Neural correlates of emotion acceptance and suppression in borderline personality disorder.

Background: Emotion dysregulation is a central feature of borderline personality disorder (BPD). Since impaired emotion regulation contributes to disturbed emotion functioning in BPD, it is crucial to study underlying neural activity. The current study aimed at investigating the neural correlates of two emotion regulation strategies, namely emotion acceptance and suppression, which are both important treatment targets in BPD. Methods: Twenty-one women with BPD and 23 female healthy control participants performed an emotion regulation task during functional magnetic resonance imaging (fMRI). While watching fearful movie clips, participants were instructed to either accept or to suppress upcoming emotions compared to passive viewing. Results: Results revealed acceptance-related insular underactivation and suppression-related caudate overactivation in subjects with BPD during the emotion regulation task. Conclusion: This is a first study on the neural correlates of emotion acceptance and suppression in BPD. Altered insula functioning during emotion acceptance may reflect impairments in emotional awareness in BPD. Increased caudate activity is linked to habitual motor and cognitive processes and therefore may accord to the well-established routine in BPD patients to suppress emotional experiences.

Caudate hyperactivation during the processing of happy faces in borderline personality disorder.

BACKGROUND: Emotion dysfunction and anhedonia are main problems in borderline personality disorder (BPD). In the present functional magnetic resonance imaging (fMRI) study, we investigated neural activation during the processing of happy faces and its correlates with habitual emotion acceptance in patients with BPD. METHODS: 22 women with BPD and 26 female healthy controls watched movie clips of happy and neutral faces during fMRI without any instruction of emotion regulation. To associate neural activation with habitual emotion acceptance, we included individual scores of the Emotion Acceptance Questionnaire (EAQ) as a covariate in brain data analysis. RESULTS: All participants showed amygdala, temporal and occipital activation during the processing of happy compared to neutral faces. Compared with healthy controls, patients with BPD showed significantly more activation within the bilateral caudate. We did not find significant correlations with emotion acceptance. CONCLUSIONS: Our results indicate caudate hyperactivation in patients with BPD during the processing of happy faces. Although patients reported significantly less emotion acceptance of positive emotions, an association with neural activation was not detectable.

Nonacceptance of negative emotions in women with borderline personality disorder: association with neuroactivity of the dorsal striatum

Background: Emotion dysfunction is a key symptom in patients with borderline personality disorder (BPD) and is considered a consequence of dysfunctional emotion regulation (e.g., reduced emotion acceptance). In the present functional MRI (fMRI) study, we investigated the neural correlates of habitual emotion acceptance in individuals with BPD. Methods: Female patients with BPD and female healthy controls passively viewed negative and neutral movie clips of faces during fMRI. We assessed emotion acceptance using the Emotion Acceptance Questionnaire (EAQ). To examine brain activation associated with habitual emotional acceptance of negative stimuli, the EAQ score was included as a regressor of interest in brain data analyses of activation intensity during negative compared with neutral movies. Results: We included 20 women with BPD and 20 heatlhy controls in our analysis. Compared with healthy controls, patients with BPD showed significantly more activation in frontostriatal brain regions (i.e., left superior frontal gyrus, right caudate) as well as in the left precuneus, left precentral gyrus, left posterior cingulate cortex and left hippocampus when confronted with negative (v. neutral) stimuli. Patients with BPD reported decreased emotion acceptance compared with healthy controls, and habitual emotion acceptance was inversely associated with activation of striatal areas (i.e., left putamen, left caudate) in patients with BPD. Limitations: Causal conclusions are not possible. Comorbid diagnoses were not excluded, and only female participants were investigated. Stimuli were not rated immediately and may not be generalizable to all negative emotions. We cannot make any statements about other emotion-regulation strategies that may have been applied here. Conclusion: Data indicate that striatal hyperactivation during the processing of negative stimuli in women with BPD is related to their decreased disposition to accept unpleasant emotional states. Thus, individuals with BPD may benefit from therapy approaches that focus on emotion acceptance in order to normalize emotional reactions.

