Mismatch negativity in treatment-resistant depression and borderline personality disorder

Objective

Cognitive dysfunctions, such as attentional impairment, are central features of both treatment-resistant depression (TRD) and borderline personality disorder (BPD). The treatment failure of TRD due to its comorbidity with BPD is debated in the literature. The mismatch negativity (MMN) of the event-related potentials provides an objective marker of involuntary stimulus selective processing, which might help shed light on this issue and provide an avenue for investigating a possible endophenotypic marker for TRD.

Method

We investigated MMN in 22 patients with TRD, 19 with BPD, and 22 with TRD cormorbid with BPD (TRD + BPD), as well as in 32 healthy volunteers, by employing an acoustic frequency deviance paradigm. In addition, we measured the depressive mood using the Plutchik–van Praag (PVP) depression inventory.

Results

There was no significant between-group difference for the N1 latencies/amplitudes, both to the standard and deviant stimuli, and no significant between-group difference for MMN latencies. However, MMN amplitudes were higher in the TRD group than those in the other three groups. PVP scores were highest in TRD + BPD, then TRD, BPD patients, and lowest in healthy subjects. The higher MMN was not correlated with PVP score, nor with the duration of life-long depression, which can be considered as a neurophysiological marker for TRD.

Conclusion

An atypical lack of inhibition on the irrelevant stimuli or increased cortical neuronal activity, especially frontal area, or both, might be responsible for the finding.     

Facial expression of emotions in borderline personality disorder and depression

Borderline personality disorder (BPD) is characterized by marked problems in interpersonal relationships and emotion regulation. The assumption of emotional hyper-reactivity in BPD is tested regarding the facial expression of emotions, an aspect highly relevant for communication processes and a central feature of emotion regulation. Facial expressions of emotions are examined in a group of 30 female inpatients with BPD, 27 women with major depression and 30 non-patient female controls. Participants were videotaped while watching two short movie sequences, inducing either positive or negative emotions. Frequency of emotional facial expressions and intensity of happiness expressions were examined, using the Emotional Facial Action Coding System (EMFACS-7, Friesen & Ekman, EMFACS-7: Emotional Facial Action Coding System, Version 7. Unpublished manual, 1984). Group differences were analyzed for the negative and the positive mood-induction procedure separately. Results indicate that BPD patients reacted similar to depressed patients with reduced facial expressiveness to both films. The highest emotional facial activity to both films and most intense happiness expressions were displayed by the non-clinical control group. Current findings contradict the assumption of a general hyper-reactivity to emotional stimuli in patients with BPD.     

Anterior cingulate volume reduction in adolescents with borderline personality disorder and co-morbid major depression

Borderline Personality Disorder (BPD) is a serious illness characterized by emotional dysregulation, impulsivity, and impaired interpersonal relationships. Prior work shows the anterior cingulate gyrus (ACG)—a region primarily involved in assessing the salience of emotional information and regulating emotional responses--is smaller in adults with BPD. We tested the hypothesis that, similar to adults, adolescents with BPD would have reduced Brodmann area (BA)-24 volume. Thirteen adolescent inpatients with co-morbid BPD and Major Depressive Disorder (MDD) and 13 matched healthy controls received 3T-MRI scans. Using a cytoarchitecturally-derived approach measuring gray and white matter volume, we observed a Group × Cingulate BA (25,24,31,23,29) × Matter (gray, white) type interaction indicating the BPD/MDD adolescents had smaller BA24 volume in gray but not white matter. Greater number of suicide attempts and BPD symptom severity measured by the Diagnostic Interview for BPD-revised (DIB-R) total score but not depressive symptoms measured by the Beck Depression Inventory (BDI) was associated with smaller BA24 volume. Our preliminary findings suggest that BPD-related abnormalities in BA24 volume may occur early in the developmental course of BPD with MDD. Future studies examining samples of MDD patients with and without BPD co-morbidity will be needed to clarify whether BA24 volume reductions are specific to BPD.     

Training emotional intelligence improves both emotional intelligence and depressive symptoms in inpatients with borderline personality disorder and depression

Abstract

Objective. Borderline personality disorder (BPD) is defined as a pervasive pattern of instability in emotion, mood and interpersonal relationships, with a comorbidity between PBD and depressive disorders (DD). A key competence for successful management of interpersonal relationships is emotional intelligence (EI). Given the low EI of patients suffering from BPD, the present study aimed at investigating the effect on both emotional intelligence and depression of training emotional intelligence in patients with BPD and DD. Methods. A total of 30 inpatients with BPD and DD (53% females; mean age 24.20 years) took part in the study. Patients were randomly assigned either to the treatment or to the control group. Pre- and post-testing 4 weeks later involved experts’ rating of depressive disorder and self-reported EI. The treatment group received 12 sessions of training in components of emotional intelligence. Results. Relative to the control group, EI increased significantly in the treatment group over time. Depressive symptoms decreased significantly over time in both groups, though improvement was greater in the treatment than the control group. Conclusion. For inpatients suffering from BPD and DD, regular skill training in EI can be successfully implemented and leads to improvements both in EI and depression. Results suggest an additive effect of EI training on both EI and depressive symptoms.     

