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1.  Negative Evaluation Bias for Positive Self-Referential Information in Borderline Personality Disorder 
PLoS ONE  2015;10(1):e0117083.
Previous research has suggested that patients meeting criteria for borderline personality disorder (BPD) display altered self-related information processing. However, experimental studies on dysfunctional self-referential information processing in BPD are rare. In this study, BPD patients (N = 30) and healthy control participants (N = 30) judged positive, neutral, and negative words in terms of emotional valence. Referential processing was manipulated by a preceding self-referential pronoun, an other-referential pronoun, or no referential context. Subsequently, patients and participants completed a free recall and recognition task. BPD patients judged positive and neutral words as more negative than healthy control participants when the words had self-reference or no reference. In BPD patients, these biases were significantly correlated with self-reported attributional style, particularly for negative events, but unrelated to measures of depressive mood. However, BPD patients did not differ from healthy control participants in a subsequent free recall task and a recognition task. Our findings point to a negative evaluation bias for positive, self-referential information in BPD. This bias did not affect the storage of information in memory, but may be related to self-attributions of negative events in everyday life in BPD.
PMCID: PMC4303263  PMID: 25612212
2.  Trauma-related altered states of consciousness in women with BPD with or without co-occurring PTSD 
European Journal of Psychotraumatology  2014;5:10.3402/ejpt.v5.24863.
A “4-D model” was recently described as a theoretical framework for categorizing trauma-related symptoms into four phenomenological dimensions (the experience of time, thought, body, and emotion) that can present either in the form of normal waking consciousness (NWC) or as dissociative experiences, that is, trauma-related altered states of consciousness (TRASC).
The present study examined the predictions of the 4-D model in 258 persons with borderline personality disorder (BPD) with (n=126) versus without (n=132) posttraumatic stress disorder (PTSD).
As measured by the Borderline Symptom List, consistent with the predictions of the 4-D model, in comparison with symptom endorsements theorized to be associated with NWC, measures of TRASC were less frequent, and more strongly correlated with both Dissociative Experience Scale scores and severity of childhood emotional neglect, particularly in persons with both BPD and PTSD. Our prediction that symptoms of TRASC would be less intercorrelated in comparison with distress associated with NWC symptoms, however, was not supported.
Findings are discussed as they pertain to the symptomatology of BPD, PTSD, and dissociation.
PMCID: PMC4138496  PMID: 25206942
Dissociation; borderline personality disorder; posttraumatic stress disorder; trauma-related altered states of consciousness; childhood abuse and neglect; 4-D model
3.  Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder 
Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.
PMCID: PMC4153044  PMID: 25232313
impulsivity; response inhibition; borderline personality disorder; attention-deficit/hyperactivity disorder, fMRI
4.  Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample 
Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g., for subjects suffering from emotion dysregulation. As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N = 16) and a control group was presented with feedback from a control region located in the basal ganglia [N(sum) = 32]. Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning. In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole-brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed. We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of NF training for amygdala regulation.
PMCID: PMC4166899  PMID: 25278851
affective disorders; amygdala; emotion regulation; mPFC; emotions; real-time fMRI neurofeedback; affective symptoms; instrumental learning
5.  Amygdala and Dorsal Anterior Cingulate Connectivity during an Emotional Working Memory Task in Borderline Personality Disorder Patients with Interpersonal Trauma History 
Working memory is critically involved in ignoring emotional distraction while maintaining goal-directed behavior. Antagonistic interactions between brain regions implicated in emotion processing, e.g., amygdala, and brain regions involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal cortex (dlPFC, dmPFC), may play an important role in coping with emotional distraction. We previously reported prolonged reaction times associated with amygdala hyperreactivity during emotional distraction in interpersonally traumatized borderline personality disorder (BPD) patients compared to healthy controls (HC): Participants performed a working memory task, while neutral versus negative distractors (interpersonal scenes from the International Affective Picture System) were presented. Here, we re-analyzed data from this study using psychophysiological interaction analysis. The bilateral amygdala and bilateral dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest. Whole-brain regression analyses with reaction times and self-reported increase of dissociation were performed. During emotional distraction, reduced amygdala connectivity with clusters in the left dorsolateral and ventrolateral PFC was observed in the whole group. Compared to HC, BPD patients showed a stronger coupling of both seeds with a cluster in the right dmPFC and stronger positive amygdala connectivity with bilateral (para)hippocampus. Patients further demonstrated stronger positive dACC connectivity with left posterior cingulate, insula, and frontoparietal regions during emotional distraction. Reaction times positively predicted amygdala connectivity with right dmPFC and (para)hippocampus, while dissociation positively predicted amygdala connectivity with right ACC during emotional distraction in patients. Our findings suggest increased attention to task-irrelevant (emotional) social information during a working memory task in interpersonally traumatized patients with BPD.
