Brain structural anomalies in borderline and avoidant personality disorder patients and their associations with disorder-specific symptoms.

BACKGROUND: Borderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature. METHODS: In the present study we investigated group differences among 29 BPD patients, 27 AvPD patients, and 29 healthy controls (HC) in structural brain volumes using voxel-based morphometry (VBM) in five anatomically-defined regions of interest: amygdala, hippocampus, medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). We also examined the relationship between individual differences in brain structure and self-reported anxiety and affective instability in each group. RESULTS: We observed reductions in MPFC and ACC volume in BPD relative to HC, with no significant difference among patient groups. No group differences in amygdala volume were found. However, BPD and AvPD patients each showed a positive relationship between right amygdala volume and state-related anxiety. By contrast, in HC there was an inverse relationship between MPFC volume and state and trait-related anxiety as well as between bilateral DLPFC volume and affective instability. LIMITATIONS: Current sample sizes did not permit examination of gender effects upon structure-symptom correlations. CONCLUSIONS: These results shed light on potentially protective, or compensatory, aspects of brain structure in these populations-namely, relatively reduced amygdala volume or relatively enhanced MPFC and DLPFC volume.

Elevated amygdala activity during reappraisal anticipation predicts anxiety in avoidant personality disorder.

BACKGROUND: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplored question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli. METHODS: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, self-reported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task. RESULTS: Avoidant patients showed greater state and trait-related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyper-reactivity during reappraisal anticipation, and this hyper-reactivity effect was positively associated with increasing self-reported anxiety levels. LIMITATIONS: Our finding of exaggerated amygdala activity during reappraisal anticipation could reflect anxiety about the impending need to reappraise, anxiety about the certainty of an upcoming negative image, or anxiety relating to anticipated scrutiny of task responses by the experimenters. While we believe that all of these possibilities are consistent with the phenomenology of avoidant personality disorder, future research may clarify this ambiguity. CONCLUSIONS: These results suggest that amygdala reactivity in anticipation of receiving negative social information may represent a key component of the neural mechanisms underlying the heightened anxiety present in avoidant patients.

Insula-amygdala functional connectivity is correlated with habituation to repeated negative images.

Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging. We were particularly interested in investigating patterns of activity in insula, given its significant role in affective integration, and in amygdala, given its association with appraisal of aversive stimuli and its frequent coactivation with insula. We found significant habituation behaviorally along with decreases in amygdala, occipital cortex and ventral prefrontal cortex (PFC) activity with repeated presentation, whereas bilateral posterior insula, dorsolateral PFC and precuneus showed increased activation. Posterior insula activation during image presentation was correlated with greater negative affect ratings for novel presentations of negative images. Further, repeated negative image presentation was associated with increased functional connectivity between left posterior insula and amygdala, and increasing insula-amygdala functional connectivity was correlated with increasing behavioral habituation. These results suggest that habituation is subserved in part by insula-amygdala connectivity and involves a change in the activity of bottom-up affective networks.

The neural correlates of anomalous habituation to negative emotional pictures in borderline and avoidant personality disorder patients.

OBJECTIVE: Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder. METHOD: During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups. RESULTS: Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation. CONCLUSIONS: Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients.

Platelet protein kinase C and brain-derived neurotrophic factor levels in borderline personality disorder patients.

Borderline personality disorder (BPD) is a prevalent and difficult to treat psychiatric condition characterized by abrupt mood swings, intense anger and depression, unstable interpersonal relationships, impulsive self-destructive behavior and a suicide rate of approximately 10%. Possible underlying molecular dysregulations in BPD have not been well explored. Protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) have both been implicated in affective disorders, but their role in BPD has not been examined. Platelets were isolated from blood obtained from 24 medication-free BPD patients and 18 healthy control subjects. PKC-α, phosphorylated-PKC-α (p-PKCα), PKC-ßII, and BDNF were measured in platelet homogenates by immunoblotting. In the males, platelet BDNF and PKC-α levels were lower in patients than controls. p-PKC-α and PKC-ßII were lower at trend levels. In the entire sample, platelet p-PKCα and PKC-α activity were lower, at a trend level, in patients compared to controls. This is the first report to our knowledge of PKC and BDNF activity in BPD and calls for replication. These findings are consistent with altered PKC and BDNF activity in a range of neuropsychiatric conditions including bipolar disorder, depression and suicide.

Neural correlates of using distancing to regulate emotional responses to social situations.

Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one's self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation.

Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder.

BACKGROUND: Emotional instability is a defining feature of borderline personality disorder (BPD); yet, little is understood about its underlying neural correlates. One possible contributing factor to emotional instability is a failure to adequately employ adaptive cognitive regulatory strategies such as psychological distancing. METHODS: To determine whether there are differences in neural dynamics underlying this control strategy between BPD patients and healthy control (HC) subjects, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging signals were acquired as 18 BPD and 16 HC subjects distanced from or simply looked at pictures depicting social interactions. Contrasts in signal between distance and look conditions were compared between groups. RESULTS: Borderline personality disorder patients showed a different pattern of activation compared with HC subjects when looking at negative versus neutral pictures. When distancing versus looking at negative pictures, both groups showed decreased negative affect ratings and increased activation of the dorsolateral prefrontal cortex, areas near/along the intraparietal sulcus (IPS), ventrolateral prefrontal cortex, and posterior cingulate/precuneus regions. However, the BPD group showed less BOLD signal change in dorsal anterior cingulate cortex and IPS, less deactivation in the amygdala, and greater activation in the superior temporal sulcus and superior frontal gyrus. CONCLUSIONS: Borderline personality disorder and HC subjects display different neural dynamics while passively viewing social emotional stimuli. In addition, BPD patients do not engage the cognitive control regions to the extent that HCs do when employing a distancing strategy to regulate emotional reactions, which may be a factor contributing to the affective instability of BPD.