难治性抑郁症与首发未用药抑郁症患者认知功能比较

目的 探究难治性抑郁症患者与首发未用药抑郁症患者认知功能的差异,并分析抑郁症临床症状严重程度与认知功能的关系,为改善预后提供参考。方法 连续入组2016年11月-2019年12月在广州市某医院门诊就诊的首发未用药抑郁症患者119例、难治性抑郁症患者82例,并从社区招募71名健康人群作为健康对照组。采用汉密尔顿抑郁量表17项版（HAMD-17）及汉密尔顿焦虑量表（HAMA）评估被试的抑郁及焦虑症状,采用精神分裂症认知功能成套测验共识版（MCCB）评估认知功能,包括处理速度、工作记忆、语言学习与记忆、视觉学习与记忆。采用多元协方差分析比较三组认知功能的差异,采用偏相关分析分别探索两组患者组内HAMD-17、HAMA评分与MCCB四个维度评分的关系。结果 难治性抑郁症组和首发未用药抑郁症组MCCB的处理速度、视觉学习与记忆评分均低于健康对照组,难治性抑郁症组的工作记忆评分低于健康对照组,差异均有统计学意义（P<0.05或0.01）;难治性抑郁症组的处理速度、视觉学习与记忆评分均低于首发未用药抑郁症组,差异均有统计学意义（P<0.05或0.01）。偏相关分析结果显示,两组患者同组内HAMD-17、HAMA评分与MCCB四个认知功能维度评分均无相关性（P均>0.05）。结论 与首发未用药抑郁症患者和健康人群相比,难治性抑郁症患者的处理速度、视觉学习与记忆功能损伤更突出。而首发未用药抑郁症患者与难治性抑郁症患者,认知功能缺陷与抑郁、焦虑严重程度无相关性。     

Biological nature of depressive symptoms in borderline personality disorder: endocrine comparison to recurrent brief and major depression

Borderline personality disorder (BPD) often shows depressive symptoms and their biological nature albeit extensively discussed remains controversial. The knowledge of this nature seems essential as it could imply key therapeutic strategies. We have found BPD and major depression (MD) not to share biological abnormalities. We have proposed BPD to frequently display an affective syndrome distinct from the nonborderline MD both in terms of quality and duration of symptoms and of biological substrate. A substantial number of BPD patients can be diagnosed as having clinical Recurrent Brief Depression (RBD) which has been proposed to overlap with BPD. RBD has been found to share perturbed biological substrate with MD but we have previously not found this abnormal substrate in BPD. Our aim was to study the possibility that BPD patients with depressive symptoms and even clinically diagnosed with RBD have a biological substrate distinct from RBD without BPD and from MD, and therefore an specific affective syndrome. We compared 20 BPD in-patients without co-existing MD to 20 sex- and age-matched non-BPD recurrent brief depressives and to 20 sex- and age-matched non-BPD major depressives on the thyrotropin-releasing hormone stimulation test (TRH-ST) and the dexamethasone suppression test (DST). Twelve BPD patients were diagnosed as having also RBD. BPD had less TRH-ST blunting than MD. TRH-ST did not differentiate BPD from RBD. RBD and MD patients shared equivalent TRH-ST values but BPD patients with clinically diagnosed RBD did not. BPD and RBD showed less perturbed DST than MD. DST did not differentiate BPD from RBD. BPD and RBD share most of the endocrinological normal substrate already described in BPD but RBD also share abnormalities with MD. Whereas we can conceptualize RBD as being an endocrinologically perturbed depressive syndrome, this may not be the case for the possible specific affective syndrome of BPD even if it can be for now diagnosed as being RBD.     

Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls

Background

There is a decreased serotonergic function in impulsive aggression and borderline personality disorder (BPD), and genetic association studies suggest a role of serotonergic genes in impulsive aggression and BPD. Only one study has analyzed the association between the tryptophan-hydroxylase 2 (TPH2) gene and BPD. A TPH2 “risk” haplotype has been described that is associated with anxiety, depression and suicidal behavior.

Methods

We assessed the relationship between the previously identified “risk” haplotype at the TPH2 locus and BPD diagnosis, impulsive aggression, affective lability, and suicidal/parasuicidal behaviors, in a well-characterized clinical sample of 103 healthy controls (HCs) and 251 patients with personality disorders (109 with BPD). A logistic regression including measures of depression, affective lability and aggression scores in predicting “risk” haplotype was conducted.

