Affect in response to stressors and coping strategies: an ecological momentary assessment study of borderline personality disorder

Background: Affect instability is a core symptom of borderline personality disorder (BPD). Ecological momentary assessment allows for an understanding of real-time changes in affect in response to various daily stressors. The purpose of this study was to explore changes in affect in response to specific stressors and coping strategies in subjects with BPD utilizing ecological momentary assessment (EMA) methodology. Methods: Subjects (n = 50) with BPD were asked to complete real-time assessments about stressors experienced, affect felt, and coping strategies employed six times per day for a 1-week period. Mixed effect regression models were used to measure the effect of stressors and coping strategies on affect change. Results: While most stressors led to experiencing more negative affect, only being in a disagreement was independently associated with increased negative affect. Among coping strategies, only doing something good for oneself independently reduced negative affect, controlling for all other coping strategies used. Conclusions: These findings provide valuable insights into affective instability in BPD and can help inform treatment with individuals with the disorder

Shared risk factors for mood-, eating-, and weight-related health outcomes.

Objective: Given the overlap among depressive symptoms, disordered eating, and overweight, identifying shared risk factors for these conditions may inform public health interventions. This study aimed to examine cross-sectional and prospective relationships among these 3 conditions, and identify potential shared eating-related and psychosocial variable risk factors (i.e., body dissatisfaction, dieting, teasing experiences). Method: A population-based sample (n = 1,902) self-reported depressive symptoms, disordered eating (binge eating, extreme weight control behaviors), weight status, and several putative risk factors (body satisfaction, dieting frequency, weight-related teasing) at 5-year intervals spanning early/middle adolescence, middle adolescence/early young adulthood, and early/middle young adulthood. Results: There was moderate overlap among depressive symptoms, disordered eating, and overweight at each time point, and moderate stability in each condition over time. Body dissatisfaction and dieting were the most potent shared risk factors for later depressive symptoms, disordered eating, and overweight among males and females (ps \u3c .05). Conclusions: Depressive symptoms, disordered eating, and overweight share several risk factors, including dieting and body dissatisfaction, which may be effective targets for interventions aiming to simultaneously prevent these 3 conditions

A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms.

Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients

A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms

Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients. Keywords: Ketamine, Functional connectivity, Psychosis, Resting stat

Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial.

Importance:Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation for glutamate-based treatment development is the lack of functional target-engagement biomarkers for translation between preclinical and early-stage clinical studies. We evaluated the utility of 3 potential biomarkers-ketamine-evoked changes in the functional magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD), glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI-for detecting ketamine-related alterations in brain glutamate. Objective:To identify measures with sufficient effect size and cross-site reliability to serve as glutamatergic target engagement biomarkers within early-phase clinical studies. Design, Setting, and Participants:This randomized clinical trial was conducted at an academic research institution between May 2014 and October 2015 as part of the National Institute of Mental Health-funded Fast-Fail Trial for Psychotic Spectrum Disorders project. All raters were blinded to study group. Healthy volunteers aged 18 to 55 years of either sex and free of significant medical or psychiatric history were recruited from 3 sites. Data were analyzed between November 2015 and December 2016. Interventions:Volunteers received either sequential ketamine (0.23 mg/kg infusion over 1 minute followed by 0.58 mg/kg/h infusion over 30 minutes and then 0.29 mg/kg/h infusion over 29 minutes) or placebo infusions. Main Outcomes and Measures:Ketamine-induced changes in pharmacoBOLD, 1H MRS, and task-based fMRI measures, along with symptom ratings. Measures were prespecified prior to data collection. Results:Of the 65 volunteers, 41 (63%) were male, and the mean (SD) age was 31.1 (9.6) years; 59 (91%) had at least 1 valid scan. A total of 53 volunteers (82%) completed both ketamine infusions. In pharmacoBOLD, a highly robust increase (Cohen d = 5.4; P < .001) in fMRI response was observed, with a consistent response across sites. A smaller but significant signal (Cohen d = 0.64; P = .04) was also observed in 1H MRS-determined levels of glutamate+glutamine immediately following ketamine infusion. By contrast, no significant differences in task-activated fMRI responses were found between groups. Conclusions and Relevance:These findings demonstrate robust effects of ketamine on pharmacoBOLD across sites, supporting its utility for definitive assessment of functional target engagement. Other measures, while sensitive to ketamine effects, were not sufficiently robust for use as cross-site target engagement measures. Trial Registration:clinicaltrials.gov Identifier: NCT02134951