PMCID: PMC4211399  PMID: 25389397
amygdala; anterior cingulate cortex; borderline personality disorder; emotional distraction; emotional working memory; functional connectivity; interpersonal trauma; psychophysiological interactions
6.  Gene Expression Profiles in Relation to Tension and Dissociation in Borderline Personality Disorder 
PLoS ONE  2013;8(8):e70787.
The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression. We conducted a whole blood gene expression profile analysis using quantitative PCR in 31 female inpatients with BPD. For each individual, two samples were drawn during a state of high tension and dissociation, while two samples were drawn at non-tension states. There was no association between gene expression and tension states. However, we could show that Interleukin-6 was positively correlated to dissociation scores, whereas Guanine nucleotide-binding protein G(s) subunit alpha isoforms, Mitogen-activated protein kinase 3 and 8, Guanine nucleotide-binding protein G(i) subunit alpha-2, Beta-arrestin-1 and 2, and Cyclic AMP-responsive element-binding protein were negatively correlated to dissociation. Our data point to a potential association of dissociation levels with the expression of genes involved in immune system regulation as well as cellular signalling/second-messenger systems. Major limitations of the study are the the possibly heterogeneous cell proportions in whole blood and the heterogeneous medication.
PMCID: PMC3741306  PMID: 23951008
7.  Voxel-Based Morphometry in Women with Borderline Personality Disorder with and without Comorbid Posttraumatic Stress Disorder 
PLoS ONE  2013;8(6):e65824.
Patients with Borderline Personality Disorder (BPD) showed reduced volume of amygdala and hippocampus, but similar findings are evident in Posttraumatic Stress Disorder (PTSD). Applying voxel-based morphometry (VBM) in a larger cohort of patients with BPD, we sought to extend earlier findings of volume abnormalities in limbic regions and to evaluate the influence of co-occurring PTSD in BPD patients. We used voxel-based morphometry to study gray matter volume (GMV) in 60 healthy controls (HC) and 60 patients with BPD. Subgroup analyses on 53 patients concerning the role of co-occurring PTSD were conducted. Additionally, regression analyses were calculated to assess the relation between borderline symptom severity as well as dissociative experiences and GMV. Differences in local GMV between patients with BPD and HC were observed in the amygdale and hippocampus as well as in the fusiform and cingulate gyrus. Co-occurring PTSD was accompanied by increased GMV in the superior temporal gyrus and dorsolateral prefrontal cortex. Independent of co-occurring PTSD, severity of BPD symptoms predicted smaller GMV in the amygdala and dorsal ACC. Dissociation was positively related to GMV in the middle temporal gyrus. We could replicate earlier findings of diminished limbic GMV in patients with BPD and additionally show that patients with co-morbid PTSD feature increased GMV in prefrontal regions associated with cognitive control.
PMCID: PMC3680473  PMID: 23776553
8.  Functional Connectivity of Pain-Mediated Affect Regulation in Borderline Personality Disorder 
PLoS ONE  2012;7(3):e33293.
Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.
We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception).
Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate).
We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.
PMCID: PMC3299768  PMID: 22428013
9.  COMT val158met Polymorphism and Neural Pain Processing 
PLoS ONE  2012;7(1):e23658.
A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant – though moderate - effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing.
PMCID: PMC3256133  PMID: 22247753
10.  A Positron Tomographic Emission Study of Olfactory Induced Emotional Recall in Veterans with and without Combat-related Posttraumatic Stress Disorder 
Psychopharmacology bulletin  2007;40(1):8-30.
Memory for odors is often associated with highly emotional experiences, and odors have long been noted by clinicians to be precipitants of trauma symptoms in PTSD. Primitive brain systems involved in fear responsivity and survival also mediate smell, including the olfactory cortex and amygdala. The purpose of this study was to measure neural correlates of olfaction in PTSD.
We exposed male combat veterans with PTSD (N=8) and without PTSD (N=8) to a set of smells, including diesel (related to traumatic memories of combat), and three other types of smells: odorless air, vanilla/coconut and hydrogen sulfide (H2S) (resp. a neutral, positive, and negative hedonic non-traumatic smell) in conjunction with PET imaging of cerebral blood flow and assessment of psychophysiological and behavioral symptoms. All subjects also underwent a baseline of olfactory acuity.
PTSD patients rated diesel as unpleasant and distressing, resulting in increased PTSD symptoms and anxiety in PTSD versus combat controls. Exposure to diesel resulted in an increase in regional blood flow (rCBF) in amygdala, insula, medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), and decreased rCBF in lateral prefrontal cortex (lPFC) in PTSD in comparison to combat controls. Combat controls showed less rCBF changes on any smell, and did not show amygdala activation upon diesel exposure.
