Earliest symptoms discriminating juvenile-onset bipolar illness from ADHD.

OBJECTIVES: Controversy surrounds the diagnosis and earliest symptoms of childhood-onset bipolar illness, emphasizing the importance of prospective longitudinal studies. To acquire a preliminary, more immediate view of symptom evolution, we examined the course of individual symptoms over the first 10 years of life in juvenile-onset bipolar illness (JO-BP) compared with attention-deficit hyperactivity disorder (ADHD). METHODS: Parents of formally diagnosed children retrospectively rated 37 symptoms in each year of the child's life based on the degree of dysfunction in their child's usual family, social, or educational roles. A subset of children with onset of bipolar disorder prior to age 9 (JO-BP) compared with those with ADHD was the focus of this analysis. RESULTS: Brief and extended periods of mood elevation and decreased sleep were strong early differentiators of JO-BP and ADHD children. Depressive and somatic symptoms were later differentiators. Irritability and poor frustration tolerance differentiated the two groups only in their greater incidence and severity in JO-BP compared with a moderate occurrence in ADHD. In contrast, hyperactivity, impulsivity, and decreased attention showed highly similar trajectories in the two groups. CONCLUSIONS: Elevated mood and decreased sleep discriminated JO-BP and ADHD as early as age 3, while classic ADHD symptoms were parallel in the groups. These retrospective results provide preliminary insights into symptom differences and their temporal evolution between bipolar disorder and ADHD in the first 10 years of life.

Neural correlates of emotion processing in borderline personality disorder.

Emotional instability is a hallmark feature of borderline personality disorder (BPD), yet its biological underpinnings are poorly understood. We employed functional magnetic resonance imaging (fMRI) to compare patterns of regional brain activation in BPD patients and healthy volunteers as they process positive and negative social emotional stimuli. fMRI images were acquired while 19 BPD patients and 17 healthy controls (HC) viewed emotion-inducing pictures from the International Affective Pictures System set. Activation data were analyzed with SPM5 ANCOVA models to derive the effects of diagnosis and stimulus type. BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared with rest, in the amygdala, fusiform gyrus, primary visual areas, superior temporal gyrus (STG), and premotor areas, while healthy controls showed greater differences than BPD patients in the insula, middle temporal gyrus and dorsolateral prefrontal cortex (BA46). When viewing positive pictures compared with rest, BPD patients showed greater differences in the STG, premotor cortex, and ventrolateral prefrontal cortex. These findings suggest that BPD patients show greater amygdala activity and heightened activity of visual processing regions relative to findings for HC subjects in the processing of negative social emotional pictures compared with rest. The patients activate neural networks in emotion processing that are phylogeneticall older and more reflexive than those activated by HC subjects.

Peer substance use associated with the co-occurrence of borderline personality disorder features and drug use problems in college students.

OBJECTIVE: To determine if the substance use patterns of one's close friends and romantic partners would be a significant contributor to the co-occurrence of borderline personality disorder (BPD) features and drug use problems above and beyond impulsivity and negative emotionality. PARTICIPANTS: Participants were 2,202 undergraduates who attended a large southeastern university between 2003 and 2006. METHODS: All subjects completed measures assessing the presence of BPD symptoms, drug use problems, general personality traits, and the proportion of their friends and partners who had used illicit drugs within the past 12 months. RESULTS: The illicit drug use patterns of one's friends and romantic partners was a significant contributor to the co-occurrence of BPD features and drug use problems even when controlling for levels of impulsivity and negative emotionality. CONCLUSIONS: These findings suggest possible additional avenues for treatment focusing on helping students with BPD and drug use problems modify their social group.

Support for Linehan's biosocial theory from a nonclinical sample.

Linehan's biosocial theory of borderline personality disorder (BPD) was tested in a sample of 1,044 female college students. Relationships between self-reported BPD symptoms, two personality traits (negative emotionality and constraint), and three key variables from the biosocial theory (emotional vulnerability, invalidation, and emotional dysregulation) were examined using structural equation modeling. Consistent with the biosocial theory, the best fitting model indicated that emotional vulnerability and emotional dysregulation were uniquely related to BPD symptoms after controlling for personality traits, and that dysregulation mediated the relationship between emotional vulnerability and BPD. However, invalidation was not significantly associated with BPD and could be dropped from that model. The full model with Linehan's constructs and personality traits explained 58% of the variance in BPD and, as expected, explained considerably less variance in symptoms of other Cluster B PDs. The present results highlight the incremental value of the Linehan's theory and its specificity to BPD.

Complexity of pharmacologic treatment required for sustained improvement in outpatients with bipolar disorder.

OBJECTIVE: To evaluate the clinical correlates of and types of naturalistic treatments associated with sustained improvement/remission for at least 6 months in outpatients with bipolar disorder. METHOD: Five hundred twenty-five outpatients with bipolar disorder (77.7% bipolar I) gave informed consent, had their mood rated daily on the National Institute of Mental Health Life Chart Method for a minimum of at least 1 year, and recorded all medications. Demographics and clinical characteristics of patients with a "sustained response" (ratings of "improved" or "very much improved" on the Clinical Global Impressions-Bipolar Version for a period of at least 6 months) versus nonresponders were compared. The study was conducted from 1996 to 2002. RESULTS: Of the 429 patients who were ill at study entry, 195 (45.5%) showed a sustained response; 54.5% showed no or insufficient response. A mean of 2.98 medications was given at time of improvement, which occurred after a mean of 18 months of participation in the study. Lithium and valproate were the medications most frequently prescribed at the time of improvement and had among the highest overall success rates. Equally complex regimens were employed in the nonresponders who, however, had a more adverse clinical course prior to network entry. Nonresponders were ultimately exposed to more antidepressants and antipsychotics than the sustained responders. CONCLUSIONS: A mean of 1.5 years and at times highly complex medication regimens were required to achieve a sustained response for 6 months during naturalistic outpatient treatment of bipolar disorder. Delineating the clinical and biologic correlates of individual response to combination treatment is a very high clinical research priority, as is developing new treatment strategies for the large proportion of patients who fail to respond in a sustained fashion.

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.