Effects of cortisol on the memory bias for emotional words? A study in patients with depression and healthy participants using the Directed Forgetting task.

Mood congruent alterations in information processing such as an impaired memory bias for emotional information and impaired inhibitory functions are prominent features of a major depressive disorder (MDD). Furthermore, in MDD patients hypothalamic-pituitary-adrenal axis dysfunctions are frequently found. Impairing effects of stress or cortisol administration on memory retrieval as well as impairing stress effects on cognitive inhibition are well documented in healthy participants. In MDD patients, no effect of acute cortisol administration on memory retrieval was found. The current study investigated the effect of acute cortisol administration on memory bias in MDD patients (N = 55) and healthy controls (N = 63) using the Directed Forgetting (DF) task with positive, negative and neutral words in a placebo controlled, double blind design. After oral administration of 10 mg hydrocortisone/placebo, the item method of the DF task was conducted. Memory performance was tested with a free recall test. Cortisol was not found to have an effect on the results of the DF task. Interestingly, there was significant impact of valence: both groups showed the highest DF score for positive words and remembered significantly more positive words that were supposed to be remembered and significantly more negative words that were supposed to be forgotten. In general, healthy participants remembered more words than the depressed patients. Still, the depressed patients were able to inhibit intentionally irrelevant information at a comparable level as the healthy controls. These results demonstrate the importance to distinguish in experimental designs between different cognitive domains such as inhibition and memory in our study.

Minimization of Childhood Maltreatment Is Common and Consequential: Results from a Large, Multinational Sample Using the Childhood Trauma Questionnaire.

Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale-originally designed to assess a positive response bias-are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ's MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ's discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores attenuate the ability of the CTQ to distinguish between psychiatric patients and community volunteers. Overall, results suggest that a minimizing response bias-as detected by the MD subscale-has a small but significant moderating effect on the CTQ's discriminative validity. Results also may suggest that some prior analyses of maltreatment rates or the effects of early maltreatment that have used the CTQ may have underestimated its incidence and impact. We caution researchers and clinicians about the widespread practice of using the CTQ without the MD or collecting MD data but failing to assess and control for its effects on outcomes or dependent variables.

Subjective memory complaints and memory performance in patients with borderline personality disorder.

BACKGROUND: It is still a matter of debate as to whether patients with Borderline Personality Disorder (BPD) suffer from memory deficits. Existing studies indicate no or small impairments in memory test performance. However, it was shown in patients with related disorders, such as depression, that self-reported impairment exceeds test malfunction. In the present study we assessed memory performance of BPD patients through the use of memory tests and a questionnaire for subjective memory complaints (SMC) in everyday life. METHODS: Thirty-two patients with BPD and 32 healthy control subjects were included in the study. The groups of subjects were comparable with respect to age, education, and gender. Subjects completed verbal and nonverbal memory tests, as well as the everyday memory questionnaire (EMQ). RESULTS: BPD patients reported severe SMC but did not show memory test impairment. The results remained stable even when all BPD patients with acute or lifetime depression comorbidity were excluded from analyses. In both groups, SMC and test performances were not related but in BPD patients SMC were related to BPD symptoms. CONCLUSIONS: Our data indicate memory impairment of BPD patients in everyday life. However, it cannot be ruled out that increased memory complaints result from patients' negative self-perception. Future research needs to clarify the reasons for memory complaints of BPD patients.

The impact of self-reported childhood trauma on emotion regulation in borderline personality disorder and major depression.

Early life stress is said to play a critical role in the development of borderline personality disorder (BPD) and major depressive disorder (MDD), but the underlying mediating factors remain uncertain. This study aimed to investigate self-reported childhood trauma, emotion regulation difficulties, and their associations in a sample of BPD (n = 49) and MDD (n = 48) patients and healthy control participants (n = 63). Multiple regressions were used to evaluate the impact of the quality and severity of self-reported childhood trauma on self-reported emotion regulation. The results supported an association between self-reported maltreatment experiences, especially emotional abuse and neglect, and emotion regulation difficulties. Additional analyses showed that emotion regulation difficulties influence the association between self-reported emotional abuse and acute symptomatology in the BPD subgroup. Emotion regulation difficulties may be 1 pathway through which early life stress, particularly emotional abuse, increases the risk for developing BPD symptomatology.

