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.