Abnormal Brain Circuits Characterize Borderline Personality and Mediate the Relationship between Childhood Traumas and Symptoms: A mCCA+jICA and Random Forest Approach.

Borderline personality disorder (BPD) is a severe personality disorder whose neural bases are still unclear. Indeed, previous studies reported inconsistent findings concerning alterations in cortical and subcortical areas. In the present study, we applied for the first time a combination of an unsupervised machine learning approach known as multimodal canonical correlation analysis plus joint independent component analysis (mCCA+jICA), in combination with a supervised machine learning approach known as random forest, to possibly find covarying gray matter and white matter (GM-WM) circuits that separate BPD from controls and that are also predictive of this diagnosis. The first analysis was used to decompose the brain into independent circuits of covarying grey and white matter concentrations. The second method was used to develop a predictive model able to correctly classify new unobserved BPD cases based on one or more circuits derived from the first analysis. To this aim, we analyzed the structural images of patients with BPD and matched healthy controls (HCs). The results showed that two GM-WM covarying circuits, including basal ganglia, amygdala, and portions of the temporal lobes and of the orbitofrontal cortex, correctly classified BPD against HC. Notably, these circuits are affected by specific child traumatic experiences (emotional and physical neglect, and physical abuse) and predict symptoms severity in the interpersonal and impulsivity domains. These results support that BPD is characterized by anomalies in both GM and WM circuits related to early traumatic experiences and specific symptoms.

Molecular Polymorphisms of Vascular Endothelial Growth Factor Gene and Bronchopulmonary Dysplasia in Very Low Birth Weight Infants.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting primarily preterm and very low birth weight (VLBW) infants. Despite the advances in perinatal care, BPD remains a major clinical and costly complication in premature infants. The pathogenesis of BPD is complex and multifactorial. Prematurity, mechanical ventilation, oxidative stress, and inflammation are recognized as major interrelated contributing factors. Recently, some candidate genes involved in angiogenesis and alveolarization regulating mechanisms have been associated to BPD risk development. The aim of this study was to evaluate the role of vascular endothelial growth factor (VEGF) polymorphisms on BPD onset in VLBW newborns. Methods: Eighty-two VLBW infants, without major anomalies, were consecutively enrolled: 33 developed BPD (BPD group) and 49 infants without BPD served as controls (control group). In all infants, two polymorphisms, respectively (VEGF receptor) VEGFR1-710 C/T and VEGF +936 C/T, were determined through salivary brush. Genomic DNA was extracted and purified from saliva samples by using the MasterAmp Buccal Swab DNA Extraction Kit (Tebu-bio, Milan, Italy). Results: Significant statistic differences were found between BPD newborns and controls with regard to gestational age, birth weight, mechanical ventilation, duration of oxygen therapy, maternal preeclampsia, and chorioamnionitis. No differences were detected between genotypic and allelic levels regarding VEGFR1 and VEGF molecular polymorphisms. Conclusions: Two single nucleotide polymorphisms within VEGF and VEGFR1 genes are not associated with BPD. Further researches are needed to reveal gene polymorphisms involved in vascular development as contributors to the onset of BPD.

Structural Features Predict Sexual Trauma and Interpersonal Problems in Borderline Personality Disorder but Not in Controls: A Multi-Voxel Pattern Analysis.

Child trauma plays an important role in the etiology of Bordeline Personality Disorder (BPD). Of all traumas, sexual trauma is the most common, severe and most associated with receiving a BPD diagnosis when adult. Etiologic models posit sexual abuse as a prognostic factor in BPD. Here we apply machine learning using Multiple Kernel Regression to the Magnetic Resonance Structural Images of 20 BPD and 13 healthy control (HC) to see whether their brain predicts five sources of traumas: sex abuse, emotion neglect, emotional abuse, physical neglect, physical abuse (Child Trauma Questionnaire; CTQ). We also applied the same analysis to predict symptom severity in five domains: affective, cognitive, impulsivity, interpersonal (Zanarini Rating Scale for Borderline Personality Disorder; Zan-BPD) for BPD patients only. Results indicate that CTQ sexual trauma is predicted by a set of areas including the amygdala, the Heschl area, the Caudate, the Putamen, and portions of the Cerebellum in BPD patients only. Importantly, interpersonal problems only in BPD patients were predicted by a set of areas including temporal lobe and cerebellar regions. Notably, sexual trauma and interpersonal problems were not predicted by structural features in matched healthy controls. This finding may help elucidate the brain circuit affected by traumatic experiences and connected with interpersonal problems BPD suffer from.