Acute glucocorticoid effects on response inhibition in borderline personality disorder.

INTRODUCTION: Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. METHODS: After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. RESULTS: Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. CONCLUSIONS: Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters.

Increased attempts to suppress negative and positive emotions in Borderline Personality Disorder.

Patients with Borderline Personality Disorder (BPD) show evidence of disturbed emotion regulation. In particular, patients may try to suppress their emotions with possibly negative effects on mental health. We investigated the suppression of both negative and positive emotions in BPD patients and healthy participants. Thirty BPD patients and 30 matched healthy controls were assessed for emotion suppression using the Emotion Acceptance Questionnaire (EAQ). In addition, we administered additional questionnaires to validate emotion suppression findings. BPD patients reported increased attempts to suppress both negative and positive emotions. These findings indicate that BPD patients are not simply acting out negative emotions. Therapeutic approaches that focus on emotion acceptance of emotions are supported by our study data. Apart from negative emotions, treatment programs should consider positive emotions as well.

Cortisol effects on autobiographic memory retrieval in PTSD: an analysis of word valence and time until retrieval.

In healthy participants, cortisol administration has been found to impair autobiographic memory retrieval. We recently reported that administration of 10 mg of hydrocortisone had enhancing effects on autobiographical memory retrieval, i.e. more specific memory retrieval, in patients with posttraumatic stress disorder (PTSD), while in healthy controls the impairing effects were replicated. We here report a re-analysis of these data with respect to cue-word valence and retrieval time. In a placebo-controlled cross-over study, 43 patients with PTSD and 43 age- and sex-matched healthy controls received either placebo or hydrocortisone orally before the autobiographical memory test was performed. We found that the effects of cortisol on memory retrieval depended on cue-word valence and group (significant interaction effects of drug by group and drug by valence by group). The enhancing effect of cortisol on memory retrieval in PTSD seemed to be relatively independent of cue-word valence, while in the control group the impairing effects of cortisol were only seen in response to neutral cue-words. The second result of the study was that in patients as well as in controls, cortisol administration led to faster memory retrieval compared to placebo. This was seen in response to positive and (to lesser extend) to neutral cue-words, but not in response to negative cue-words. Our findings illustrate that the opposing effects of cortisol on autobiographical memory retrieval in PTSD patients and controls are further modulated by the emotionality of the cue-words.

Effects of acute cortisol administration on response inhibition in patients with major depression and healthy controls.

Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition.

Associations of childhood trauma with hypothalamic-pituitary-adrenal function in borderline personality disorder and major depression.

BACKGROUND: Alterations of the hypothalamus-pituitary-adrenal (HPA) axis are hallmarks in major depressive disorder (MDD) and there is some evidence about similar patterns in borderline personality disorder (BPD). This study examines HPA axis abnormalities with respect to clinical characteristics in both BPD (n=24) and MDD patients (n=33) as well as in healthy control participants (n=41). METHOD: A 0.5mg dexamethasone suppression test was administered to evaluate basal cortisol release and HPA feedback sensitivity via salivary cortisol. Traumatic experiences in childhood as well as severity of borderline and depressive symptom severity and dissociation were obtained by self-report questionnaires. RESULTS: Compared to the healthy control group, BPD and MDD patients exhibited both enhanced cortisol concentrations before and after the administration of 0.5mg dexamethasone. Higher cortisol levels were positively correlated to a history of childhood trauma, current dissociative symptoms and severity of borderline and depressive symptoms. Regression analyses revealed that some aspects of early trauma were associated with cortisol release before and after dexamethasone, whereas psychopathology did not contribute to the regression model. CONCLUSIONS: HPA dysfunctions appear to be related rather to childhood trauma than to psychopathology in adulthood. Exposure to childhood trauma may contribute to long-lasting alterations in HPA activity and might enhance the risk for the development of later mental disorder.

