnosis specificity is limited. We investigated neural correlates of hypothesized impaired response inhibition of BPD patients to negative, positive and erotic stimuli, by comparing them to non-patients and cluster-C personality disorder patients. During fMRI scanning, 53 BPD patients, 34 non-patients and 20 cluster-C personality disorder patients completed an affective go/no-go task, including social pictures. BPD patients showed more omission errors than non-patients, independent of the stimulus category. Furthermore, BPD patients showed higher activity in the inferior parietal lobule and frontal eye fields when inhibiting negative versus neutral stimuli. Activity of the inferior parietal lobule correlated positively with the BPD checklist subscale impulsivity. When inhibiting emotional stimuli, BPD patients showed an altered brain activity in the inferior parietal lobe and frontal eye fields, whereas previously shown dysfunctional prefrontal activity was not replicated. BPD patients showed a general responsivity across stimulus categories in the frontal eye fields, whereas effects in the inferior parietal lobe were specific for negative stimuli. Results of diagnosis specificity support a dimensional rather than a categorical differentiation between BPD and cluster-C patients during inhibition of social emotional stimuli. Supported by behavioral results, BPD patients showed no deficiencies in emotionally modulated response inhibition per se but the present findings rather hint at attentional difficulties for emotional information.

Biased Attention to Facial Expressions of Ambiguous Emotions in Borderline Personality Disorder: An Eye-Tracking Study.

Preliminary evidence suggests that biased attention could be crucial in fostering the emotion recognition abnormalities in borderline personality disorder (BPD). We compared BPD patients to Cluster-C personality disorder (CC) patients and non-patients (NP) regarding emotion recognition in ambiguous faces and their visual attention allocation to the eyes. The role of comorbid posttraumatic stress disorder (PTSD) in BPD regarding emotion recognition and visual attention was explored. BPD patients fixated the eyes of angry/happy, sad/happy, and fearful/sad blends longer than non-patients. This visual attention pattern was mainly driven by BPD patients with PTSD. This subgroup also demonstrated longer fixations than CC patients and a trend towards longer fixations than BPD patients without PTSD for the angry/happy and fearful/sad blends. Emotion recognition was not altered in BPD. Biased visual attention towards the eyes of ambiguous facial expressions in BPD might be due to trauma-related attentional bias rather than to impairments in facial emotion recognition.

Imagery rescripting in individuals with binge-eating behavior: An experimental proof-of-concept study.

OBJECTIVE: Mental imagery is more strongly related to emotions than verbal cognitions. Binge eating is associated with dysfunctional emotional regulation. However, cognitive therapy techniques have focused on verbal cognitions. This proof-of-concept study compares a traditional cognitive therapy technique, cognitive restructuring (CR), with imagery rescripting (IR) in individuals with binge-eating disorder or bulimia nervosa. METHOD: Thirty-six participants were asked to recall an idiosyncratic mental image of social rejection. They were then randomly assigned to a single session of CR or IR. Ratings of positive and negative emotions, and impact on rational and emotional core beliefs were administered prior to and after imagery recall, after the experimental intervention, and 1 week later. Eating disorder psychopathology was measured before and 1 week after the experimental intervention. RESULTS: Repeated measures ANOVAs revealed that after the experimental intervention, negative emotions and core beliefs had significantly decreased in CR and IR. Both groups also showed an increase in positive emotions that lasted until 1-week follow-up. DISCUSSION: This study suggests that CR and IR as an experimental intervention have comparable impact on distress and rational and emotional core beliefs. The feasibility of IR has been demonstrated. The effect of imagery recall on CR needs further investigation.

A Schema Therapy-Based eHealth Program for Patients with Borderline Personality Disorder (priovi): Naturalistic Single-Arm Observational Study.

BACKGROUND: Electronic health (eHealth) programs have been found to be effective in treating many psychological conditions. However, regarding borderline personality disorder (BPD), only a few eHealth programs have been tested, involving small interventions based on the dialectical behavior therapy treatment approach. We investigated priovi, a program based on the schema therapy (ST) approach. priovi is considerably more comprehensive than prior programs, offering broad psychoeducation content and many therapeutic exercises. OBJECTIVE: We tested the acceptability and feasibility of priovi in 14 patients with BPD as an add-on to individual face-to-face ST. METHODS: Patients received weekly individual ST and used priovi over a period of 12 months. We assessed BPD symptom severity using self-reported and interview-based measures. Qualitative interviews were conducted with both patients and therapists to assess their experiences with priovi. RESULTS: BPD symptoms improved significantly (Cohen d=1.0). Overall, qualitative data showed that priovi was positively received by both patients and therapists. Some exercises provoked mild anxiety; however, no serious threat to safety was detected. CONCLUSIONS: priovi is a potentially helpful and safe tool that could support individual ST. It needs to be further tested in a randomized controlled study. TRIAL REGISTRATION: German Clinical Trials Register DRKS00011538; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00011538 (Archived by WebCite at http://www.webcitation.org/74jb0AgV8).