Is Low Heart Rate Variability Associated with Emotional Dysregulation, Psychopathological Dimensions, and Prefrontal Dysfunctions? An Integrative View.

Several studies have suggested a correlation between heart rate variability (HRV), emotion regulation (ER), psychopathological conditions, and cognitive functions in the past two decades. Specifically, recent data seem to support the hypothesis that low-frequency heart rate variability (LF-HRV), an index of sympathetic cardiac control, correlates with worse executive performances, worse ER, and specific psychopathological dimensions. The present work aims to review the previous findings on these topics and integrate them from two main cornerstones of this perspective: Porges' Polyvagal Theory and Thayer and Lane's Neurovisceral Integration Model, which are necessary to understand these associations better. For this reason, based on these two approaches, we point out that low HRV is associated with emotional dysregulation, worse cognitive performance, and transversal psychopathological conditions. We report studies that underline the importance of considering the heart-brain relation in order to shed light on the necessity to implement psychophysiology into a broader perspective on emotions, mental health, and good cognitive functioning. This integration is beneficial not only as a theoretical ground from which to start for further research studies but as a starting point for new theoretical perspectives useful in clinical practice.

Validation of the Sexual Inhibition/Sexual Excitation Scales (SIS/SES) in Italy: Assessing Gender and Age Differences of Sexual Functioning.

The Sexual Inhibition Scales and Sexual Excitation Scales (Janssen et al., 2002a), based on the dual control model by Bancroft and Janssen (2000), are part of a 45-item self-report questionnaire evaluating individual tendencies to sexual inhibition or excitation according to three factors: two inhibition factors, SIS1, threat of performance failure, and SIS2, threat of performance consequences, and one excitation factor, SES. In this paper, we aimed to validate and explore psychometric properties of the SIS/SES in a sample of 2260 Italian men and women aged 18 to 75 years. Confirmatory factor analyses showed that the three-factor structure proposed in the original version of the scales fit with our sample. Moreover, our data confirmed the results of the original validation sample: Women scored higher on the SIS and lower on the SES than men did, but no significant differences appeared in the factor scores by age group, except for a gender × age interaction, where younger women had higher SIS2 scores. The SIS/SES appeared to be an effective, appropriate cross-cultural measurement of human sexuality in Italian samples, also shedding light on sexual arousal differences in women and men in our country. We also discuss clinical and therapeutic aspects.

Common and different gray and white matter alterations in bipolar and borderline personality disorder: A source-based morphometry study.

According to the nosological classification, Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) are different syndromes. However, these pathological conditions share a number of affective symptoms that make the diagnosis difficult. Affective symptoms range from abnormal mood swings, characterizing both BD and BPD, to regulation dysfunctions, more specific to BPD. To shed light on the neural bases of these aspects, and to better understand differences and similarities between the two disorders, we analysed for the first time gray and white matter features of both BD and BPD. Structural T1 images from 30 patients with BD, 20 with BPD, and 45 controls were analysed by capitalizing on an innovative whole-brain multivariate method known as Source-based Morphometry. Compared to controls, BD patients showed increased gray matter concentration (p = .003) in a network involving mostly subcortical structures and cerebellar areas, possibly related to abnormal mood experiences. Notably, BPD patients showed milder alterations in the same circuit, standing in the middle of a continuum between BD and controls. In addition to this, we found an altered white matter network specific to BPD (p = .018), including frontal-parietal and temporal regions possibly associated with dysfunctional top-down emotion regulation. These findings may shed light on a better understanding of affective disturbances behind the two disorders, with BD patients more characterized by abnormalities in neural structures involved in mood oscillations, and BPD by deficits in the cognitive regulation of emotions. These results may help developing better treatments tailored to the specific affective disturbances displayed by these patients.