Cortisol has enhancing, rather than impairing effects on memory retrieval in PTSD.

BACKGROUND: In the present study, we aimed to compare the effect of exogenous cortisol on memory retrieval in posttraumatic stress disorder (PTSD) with the effects in healthy controls. In healthy participants, administration of cortisol impairs declarative memory retrieval. Only a few studies have investigated these effects in PTSD yielding mixed results. METHODS: In a placebo-controlled crossover study, 44 patients with PTSD and 65 healthy controls received either placebo or 10mg of hydrocortisone orally before memory testing. In addition to declarative memory retrieval (word list learning), we also tested autobiographical memory retrieval specificity. RESULTS: In both tasks opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval, while in PTSD patients cortisol had enhancing effects on memory retrieval in both memory domains. CONCLUSIONS: The present results suggest beneficial effects of acute cortisol elevations on hippocampal mediated memory processes in PTSD. Possible neurobiological mechanisms underlying these findings are discussed.

Selective attention in depression: influence of emotionality and personal relevance.

Selective attention to negative stimuli has been discussed as being an essential characteristic of depressive disorder. Theories and empirical data, however, are contradictory. The present study addressed the question of whether depressive patients selectively attend to negatively valenced and personally relevant or irrelevant stimuli and whether they habituate to these stimuli. Thirty-one inpatients with major depressive disorder and 37 healthy controls participated in the study. They underwent a modification of the emotional Stroop paradigm. The results indicated that personally relevant stimuli evoked more pronounced Stroop interference than did stimuli without personal relevance in all subjects. Furthermore, habituation to personally relevant negative stimuli was seen in both depressive patients and control subjects. The present findings question a generally negative attentional bias as being a specific characteristic of depressive disorder. Furthermore, as depressed patients habituated to personally relevant negative stimuli, exposure therapy might be suitable for the treatment of depressive disorder.

Patients with borderline personality disorder and major depressive disorder are not distinguishable by their neuropsychological performance: a case-control study.

OBJECTIVE: Patients with borderline personality disorder (BPD) and patients with major depressive disorder (MDD) exhibit a broad range of neuropsychological deficits. Studies in both groups of patients point to differences but also similarities. However, studies that compare both patient groups are missing from the literature. The present study aimed to compare neuropsychological functioning in BPD and MDD patients. METHOD: Eighteen patients with BPD, 27 patients with MDD, 17 patients with BPD and MDD, and 76 healthy control subjects were included in the case-control study. Patients were treated for their disorders as inpatients of the Clinic of Psychiatry and Psychotherapy Bethel, Ev. Hospital Bielefeld (Bielefeld, Germany). All patients met DSM-IV diagnoses as assessed by trained psychotherapists within the first week of their admission. In addition to a comprehensive neuropsychological test battery, the inhibitory control of emotional stimuli was assessed. Data were collected between June 2004 and June 2007. RESULTS: Patients showed only a few impairments and no increased distractibility toward emotionally negative stimuli. Patients with BPD and patients with MDD were not distinguishable by the neuropsychological test results. CONCLUSIONS: These data did not support the notion of specific neuropsychological profiles in BPD and MDD. Future research needs to clarify the overlap of symptoms between both disorders.

Effects of acute hydrocortisone administration on declarative memory in patients with major depressive disorder: a placebo-controlled, double-blind crossover study.

OBJECTIVE: Major depressive disorder (MDD) has been associated with hypercortisolism, reduced glucocorticoid feedback sensitivity, and impaired memory function. In healthy subjects, administration of hydrocortisone impairs declarative memory. The aim of this study was to examine the effects of acute hydrocortisone administration on memory retrieval in MDD patients and healthy controls. We further tested whether the enhancing or impairing effects of hydrocortisone would prevail when it was given after encoding and when delayed retrieval was tested at a time point when glucocorticoid levels were still elevated. METHOD: In a placebo-controlled, double-blind crossover study, 44 patients with DSM-IV MDD and 51 healthy control participants received either placebo or 10 mg of hydrocortisone orally before memory testing. A word list paradigm and the Logical Memory Test from the Wechsler Memory Scale were applied. The study was conducted from April 2008 until April 2010 at sites in Bielefeld and Hamburg, Germany. RESULTS: In both memory tests, patients with MDD performed worse than controls. Healthy controls showed impaired memory performance after hydrocortisone administration compared to placebo. In contrast, hydrocortisone had no effects on memory in MDD patients. Furthermore, in healthy controls we found that administration of hydrocortisone immediately after learning did not lead to an enhanced free recall during increased cortisol levels. CONCLUSIONS: It appears that the impairing effects of hydrocortisone on memory performance are missing in patients with MDD. This might be interpreted in the context of reduced central glucocorticoid receptor functioning.