Schema therapy for borderline personality disorder: A qualitative study of patients' perceptions.

Schema therapy (ST) has been found to be effective in the treatment of borderline personality disorder (BPD). However very little is known about how the therapy is experienced by individuals with BPD including which specific elements of ST are helpful or unhelpful from their perspectives. The aim of this study is to explore BPD patients' experiences of receiving ST, in intensive group or combined group-individual format. Qualitative data were collected through semi-structured interviews with 36 individuals with a primary diagnosis of BPD (78% females) who received ST for at least 12 months. Participants were recruited as part of an international, multicenter randomized controlled trial (RCT). Interview data (11 Australian, 12 Dutch, 13 German) were analyzed following the procedures of qualitative content analysis. Patients' perceptions of the benefits gained in ST included improved self-understanding, and better awareness and management of their own emotional processes. While some aspects of ST, such as experiential techniques were perceived as emotionally confronting, patient narratives informed that this was necessary. Some recommendations for improved implementation of ST include the necessary adjunct of individual sessions to group ST and early discussion of therapy termination. Implications of the findings are also discussed, in particular the avenues for assessing the suitability of patients for group ST; management of group conflict and the optimal format for delivering treatment in the intensive group versus combined group-individual formats.

Protocol for the REVISIT-BPD Trial, a Randomized Controlled Trial Testing the Effectiveness of an Internet-Based Self-Management Intervention in the Treatment of Borderline Personality Disorder (BPD).

Introduction: Borderline Personality Disorder (BPD) is a prevalent condition that is often under-treated. This is partly because very few psychotherapists offer treatment for this disabling disorder. Internet-based self-management interventions could contribute to reducing the treatment gap but-mainly due to safety concerns-these have never been tested for BPD in controlled trials. Methods: Patients with BPD will be recruited primarily via the internet and randomized to two groups: care as usual (CAU) alone) or the self-management intervention priovi® in addition to CAU. At the end of the diagnostic interview, all participants will discuss an emergency plan. The main outcome measure is the clinician-rated symptom severity using the BPD Severity Index (BPDSI). Secondary outcome measures include a range of self-reported scales, an SCID-diagnosis of BPD and several safety parameters including serious adverse events (e.g., a life-threatening event, hospitalization or suicide attempt). Discussion: This trial will evaluate the effectiveness of the self-management intervention, priovi, in reducing symptoms of BPD. It will also assess the safety of its use in this target population. If successful, this intervention would be the first comprehensive internet intervention for the treatment of BPD and complement the wide range of internet interventions effective in treating other mental disorders, particularly depression and anxiety disorders. Trial Registration: NCT03418142 (clinicaltrials.gov) on January 23rd 2018. Trial status: recruiting, currently N = 108 (July 2018).

Neural correlates of intimate picture stimuli in females.

Jacob et al. (2011) previously reported on intimate picture stimuli for emotion research in females in Psychiatry Research. Difficulties to engage in intimate relations constitute problems of many mental disorders, and intimacy must be differentiated from pure sex drive. Functional neuroimaging is an important tool to understand the pathophysiology of psychiatric disorders. We now studied cerebral activation in response to intimate stimuli in 35 healthy women. Comparison stimuli were taken from the International Affective Picture System. Neuroimaging revealed increased activation in bilateral occipitotemporal, parietal and anterior cingulate cortices extending to the orbitofrontal area. These data reflect cognitive, emotional and motivational compounds congruent with previous neuroimaging data of attachment and long term romantic relationships. Lateral prefrontal, posterior insular regions and the fusiform face area were more active during control images. Our data present a solid basis for use in psychiatric samples.

Always on guard: emotion regulation in women with borderline personality disorder compared to nonpatient controls and patients with cluster-C personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity and impaired emotion regulation in patients with BPD. METHODS: During functional MRI (fMRI) scanning, patients with BPD, nonpatient controls and patients with cluster-C personality disorder completed an emotion regulation task, including negative, positive and erotic social pictures. RESULTS: We included 55 patients with BPD, 42 nonpatient controls and 24 patients with cluster-C personality disorder in our analyses. Passive viewing of negative stimuli resulted in greater activity in the anterior insula, temporoparietal junction and dorsolateral prefrontal cortex in patients with BPD than in nonpatient controls. The increased activity in the anterior insula and temporoparietal junction was also present when patients with BPD viewed positive stimuli. During regulation of negative stimuli compared with passive viewing, nonpatient controls showed greater activity in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and bilateral inferior parietal lobule. Patients with BPD did not show this increase in activity. LIMITATIONS: Findings cannot be generalized to men, and patients represented a heterogeneous group regarding comorbid diagnoses and medication. CONCLUSION: When looking at emotional stimuli, patients with BPD showed a unique pattern of activity, suggesting an increase in brain activity involved in emotion generation. In the case of negative stimuli this is accompanied by increased activity in regulation areas. In contrast, increase of regulation processes seems absent when patients with BPD are explicitly instructed to regulate. Results of diagnosis specificity support a dimensional rather than a dichotomous differentiation between BPD and cluster-C personality disorder regarding emotional sensitivity and emotional regulation of social stimuli.

