Autonomic and brain morphological predictors of stress resilience

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stres

First Evaluation of an Index of Low Vagally-Mediated Heart Rate Variability as a Marker of Health Risks in Human Adults: Proof of Concept.

Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we sought to identify a cut point-value for HRV that is associated with elevated risk across a range of known risk factors. METHODS:A total of 9550 working adults from 19 study sites took part in a health assessment that included measures of inflammation, hyperglycemia, hyperlipidemia, and hypertension and vagally-mediated HRV (Root mean square of successive differences between normal heartbeats (RMSSD)). Multiple age and sex adjusted logistic regressions were calculated per risk factor (normal versus clinical range), with RMSSD being entered in binary at different cut points ranging from 15-39 msec with a 2 msec increment. RESULTS:For daytime RMSSD, values below 25 ± 4 indicated elevated risk (odds ratios (OR) 1.5-3.5 across risk factors). For nighttime RMSSD, values below 29 ± 4 indicated elevated risk (OR 1.2-2.0). CONCLUSION:These results provide the first evidence that a single value of RMSSD may be associated with elevated risk across a range of established cardiovascular risk factors and may present an easy to assess novel marker of cardiovascular risk

Resting State Vagally-Mediated Heart Rate Variability Is Associated With Neural Activity During Explicit Emotion Regulation

Resting state vagally mediated heart rate variability (vmHRV) is related to difficulties in emotion regulation (ER). The prefrontal cortex (PFC) provides inhibitory control over the amygdala during ER. Previous studies linked vmHRV with activity in the ventromedial PFC (vmPFC) during implicit ER. To date no study examined the relation between vmHRV and brain activity during explicit ER. vmHRV was measured during a 7 min baseline at T1 2–5 days preceding T2. At T2 n = 24 participants (50% female, Mage = 24.6 years) viewed neutral or emotional pictures of pleasant or unpleasant valence and were instructed to intensify or to reduce their present emotion using two ER strategies (reappraisal and responsemodulation) or to passively view the picture. Participants rated the valence of their emotional state from pleasant to unpleasant after ER. Whole-brain fMRI data were collected using a 1.5-T-scanner. We observed an association between resting state vmHRV and brain activation in the PFC and the amygdala during ER of unpleasant emotions. Groups based on vmHRV showed significant differences in the modulation of amygdala activity as a function of ER strategy. In participants with high vmHRV amygdala activity was modulated only when using reappraisal and for low vmHRV participants only when using response modulation. Similar, dorsomedial PFC activity in high vmHRV participants was increased when using reappraisal and in low vmHRV participants when using response modulation to regulate unpleasant emotions. These results suggest that individuals with low vmHRV might have difficulties in recruiting prefrontal brain areas necessary for the modulation of amygdala activity during explicit ER

Health related quality of life and psychopathological distress in risk taking and self-harming adolescents with full-syndrome, subthreshold and without borderline personality disorder: rethinking the clinical cut-off?

Background: Diagnostic standards do not acknowledge developmental specifics and differences in the clinical presentation of adolescents with borderline personality disorder (BPD). BPD is associated with severe impairments in health related quality of life (HRQoL) and increased psychopathological distress. Previously no study addressed differences in HRQoL and psychopathology in adolescents with subthreshold and full-syndrome BPD as well as adolescents at-risk for the development but no current BPD. Methods: Drawing on data from a consecutive sample of N = 264 adolescents (12–17 years) presenting with risk-taking and self-harming behavior at a specialized outpatient clinic, we investigated differences in HRQoL (KIDSCREEN-52) and psychopathological distress (SCL-90-R) comparing adolescents with no BPD (less than 3 criteria fulfilled), to those with subthreshold (3–4 BPD criteria) and full-syndrome BPD (5 or more BPD criteria). Group differences were analyzed using one-way analysis of variance with Sidak corrected contrasts or Chi-Square test for categorical variables. Results: Adolescents with subthreshold and full-syndrome BPD presented one year later at our clinic and were more likely female. Adolescents with subthreshold and full-syndrome BPD showed greater Axis-I and Axis-II comorbidity compared to adolescents with no BPD, and reported greater risk-taking behaviour, self-injury and suicidality. Compared to those without BPD, adolescents with subthreshold and full-syndrome BPD reported significantly reduced HRQoL. Adolescents with sub-threshold BPD and those with full-syndrome BPD did not differ on any HRQoL dimension, with the exception of Self-Perception. Similar, groups with sub-threshold and full-syndrome BPD showed no significant differences on any dimension of self-reported psychopathological distress, with the exception of Hostility. Conclusions: Findings highlight that subthreshold BPD in adolescents is associated with impairments in HRQoL and psychopathological distress comparable to full-syndrome BPD. Findings raise awareness on the importance of early detection and question the diagnostic validity and clinical utility of existing cut-offs. Findings support a lower diagnostic cut-off for adolescent BPD, to identify those at-risk at an early stage

Single Vector System for Efficient N-myristoylation of Recombinant Proteins in E. coli

