Psychobiological Investigation on Sociosexual Behavior in Male: Preclinical and Clinical Studies

The results of several recent epidemiological surveys, shows that male sexual dysfunctions (e.g. erectile dysfunction and premature ejaculation) are extremely prevalent in the general population. These sexual disorders are strongly associated with aging and are influenced by a variety of medical, psychiatric, life style factors and have a significant relationship with mood, state and interpersonal functioning and overall quality of life. An emerging point of view in the last two decade shows that a combination of psychological (e.g. temperamental and personality trait), physiological (e.g. endocrine data) and ecological (e.g. social status) variables seem to be the most relevant factors to explain the develop of this difficulties. Recent epidemiological paper point out the relationships between depression, low dominance score and erectile dysfunctions. In this context, the rank theory of depression (known also as defeat theory or resource loss theory) suggests that depression is highly correlated with perceptions of low rank and subordinate status. In fact depressed people has a degree of inhibition in engagement in certain social activities, see themselves as inferior to others and tend to behave submissively, all variables also associated with anxiety, especially social anxiety as a specific stressor. Under this respect in animal species a recurring factor, as the exposure to chronic social stress has been associated with many systemic and behavioural disorders. However, being exposed to social stress does not necessarily predict subsequent pathological consequences, in fact social factors (i.e. dominance and submission) are a key factor in individual disease susceptibility. The aim of this thesis is to investigate the impact of social stress such as defeat and loss of rank on male mice sexual behavior and tentatively compare preliminary human clinical data supporting the view that loss of resource and/or rank is a critical factor in the development of sexual dysfunction accompanied by depressive state

A Contribution to Validation of the Short Schema Mode Inventory in an Italian Clinical Versus Non-clinical Population

Schema therapy (ST) has been proven to be an effective psychotherapy model in the treatment of complex personality disorders. ST helps analyze causes of emotional, cognitive, and behavioral alteration in patients using schemas and modes (i.e., sets of emotional states, coping responses and schemas active in a given moment). ST finds its empirical validation in the short Schema Mode Inventory (SMI), a practical tool consisting of 14 subscales assessing 14 different mode categories, grouped in 4 (child, coping, parent and adult modes) high-order categories used to assess different modes at different times. We introduced the Italian validation of the short SMI to a sample of 707 participants, of whom 230 were psychiatric patients. Confirmatory factor analysis (CFA) provides evidence that the 14-dimensional model best describes the SMI\u2019s structure at a lower level. Higher-order CFA provides evidence for both four higher-level mode categories and one higher-level mode category, the four-mode category being the best approach. Internal reliability, test\u2013retest stability and the relationship between the SMI\u2019s subscales have been evaluated with promising results. Clinical vs nonclinical subjects were compared with a multigroup CFA in order to test invariance and with a MANOVA and Bonferroni post hoc comparisons in order to test mean differences. A linear thread was found for all modes except Bully/Attack. While contributing to international research and to the diffusion of SMI and schema therapy, our results also suggest that SMI is a powerful tool for the assessment of modes in ST, both in therapeutic and diagnostic contexts

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

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

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

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