Hydrocortisone impairs working memory in healthy humans, but not in patients with major depressive disorder.

OBJECTIVE: Several studies have shown that stress or the administration of glucocorticoids can impair hippocampus-based declarative memory retrieval and prefrontal dependent working memory performance in healthy subjects. Major Depressive Disorder (MDD) is often characterized by memory impairment and increased cortisol secretion. Studies indicate that the impairing effects of glucocorticoids on declarative memory performance are missing in patients with MDD. The purpose of our study was to investigate whether the finding of missing effects of acute cortisol administration on memory performance in MDD is also seen when examining prefrontal-based working memory. METHODS: In a placebo-controlled study, 57 patients with MDD and 56 sex- and age-matched healthy control subjects received either placebo or 10 mg of hydrocortisone orally before memory testing. To test the verbal modality of working memory, the Word Suppression Test was applied with one negative and one neutral test part. RESULTS: After hydrocortisone intake, healthy subjects showed a significantly poorer working memory performance compared to placebo treatment when negative interference words were administered. In contrast, memory performance of MDD patients was not affected by hydrocortisone treatment. CONCLUSIONS: The missing effects of glucocorticoid administration on working memory in MDD might be interpreted in the context of reduced central glucocorticoid receptor function.

Cognitive correlates of hypothalamic-pituitary-adrenal axis in major depression.

Depressive disorder has become a major health problem and is ranked among the leading causes of disability worldwide. Depression-related cognitive impairment contributes to loss of economic productivity and psychosocial functioning and calls for more efficient treatment strategies. Although the pathogenesis of cognitive impairments in patients with major depressive disorder (MDD) is still insufficiently understood, increasing evidence implicates hypothalamus-pituitary-adrenal (HPA) axis as an important neurobiological determinant of cognitive impairment in depression. In this article, major findings of both HPA axis function abnormalities and cognitive impairments in depressed patients are summarized, focusing on their inter-relationship. Novel approaches in pharmacotherapy and psychotherapy have emerged which will be discussed with regard to their ability to reinstate normal HPA axis function in MDD and to treat cognitive impairments in MDD.

The impact of neutral and emotionally negative distraction on memory performance and its relation to memory complaints in major depression.

Patients with major depression (MDD) often report relevant cognitive problems in everyday life while performance in standardised neuropsychological tests is not severely disturbed. This discrepancy may partly be due to the differences between the demands of everyday life with the presence of emotionally relevant distractors and standardised neuropsychological settings without those distractors. In the present study, we hypothesise that patients with major depression (MDD) show an increased distractibility towards emotionally negative stimuli and that this distractibility is related to complaints of cognitive functioning in everyday life. Thirty MDD patients and 48 healthy participants performed our recently developed learning paradigm with neutrally and negatively valenced distraction as well as without distraction. Both groups also performed a neuropsychological test battery as well as self- and observer ratings of impairments in memory and attention in every day life. In the MDD sample, cognitive impairments were reported by the patients and their relatives but were not found in the neuropsychological tests. We found a trend towards a poorer memory performance with negatively valenced distraction in the MDD sample when compared to the performance of healthy subjects. However, this impairment was not related to the self- and observer ratings. This result may be due to the fact that the distractors were not personally relevant to the subjects whereas everyday life implies such distractors. Further research is needed to explore everyday cognitive functioning of patients with MDD.