Background: N-myristoylation is a crucial covalent modification of numerous eukaryotic and viral proteins that is catalyzed by N-myristoyltransferase (NMT). Prokaryotes are lacking endogeneous NMT activity. Recombinant production of N-myristoylated proteins in E. coli cells can be achieved by coexpression of heterologous NMT with the target protein. In the past, dual plasmid systems were used for this purpose. Methodology/Principal Findings: Here we describe a single vector system for efficient coexpression of substrate and enzyme suitable for production of co- or posttranslationally modified proteins. The approach was validated using the HIV-1 Nef protein as an example. A simple and efficient protocol for production of highly pure and completely N-myristoylated Nef is presented. The yield is about 20 mg myristoylated Nef per liter growth medium. Conclusions/Significance: The single vector strategy allows diverse modifications of target proteins recombinantly coexpressed in E. coli with heterologous enzymes. The method is generally applicable and provides large amounts o

Altered Resting-State Networks in Adolescent Non-Suicidal Self-Injury – A Graph Theory Analysis

Non-suicidal self-injury (NSSI) is a highly prevalent transdiagnostic symptom and risk marker for mental health problems among adolescents. Research on the neurobiological mechanisms underlying NSSI is needed to clarify the neural correlates associated with the behavior. We examined resting-state-functional-connectivity (RSFC) in n = 33 female adolescents aged 12-17 years engaging in NSSI, and n = 29 age-matched healthy controls using graph theory. Mixed linear models were evaluated with the Bayes Factor (BF) to determine group differences on global and regional network measures and associations between network measures and clinical characteristics in patients. Adolescents engaging in NSSI demonstrated longer average characteristic path lengths and a smaller number of weighted hubs globally. Regional measures indicated lower efficiency and worse integration in (orbito)frontal regions and higher weighted coreness in the pericalcarine gyrus. In patients, higher orbitofrontal weighted local efficiency was associated with NSSI during the past month while lower pericalcarine nodal efficiency was associated with suicidal thoughts in the past year. Higher right but lower left pericalcarine weighted hubness was associated with more suicide attempts during the past year. Using a graph-based technique to identify functional connectivity networks, this study adds to the growing understanding of the neurobiology of NSSI

Differential outcomes of outpatient only versus combined inpatient/outpatient treatment in early intervention for adolescent borderline personality disorder.

Clinical guidelines for adults with borderline personality disorder (BPD) recommend outpatient psychotherapy as first-line treatment. Little is known whether this recommendation is also applicable to adolescents. The current study examined the relationship between treatment setting and the outcome of early intervention for adolescents with BPD pathology. One-hundred and seventy-eight adolescents from a specialized outpatient clinic were assessed at baseline, and at 1- and 2-year follow-up. Sixty-three participants who received inpatient treatment during the first year were assigned to the "combined inpatient/outpatient group", 115 participants to the "outpatient only group". Generalized linear and mixed models with inverted probability weights to adjust for baseline differences were applied to examine the impact of group on clinical changes over time. Both groups demonstrated a significant decrease in BPD features, depressive symptoms, psychopathological distress, non-suicidal self-injury (NSSI), suicidal thoughts, suicide attempts, and overall illness severity, and a significant increase in quality of life and psychosocial functioning from baseline to follow-up 2. The decrease in NSSI and overall illness severity, and the increase in psychosocial functioning from baseline to follow-up 1 were greater in the outpatient only group, with comparable improvements between groups from follow-up 1 to follow-up 2. Both outpatient treatment and combined outpatient/inpatient treatment resulted in clinical improvements over time, with some indication for faster changes in the outpatient only setting. The findings provide preliminary evidence that the recommendation of outpatient psychotherapy as the first-line treatment for BPD also holds true for adolescents

Psychosocial functioning in adolescents with non-suicidal self-injury: the roles of childhood maltreatment, borderline personality disorder and depression

Background: There is a lack of studies examining psychosocial functioning in patients with non-suicidal self-injury (NSSI), especially in adolescents, and rates of impaired functioning in existing literature vary considerably. These variations may be attributable to further risk factors that influence psychosocial functioning. Thus, the aim of the study was to examine whether adolescent NSSI patients with childhood maltreatment (CM), a known risk factor for lower psychosocial functioning, may differ from adolescent NSSI patients without CM, and whether these differences may be explained by the severity of comorbid disorders. Specifically, we examined whether severity of borderline personality disorder (BPD), depression and posttraumatic stress disorder may explain differences in psychosocial functioning in NSSI patients with and without CM. Methods: Data of 368 adolescents with NSSI disorder from an outpatient clinic were analyzed using structural equation modeling. Clinicans' rating of the Global Assessment of Functioning Scale (GAF) was collected, in addition to clinical interviews. Results: Results indicate that GAF scores were lower among NSSI patients with CM and that the difference in psychosocial functioning between these groups was explained by BPD and depression severity. Conclusions: Psychosocial functioning in NSSI patients varies depending on whether they have experienced CM or not. Specifically, these differences seem to be attributable to higher BPD and depression severity in adolescent NSSI patients with CM. Clinicians should ensure to assess CM and focus on BPD and depression severity in this population. Treatment of BPD and depression may notably reduce psychosocial impairment in NSSI patients with CM

From quasi‐hereditary algebras with exact Borel subalgebras to directed bocses

Up to Morita equivalence, every quasi-hereditary algebra is the dual algebra of a directed bocs or coring. From the bocs, an exact Borel subalgebra isobtained. In this paper a characterisation of exact Borel subalgebras arising in this way is given