Results

The prevalence of the “risk” haplotype was significantly higher in patients with BPD compared to HCs. Those with the “risk” haplotype have higher aggression and affect lability scores and more suicidal/parasuicidal behaviors than those without it. In the logistic regression model, affect lability was the only significant predictor and it correctly classified 83.1% of the subjects as “risk” or “non-risk” haplotype carriers.

Conclusions

We found an association between the previously described TPH2 “risk” haplotype and BPD diagnosis, affective lability, suicidal/parasuicidal behavior, and aggression scores.     

Emotional sensitivity,emotion regulation and impulsivity in borderline personality disorder: A critical review of fMRI studies

Emotional sensitivity, emotion regulation and impulsivity are fundamental topics in research of borderline personality disorder (BPD). Studies using fMRI examining the neural correlates concerning these topics is growing and has just begun understanding the underlying neural correlates in BPD. However, there are strong similarities but also important differences in results of different studies. It is therefore important to know in more detail what these differences are and how we should interpret these. In present review a critical light is shed on the fMRI studies examining emotional sensitivity, emotion regulation and impulsivity in BPD patients. First an outline of the methodology and the results of the studies will be given. Thereafter important issues that remained unanswered and topics to improve future research are discussed. Future research should take into account the limited power of previous studies and focus more on BPD specificity with regard to time course responses, different regulation strategies, manipulation of self-regulation, medication use, a wider range of stimuli, gender effects and the inclusion of a clinical control group.     

Yi-gan san for the treatment of borderline personality disorder: an open-label study

BACKGROUND: Numerous medications have been tested on patients with borderline personality disorder (BPD). Although many of these medications have been demonstrated to be useful, no clear main treatment for BPD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Chinese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in dementia patients. We aimed at evaluating both efficacy and safety of yi-gan san in patients with well-defined BPD. METHODS: Twenty female outpatients diagnosed with BPD according to DSM-IV criteria and the revised Diagnostic Interview for Borderlines completed a 12-week open-label study with yi-gan san at an average daily dosage of 6.4+/-1.9 g (2.5-7.5 g). Psychometric instruments to assess efficacy included the Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scales for Depression (HAM-D), Global Assessment of Functioning (GAF), Clinical Global Impression Scale (CGI), and Aggression Questionnaire (AQ). RESULTS: Most psychometric scale scores exhibited a highly significant improvement (total BPRS; BPRS somatic concern, anxiety, tension, depressive mood, hostility, suspiciousness, motor retardation, uncooperativeness, and excitement subscale; CGI; GAF; AQ) over time. CONCLUSIONS: In this open-label pilot study, patients treated with YGS showed statistically significant reduction on self-rated and clinician-rated scales. The present findings suggest that yi-gan san might be effective for the treatment of a number of BPD symptoms, including low mood, impulsivity, and aggression.     

Source imaging of P300 auditory evoked potentials and clinical correlations in patients with posttraumatic stress disorder

Objective

Posttraumatic stress disorder (PTSD) is associated with abnormal information processing. The P300 component of event-related potentials (ERPs) is known to be a useful marker of information processing. The purposes of this study were to determine the P300 current source density in PTSD patients, and its relationship with symptom severity.

Methods

ERPs were recorded in 30 PTSD patients and 33 healthy controls while participants were performing the auditory oddball task. We compared P300 current source density data - obtained by standardized low-resolution brain electromagnetic tomography (sLORETA) - between the two groups. The correlation between P300 current source density and clinical symptoms (as evaluated using the Korean version of the Structured Interview for PTSD — K-SIPS and Davidson Trauma Scale — K-DTS) was conducted.

Results

In PTSD patients, the current source density of P300 is significantly reduced in the inferior frontal gyrus, precentral gyrus, insula, and anterior cingulate compared to healthy controls. Total K-DTS scores were correlated with the P300 current source density in the posterior cingulate gyrus. The K-SIP B items (re-experiencing) and K-SIB D items (increased arousal) were positively correlated with P300 current source densities in several brain regions located in the frontal, parietal, and temporal lobe (p < 0.05). Conversely, the K-SIP C items (avoidance and numbing) were negatively correlated with P300 current source densities in the superior and middle frontal gyri in the frontal lobes (p < 0.05).

Conclusion

The P300 current source densities reflected the pathophysiology of PTSD patients. PTSD symptoms were related to different neural activities, depending on their symptom characteristics.     

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: A resting-state fMRI study

Background

Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients.

Methods

Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans.

Results

There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit.

Conclusions

The affected brain circuits of TRD patients might be partly different from those of TSD patients.