Self-relevant disgust and self-harm urges in patients with borderline personality disorder and depression: a pilot study with a newly designed psychological challenge.

BACKGROUND: Borderline personality disorder (BPD) is a common psychiatric condition associated with self-harm. Self-harm is poorly understood and there is currently no treatment for acute presentations with self-harm urges. OBJECTIVES: By using a new task (Self-relevant Task; SRT), to explore emotions related to one's own person (PERSON task) and body (BODY task), to study the correlations of these emotions, specifically disgust, with self-harm urge level changes, and to test the task's potential to be developed into an experimental model of self-harming for treatment trials. METHODS: 17 BPD patients, 27 major depressive disorder (MDD) patients, and 25 healthy volunteers performed the SRT. Emotion labels were extracted from task narratives and disgust and self-harm urge level changes measured by visual analogue scales. We used validated rating scales to measure symptom severity. RESULTS: The SRT was effective at inducing negative emotions and self-harm urge changes. Self-harm urge changes correlated with borderline symptom severity. Post-task disgust levels on the visual analogue scales were higher in BPD patients than in healthy controls in the PERSON task, and higher than in both control groups in the BODY task. Changes in disgust levels during the task were significantly greater in the patient groups. Post-task disgust levels or changes in disgust were not associated with self-harm urge changes (except the latter in MDD in the PERSON task), but self-harm urge changes and disgust (but no other emotion) narrative labels were on a whole sample level. CONCLUSION: Although associations with the analogue scale measures were not significant, self-disgust reported in the narrative of patients may be associated with a higher probability of self-harm urges. Further research with larger sample sizes is needed to confirm this relationship and to examine whether reducing self-disgust could reduce self-harm urges. The SRT was effective and safe, and could be standardized for experimental studies.This work was partly funded by a Core Award from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). Sawsan Abdul-Hamid received a grant from the Evelyn Trust to help to cover the costs of her research placement with the research group. The Talisman Trust also supported the study with a grant.This is the final published version, which can also be found on the PLoS website here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0099696#ac

Brain structural signatures of negative symptoms in depression and schizophrenia.

Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.This work was supported by Brain and Behavior Research Foundation (NARSAD) and Medical Research Council (MRC) awards to GKM, and by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute, University of Cambridge. We thank Dr. Zheng Ye for her help with image analysis and technical support, Niels Reinders and staff at the Wolfson Brain Imaging Centre for help with data collection, and staff at IAPT, CAMEO and the Rehabilitation and Recovery Service in the Cambridgeshire and Peterborough NHS Foundation Trust for help with recruitment. The study was supported by infrastructure provided by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute at the University of Cambridge.This is the final version published by Frontiers here: http://journal.frontiersin.org/Journal/10.3389/fpsyt.2014.00116/abstract

The overlap between autistic spectrum conditions and borderline personality disorder

BACKGROUND: Both people with autism spectrum conditions (ASC) and borderline personality disorder (BPD) are significantly challenged in terms of understanding and responding to emotions and in interpersonal functioning. AIMS: To compare ASC, BPD, and comorbid patients in terms of autistic traits, empathy, and systemizing. METHODS: 624 ASC, 23 BPD, and 16 comorbid (ASC+BPD) patients, and 2,081 neurotypical controls (NC) filled in the Autism Spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient-Revised (SQ-R). RESULTS: On the AQ, the ASC group scored higher than the BPD group, who in turn scored higher than the comorbid group, who scored higher than controls. On the EQ, we found the comorbid and ASC groups scored lower than the BPD group, who were not different from controls. Finally, on the SQ-R, we found the ASC and BPD group both scored higher than controls. CONCLUSIONS: Similar to ASC, BPD patients have elevated autistic traits and a strong drive to systemize, suggesting an overlap between BPD and ASC.The authors were supported by the Autism Research Trust and the MRC during the period of this work. The research was also supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding.

In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.Supported by the Wellcome Trust Institutional Strategic Support Fund [097814/Z/11], a MRC Clinician Scientist [G0701911], a Brain and Behavior Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council [G1000183]and Wellcome Trust [093875/Z/10/Z]; by awards from the Wellcome Trust [095692] and the Bernard Wolfe Health Neuroscience Fund to Dr. Fletcher, and by the Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fpsyg.2015.0128

Hedonic and disgust taste perception in borderline personality disorder and depression.

Depression and borderline personality disorder (BPD) are both thought to be accompanied by alterations in the subjective experience of environmental rewards. We evaluated responses in women to sweet, bitter and neutral tastes (juice, quinine and water): 29 with depression, 17 with BPD and 27 healthy controls. The BPD group gave lower pleasantness and higher disgust ratings for quinine and juice compared with the control group; the depression group did not differ significantly from the control group. Juice disgust ratings were related to self-disgust in BPD, suggesting close links between abnormal sensory processing and self-identity in BPD.Supported by the Wellcome Trust [093875/Z/10/Z], [097814/Z/11], [095692]; Medical Research Council [G0701911], [G1000183]; Isaac Newton Trust, Cambridgeshire and Peterborough NHS Foundation Trust, Talisman Trust, University of Cambridge, and the NIHR Cambridge Biomedical Research Centre.This is the final version. It was first published by the Royal College of Psychiatrists at http://bjp.rcpsych.org/content/207/1/79.lon

Amygdala and dlPFC abnormalities, with aberrant connectivity and habituation in response to emotional stimuli in females with BPD

Background: Little is known about the frontolimbic abnormalities thought to underlie borderline personality disorder (BPD). We endeavoured to study regional responses, as well as their connectivity and habituation during emotion processing. Methods: 14 BPD patients and 14 normal female controls (NC) controlled for menstrual phase underwent emotion-induction during an fMRI task using standardised images in a block design. We then performed psychophysiological interaction (PPI) analysis to investigate functional connectivity. Results: BPD patients reported more disgust in questionnaires compared to controls. Relative to NC, they showed reduced left amygdala and increased dorsolateral prefrontal cortex (dlPFC) activation to all emotions collapsed versus neutral. Habituation of ventral striatal activity to repeated emotional stimuli was observed in controls but not in BPD. Finally, in the context of disgust (but not other emotions) versus neutral, BPD patients displayed enhanced left amygdala coupling with the dlPFC and ventral striatum. Limitations: Strict inclusion criteria reduced the sample size. Conclusions: In summary, BPD showed abnormal patterns of activation, habituation and connectivity in regions linked to emotion regulation. Amygdala deactivation may be mediated by abnormal top-down regulatory control from the dorsolateral prefrontal cortex. Aberrant emotion processing may play a unique role in the pathophysiology of BPD

Oscillatory underpinnings of mismatch negativity and their relationship with cognitive function in patients with schizophrenia.

BACKGROUND: Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia. METHOD: 21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning. RESULTS: Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance. CONCLUSION: The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.Organismic and Evolutionary Biolog