These data support the hypothesis that in PTSD trauma-related smells can serve as strong emotional reminders. The findings indicate the involvement of a neural circuitry that shares olfactory elements and memory processing regions when exposed to trauma-related stimuli.
PMCID: PMC3236699  PMID: 17285093
PTSD; brain imaging techniques; olfaction; memory; amygdala
11.  Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder 
The American journal of psychiatry  2006;163(4):630-636.
Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma.
The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared.
Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups.
The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.
PMCID: PMC3233754  PMID: 16585437
12.  Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder 
Psychological medicine  2005;35(6):791-806.
In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD).
Women with early childhood sexual-abuse-related PTSD (n=8) and women without abuse or PTSD (n=11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square.
Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls.
These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.
PMCID: PMC3233760  PMID: 15997600
13.  Neuroimaging in borderline personality disorder 
Journal of psychiatric research  2005;40(5):419-427.
Neuroimaging has become one of the most important methods in the investigation of the neurobiological underpinnings of borderline personality disorder. Structural and functional imaging studies have revealed dysfunction in different brain regions which seem to contribute to borderline symptomatology. This review presents relevant studies using different methodologies: volumetry of limbic and prefrontal regions, investigations of brain metabolism under resting conditions, studies of serotonergic neurotransmission, and challenge studies using emotional, stressful, and sensory stimuli. Dysfunction in a frontolimbic network is suggested to mediate much, if not all of the borderline symptomatology.
PMCID: PMC3233768  PMID: 16239012
Neuroimaging; Borderline personality disorder; Prefrontal cortex; Amygdala
14.  Alterations in Stress Reactivity After Long-Term Treatment with Paroxetine in Women with Posttraumatic Stress Disorder 
Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress.
PMCID: PMC3230329  PMID: 16891570
cortisol; PTSD; stress; paroxetine; SSRI; challenge; HPA axis
15.  Emotion Modulation in PTSD: Clinical and Neurobiological Evidence for a Dissociative Subtype 
The American journal of psychiatry  2010;167(6):640-647.
In this article, the authors present evidence regarding a dissociative subtype of PTSD, with clinical and neurobiological features that can be distinguished from nondissociative PTSD. The dissociative subtype is characterized by overmodulation of affect, while the more common undermodulated type involves the predominance of reexperiencing and hyperarousal symptoms. This article focuses on the neural manifestations of the dissociative subtype in PTSD and compares it to those underlying the reexperiencing/hyperaroused subtype. A model that includes these two types of emotion dysregulation in PTSD is described. In this model, reexperiencing/hyperarousal reactivity is viewed as a form of emotion dysregulation that involves emotional undermodulation, mediated by failure of prefrontal inhibition of limbic regions. In contrast, the dissociative subtype of PTSD is described as a form of emotion dysregulation that involves emotional overmodulation mediated by midline prefrontal inhibition of the same limbic regions. Both types of modulation are involved in a dynamic interplay and lead to alternating symptom profiles in PTSD. These findings have important implications for treatment of PTSD, including the need to assess patients with PTSD for dissociative symptoms and to incorporate the treatment of dissociative symptoms into stage-oriented trauma treatment.
PMCID: PMC3226703  PMID: 20360318
16.  Structural and functional plasticity of the human brain in posttraumatic stress disorder 
Progress in brain research  2008;167:171-186.
Posttraumatic stress disorder (PTSD) is associated with long-term changes in neurobiology. Brain areas involved in the stress response include the medial prefrontal cortex, hippocampus, and amygdala. Neurohormonal systems that act on the brain areas to modulate PTSD symptoms and memory include glucocorticoids and norepinephrine. Dysfunction of these brain areas is responsible for the symptoms of PTSD. Brain imaging studies show that PTSD patients have increased amygdala reactivity during fear acquisition. Other studies show smaller hippocampal volume. A failure of medial prefrontal/anterior cingulate activation with re-experiencing of the trauma is hypothesized to represent a neural correlate of the failure of extinction seen in PTSD. The brain has the capacity for plasticity in the aftermath of traumatic stress. Antidepressant treatments and changes in environment can reverse the effects of stress on hippocampal neurogenesis, and humans with PTSD showed increased hippocampal volume with both paroxetine and phenytoin.
PMCID: PMC3226705  PMID: 18037014
PET; depression; cortisol; glucocorticoids; stress; PTSD
17.  Pain sensitivity and neural processing during dissociative states in patients with borderline personality disorder with and without comorbid posttraumatic stress disorder: a pilot study 
Stress-induced dissociative states involving analgesia are a common feature of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD). Our aim was to investigate the psychologic, somatosensory (pain sensitivity) and neural correlates of dissociative states in patients with these disorders.