Is It Possible to Enhance Intensity in Guided Imagery Exercises? An Experimental Study.

OBJECTIVE: Guided imagery exercises can have a powerful impact on distressing mental images. Clinically, it is usually recommended to experience these exercises as intensely as possible. However, patients sometimes object to the related instructions. In this study, we tested whether typical clinical instructions aiming at increasing intensity led to a stronger effect of the exercise. METHODS: Sixty-four healthy participants watched a trauma movie clip. Then they were pseudo-randomized into one of two strategies (intense, less intense) or a waiting control condition. Dependent variables were self-reported emotional intensity and psychophysiology measures. RESULTS: Participants in the intense ImRS strategy did not experience the exercise as more intense than those in the less intense ImRS strategy on any outcome measure. Both ImRS strategies showed increased sympathetic activation compared to a decrease of activation in the waiting control group. CONCLUSIONS: Our results suggest that emotional intensity in guided imagery exercises may not depend very much on the therapist's instructions.

Always on guard: emotion regulation in women with borderline personality disorder compared to nonpatient controls and patients with cluster-C personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity and impaired emotion regulation in patients with BPD. METHODS: During fMRI scanning, patients with BPD, nonpatient controls and patients with cluster-C personality disorder completed an emotion regulation task, including negative, positive and erotic social pictures. RESULTS: We included 55 patients with BPD, 42 nonpatient controls and 24 patients with cluster-C personality disorder in our analyses. Passive viewing of negative stimuli resulted in greater activity in the anterior insula, temporoparietal junction and dorsolateral prefrontal cortex in patients with BPD than in nonpatient controls. The increased activity in the anterior insula and temporoparietal junction was also present when patients with BPD viewed positive stimuli. During regulation of negative stimuli compared with passive viewing, nonpatient controls showed greater activity in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and bilateral inferior parietal lobule. Patients with BPD did not show this increase in activity. LIMITATIONS: Findings cannot be generalized to men, and patients represented a heterogeneous group regarding comorbid diagnoses and medication. CONCLUSION: When looking at emotional stimuli, patients with BPD showed a unique pattern of activity, suggesting an increase in brain activity involved in emotion generation. In the case of negative stimuli this is accompanied by increased activity in regulation areas. In contrast, increase of regulation processes seems absent when patients with BPD are explicitly instructed to regulate. Results of diagnosis specificity support a dimensional rather than a dichotomous differentiation between BPD and cluster-C personality disorder regarding emotional sensitivity and emotional regulation of social stimuli.

Deficient amygdala-prefrontal intrinsic connectivity after effortful emotion regulation in borderline personality disorder.

Emotion instability in borderline personality disorder (BPD) has been associated with an impaired fronto-limbic inhibitory network. However, functional connectivity (FC) underlying altered emotion regulation in BPD has yet to be established. Here, we used resting-state fMRI to investigate enduring effects of effortful emotion regulation on the amygdala intrinsic FC in BPD. In this multicenter study, resting-state fMRI was acquired before and after an emotion regulation task in 48 BPD patients and 39 non-patient comparison individuals. The bilateral amygdalae were used as a seed in the whole-brain FC analysis and two-way mixed ANOVA to test whether BPD patients exhibited weaker post-task increase in the amygdala intrinsic FC with the prefrontal cortex (PFC), compared to non-patients. Subsequently, we explored whether the results are common for personality disorders characterized by emotional problems, using additional data of 21 cluster-C personality disorder patients. In contrast to non-patients, BPD patients failed to show increased post-task amygdala resting-state FC with the medial, dorsolateral, ventrolateral PFC, and superior temporal gyrus, but surprisingly exhibited decreased FC with the posterior cingulate cortex and increased FC with the superior parietal lobule. In BPD patients, the emotion regulation task failed to increase resting-state amygdala FC with brain regions essential for effortful emotion regulation, which suggests: (a) altered cognitive control typically used to indirectly alleviate distress by reinterpreting the meaning of emotional stimuli; (b) impaired direct regulation of emotional responses, which might be common for personality disorders;