A Dual Route Model for Regulating Emotions: Comparing Models, Techniques and Biological Mechanisms.

The aim of this article is to present recent applications of emotion regulation theory and methods to the field of psychotherapy. The term Emotion Regulation refers to the neurocognitive mechanisms by which we regulate the onset, strength, and the eventual expression of our emotions. Deficits in the regulation of emotions have been linked to most, if not all, psychiatric disorders, with patients presenting either dysregulated emotions, or dysfunctional regulatory strategies. We discuss the implications of regulating emotions from two different theoretical perspectives: the Cognitive Emotion Regulation (CER), and the Experiential-Dynamic Emotion Regulation (EDER) model. Each proposes different views on how emotions are generated, dysregulated and regulated. These perspectives directly influence the way clinicians treat such problems. The CER model views emotional dysregulation as due to a deficit in regulation mechanisms that prioritizes modifying or developing cognitive skills, whilst the EDER model posits emotional dysregulation as due to the presence of dysregulatory mechanisms that prioritizes restoring natural regulatory processes. Examples of relevant techniques for each model are presented including a range of cognitive-behavioral, and experiential (including both dynamic and cognitive) techniques. The aim of the paper is to provide a toolbox from which clinician may gain different techniques to enhance and maintain their patient's capacity for emotional regulation. Finally, the biological mechanisms behind the two models of emotion regulation are discussed as well as a proposal of a dual route model of emotion regulation.

Back to Stir It Up: Erectile Dysfunction in an Evolutionary, Developmental, and Clinical Perspective.

In this review, we analyze erectile dysfunction (ED) in the context of sexual selection. We highlight that ED is a specific human male characteristic linked to the loss of the baculum or penile bone and results from a range of physical and psychological factors. We discuss evolutionary interpretations that consider dysfunctional penile erection as an honest signal of a low-quality male. We further emphasize the importance of considering psychosocial context and early attachment dynamics for understanding the etiology of some types of ED. Finally, we suggest that the integration of developmental factors for understanding the emergence of this sexual disorder is instrumental for the calibration of more effective therapies.

Schema therapy for emotional dysregulation in personality disorders: a review.

PURPOSE OF REVIEW: To give an update on the most recent studies regarding the role of schema therapy in the treatment of emotion dysregulation related to personality disorders. RECENT FINDINGS: In personality disorders, a lack of emotion regulation can be found. Schema therapy treats emotion dysregulation with a series of techniques, such as imagery rescripting, limited reparenting, chairwork, and cognitive restructuring to remove dysregulatory mechanism. SUMMARY: Schema therapy is one of the most efficient therapies for personality disorders. However, there is a lack of recent studies on how it treats emotion dysregulation. Although the treatment of emotional dysregulation is not the core of schema therapy, it is certainly important inside this theoretical framework. The mode model helps clinicians address their work toward the reduction of dysfunctional modes, whereas fostering functional modes.

What is stressful for females? Differential effects of unpredictable environmental or social stress in CD1 female mice.