We included 15 women with BPD who were not taking medication; 10 of these women had comorbid PTSD. While undergoing functional magnetic resonance imaging at 1.5 Tesla, participants were exposed to a script describing a personalized dissociation-inducing situation and a personalized script describing a neutral situation. We assessed dissociative psychopathology and pain sensitivity.
Dissociative psychopathology scores were significantly higher and pain sensitivity was lower after the dissociation-inducing script was read compared with the neutral script. The blood oxygen level–dependent (BOLD) signal was significantly increased in the left inferior frontal gyrus (Brodmann area [BA] 9) during the presentation of the dissociation-inducing script. Regression analyses revealed positive correlations between BOLD signal and dissociative psychopathology in the left superior frontal gyrus (BA 6) and negative correlations in the right middle (BA 21) and inferior temporal gyrus (BA 20). In the subgroup of participants with comorbid PTSD, we also found increased activity in the left cingulate gyrus (BA 32) during script-driven imagery-induced dissociation, a positive correlation between dissociation scores and activity in the right and left insula (BA 13) and a negative correlation in the right parahippocampal gyrus (BA 35).
The main limitation of this pilot study is the absence of a control group. Therefore, the results may also reflect the neural correlates of non–BPD/PTSD specific dissociative states or the neural correlates of emotionally stressful or “loaded” memories. Another limitation is the uncorrected statistical level of the functional magnetic resonance imaging results.
Our results showed that the script-driven imagery method is capable of inducing dissociative states in participants with BPD with and without comorbid PTSD. These states were characterized by reduced pain sensitivity and a frontolimbic activation pattern, which resembles the findings in participants with PTSD while in dissociative states.
PMCID: PMC2861134  PMID: 20420768
18.  Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder 
Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD.
We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1- and T2-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala.
Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD.
Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size.
Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.
PMCID: PMC2702446  PMID: 19568480
19.  Emotional learning during dissociative states in borderline personality disorder 
Neurobiological findings and clinical data suggest that dissociative experience inhibits conditioning processes, but experimental studies are lacking. The aim of our study was to determine whether high states of dissociative experience would specifically alter emotional learning, but not declarative knowledge.
We used an aversive differential delay conditioning procedure in 33 unmedicated patients with borderline personality disorder (BPD) and 35 healthy controls.
Patients with BPD who had high state dissociative experiences (BPD D+) showed diminished acquisition of differential aversive delay conditioning with respect to emotional learning compared with those who did not experience dissociative symptoms (BPD D−) and healthy controls (skin conductance response; interaction dissociation × quadratic time × type, p = 0.009). Specifically, the control group and the BPD D− subgroup showed an increase in valence and arousal to the conditioned stimulus (CS+) during the conditioning procedure (all p < 0.012) and demonstrated differential skin conductance responses in the acquisition and extinction phases. In contrast, the BPD D+ subgroup showed no increase in valence and arousal to CS+ or differential response regarding skin conductance. We examined general psychopathology, trauma history, perceptual differences and posttraumatic stress disorder as confounding factors, but we found no evidence of bias.
Subdividing the BPD group reduced power. In addition, because our sample included only women, the generalizability of our results is constrained. Furthermore, we performed no separate analysis of the influence of different aspects of dissociation on the learning process.
Emotional, amygdala-based learning processes seem to be inhibited during state dissociative experience. State dissociative experience may alter acquisition and extinction processes and should be closely monitored in exposure-based psychotherapy.
PMCID: PMC2674975  PMID: 19448852
20.  Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder 
Psychiatric Genetics  2014;24(6):262-265.
Supplemental Digital Content is available in the text.
The objective of this study was to investigate the hypothesis that borderline personality disorder (BPD) and bipolar disorder (BD) share genetic variation through analysis of known genetic risk factors for BD in a well-characterized BPD case–control cohort. Genotyping of five genome-wide significant variants identified for BD (in CACNA1C, ANK3, and ODZ4) was performed in 673 BPD cases and 748 controls. A nominally significant association with BPD was found for rs1006737 in CACNA1C (P=0.0498). Sex-specific analysis showed that this signal was present only in women. This is the first report of an association between a BD risk gene and BPD where selection was not based on a priori hypotheses about its function, but on an unbiased hypothesis-free screening of the genome. Genome-wide association data of large samples of BPD are warranted and will eventually identify new risk genes and the overlap between BPD and BD if it exists.
PMCID: PMC4219535  PMID: 25304227
bipolar disorder; borderline personality disorder; CACNA1C; comorbidity; genetic overlap

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