Stressful life events are a major factor in the etiology of several diseases, such as cardiovascular, inflammatory and psychiatric disorders (i.e., depression and anxiety), with the two sexes greatly differing in vulnerability. In humans and other animals, physiological and behavioral responses to stress are strongly dependent on gender, and conditions that are stressful for males are not necessarily stressful for females. Hence the need of an animal model of social chronic stress specifically designed for females. In the present study we aimed to compare the effects of two different chronic stress procedures in female mice, by investigating the impact of 4weeks of nonsocial unpredictable, physical stress by the Chronic Mild Stress paradigm (CMS; Exp.1) or of Social Instability Stress (SIS; Exp.2) on physiological, endocrine and behavioral parameters in adult female mice. CMS had a pronounced effect on females' response to novelty (i.e., either novel environment or novel social stimulus), body weight growth and hormonal profile. Conversely, 4weeks of social instability did not alter females' response to novelty nor hormonal levels but induced anhedonia. Our findings thus showed that female mice were more sensitive to nonsocial stress due to unpredictable physical environment than to social instability stressors. Neither of these stress paradigms, however, induced a consistent behavioral and physiological stress response in female mice comparable to that induced by chronic stress procedures in male mice, thus confirming the difficulties of developing a robust and validated model of chronic psychosocial stress in female mice.

Randomized controlled trial of a book-sharing intervention in a deprived South African community: effects on carer-infant interactions, and their relation to infant cognitive and socioemotional outcome.

BACKGROUND: Consistent with evidence from high-income countries (HICs), we previously showed that, in an informal peri-urban settlement in a low-middle income country, training parents in book sharing with their infants benefitted infant language and attention (Vally, Murray, Tomlinson, & Cooper, ). Here, we investigated whether these benefits were explained by improvements in carer-infant interactions in both book-sharing and non-book-sharing contexts. We also explored whether infant socioemotional development benefitted from book sharing. METHODS: We conducted a randomized controlled trial in Khayelitsha, South Africa. Carers of 14-16-month-old infants were randomized to 8 weeks' training in book sharing (n = 49) or a wait-list control group (n = 42). In addition to the cognitive measures reported previously, independent assessments were made at base line and follow-up of carer-infant interactions during book sharing and toy play. Assessments were also made, at follow-up only, of infant prosocial behaviour in a 'help task', and of infant imitation of doll characters' nonsocial actions and an interpersonal interaction. Eighty-two carer-infant pairs (90%) were assessed at follow-up. (Trial registration ISRCTN39953901). RESULTS: Carers who received the training showed significant improvements in book-sharing interactions (sensitivity, elaborations, reciprocity), and, to a smaller extent, in toy-play interactions (sensitivity). Infants in the intervention group showed a significantly higher rate of prosocial behaviour, and tended to show more frequent imitation of the interpersonal interaction. Improvements in carer behaviour during book sharing, but not during toy play, mediated intervention effects on all infant cognitive outcomes, and tended to mediate intervention effects on infant interpersonal imitation. CONCLUSIONS: Training in book sharing, a simple, inexpensive intervention that has been shown to benefit infant cognitive development in a low-middle income country, also shows promise for improving infant socioemotional outcomes in this context. Benefits are mediated by improvements in carer-infant interactions, particularly in book-sharing contexts.

Schema Therapy for Emotional Dysregulation: Theoretical Implication and Clinical Applications.

The term emotional dysregulation refers to an impaired ability to regulate unwanted emotional states. Scientific evidence supports the idea that emotional dysregulation underlies several psychological disorders as, for example: personality disorders, bipolar disorder type II, interpersonal trauma, anxiety disorders, mood disorders and post-traumatic stress disorder. Emotional dysregulation may derive from early interpersonal traumas in childhood. These early traumatic events create a persistent sensitization of the central nervous system in relation to early life stressing events. For this reason, some authors suggest a common endophenotypical origin across psychopathologies. In the last 20 years, cognitive behavioral therapy has increasingly adopted an interactive-ontogenetic view to explain the development of disorders associated to emotional dysregulation. Unfortunately, standard Cognitive Behavior Therapy (CBT) methods are not useful in treating emotional dysregulation. A CBT-derived new approach called Schema Therapy (ST), that integrates theory and techniques from psychodynamic and emotion focused therapy, holds the promise to fill this gap in cognitive literature. In this model, psychopathology is viewed as the interaction between the innate temperament of the child and the early experiences of deprivation or frustration of the subject's basic needs. This deprivation may lead to develop early maladaptive schemas (EMS), and maladaptive Modes. In the present paper we point out that EMSs and Modes are associated with either dysregulated emotions or with dysregulatory strategies that produce and maintain problematic emotional responses. Thanks to a special focus on the therapeutic relationship and emotion focused-experiential techniques, this approach successfully treats severe emotional dysregulation. In this paper, we make several comparisons between the main ideas of ST and the science of emotion regulation, and we present how to conceptualize pathological phenomena in terms of failed regulation and some of the ST strategies and techniques to foster successful regulation in patients.

Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice.

Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders.

Sildenafil counteracts the inhibitory effect of social subordination on competitive aggression and sexual motivation in male mice.

The effects of chronic intra-peritoneal administration of 10 mg/kg (t.i.w., for 5 weeks) of sildenafil on competitive aggression, sexual behaviour and body weight gain was tested in CD1 subordinate male mice in two experimental contexts: 1) "low levels of aggression", i.e. housing in dyads of siblings 2) "high levels of aggression", i.e. exposure to a model of chronic psychosocial stress with an unfamiliar mice. Subordinate mice in both experimental contexts were injected with sildenafil or saline. After 2 weeks of sildenafil administration, a subgroup of subordinates exposed to "high levels of aggression" began to counterattack their dominant counterparts at higher rates than saline-injected subordinates. This effect was essentially similar but faster in subordinates subjected to "low levels of aggression". As far as sexual behaviour is concerned, in both experimental contexts, sildenafil-injected subordinated mice showed significant lower latencies to mount a proceptive female when compared to saline-injected subjects. Furthermore, in the "high levels of aggression" context, Sildenafil reduced stress-induced body weight gain. Sildenafil showed no effects in individually housed males serving as controls. In conclusion, chronic Sildenafil treatment counteracts the inhibitory effects of social subordination on male competitive aggression, sexual behaviour and body weight gain. Overall our data suggests that sildenafil could be acting in the central nervous system to modulate sexual and agonistic motivation.

Personality traits and endocrine response as possible asymmetry factors of agonistic outcome in karate athletes.

Individual variations of plasma levels of hormones testosterone (T) and cortisol (C), before (pre) and after (post) Kumite (real fight) and Kata (ritualized fight) were measured in male karate athletes and analyzed in relation with the agonistic outcome (i.e. winning or losing the fight) and personality trait measures. T and C increased only during Kumite contest and pre- and post-competition C levels were higher in losers than winners. Losers showed higher levels of harm avoidance and anxiety as well as lower level of novelty seeking than winners. Importantly, novelty seeking negatively correlates with pre C and the higher the level of risk assessment, emotionality and insecurity indexes the higher the pre C level. In conclusion, personality traits might be an important factor asymmetry between athletes influencing both the probability of winning or losing an agonistic interaction and the different anticipatory endocrine response to the incipient fight.

Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress.

Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1) opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2) a reduction in body weight in individually housed (Ind) male mice. In the present study these observations were extended to provide a comprehensive characterization of the metabolic consequences of chronic psychosocial stress and individual housing in adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant (Dom) and Ind had a negative energy balance while subordinate (Sub) had a positive energy balance. Locomotor activity was depressed in Sub and enhanced in Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed a consistent decrease of visceral fat pads weight as well as increased norepinephrine concentration and smaller adipocytes diameter in the perigonadal fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed higher while Dom showed lower vulnerability to obesity associated with hyperphagia. In conclusion, we demonstrated that social status under chronic stress and individual housing deeply affect mice metabolic functions in different, sometime opposite, directions. Food intake, the hedonic response to palatable food as well as the locomotor activity and the sympathetic activation within the adipose fat pads all represent causal factors explaining the different metabolic alterations observed. Overall this study demonstrates that pre-clinical animal models offer a suitable tool for the investigation of the metabolic consequences of chronic stress exposure and associated psychopathologies.