Neurological and Mental Disorders

Mental disorders can result from disruption of neuronal circuitry, damage to the neuronal and non-neuronal cells, altered circuitry in the different regions of the brain and any changes in the permeability of the blood brain barrier. Early identification of these impairments through investigative means could help to improve the outcome for many brain and behaviour disease states.The chapters in this book describe how these abnormalities can lead to neurological and mental diseases such as ADHD (Attention Deficit Hyperactivity Disorder), anxiety disorders, Alzheimer’s disease and personality and eating disorders. Psycho-social traumas, especially during childhood, increase the incidence of amnesia and transient global amnesia, leading to the temporary inability to create new memories.Early detection of these disorders could benefit many complex diseases such as schizophrenia and depression

Master of Science

thesisThe current study was designed to examine biosocial correlates of identity disturbance in a sample of suicidal youth at high risk for borderline personality disorder compared with community controls. We used a multimethod, multi-informant design to examine vulnerability and risk for identity disturbance, including biological assessments, self- and informant-report. Participants' electrodermal responding (EDR), respiratory sinus arrhythmia (RSA), and fundamental frequency were collected during a motherchild discussion task regarding adolescents' personality characteristics. We predicted (1) suicidal adolescents would endorse greater overall identity distress across more domains compared with community controls, and (2) that biological vulnerabilities (e.g., EDR, RSA) and contextual risks (e.g., parent emotional arousal assessed with digital signal processing) would interact to predict higher self-reported identity distress among suicidal adolescents. Results indicate significant differences on identity scales for control and self-injuring adolescents. However, indices of biological and contextual risk did not interact to predict identity problems. Methodological limitations of the current study are discussed, along with implications for future research

EEG analytics for early detection of autism spectrum disorder: a data-driven approach

Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.This research was supported by National Institute of Mental Health (NIMH) grant R21 MH 093753 (to WJB), National Institute on Deafness and Other Communication Disorders (NIDCD) grant R21 DC08647 (to HTF), NIDCD grant R01 DC 10290 (to HTF and CAN) and a grant from the Simons Foundation (to CAN, HTF, and WJB). We are especially grateful to the staff and students who worked on the study and to the families who participated. (R21 MH 093753 - National Institute of Mental Health (NIMH); R21 DC08647 - National Institute on Deafness and Other Communication Disorders (NIDCD); R01 DC 10290 - NIDCD; Simons Foundation)Published versio

Mental Representations, Social Exclusion, And Neurobiological Processes In Borderline Personality Disorder: A Multi-Level Study

Borderline Personality Disorder (BPD) is an ongoing public health crisis. Poor developmental quality of differentiation-relatedness of object representations and attachment insecurity have been clinically and empirically demonstrated as core patterns of intrapsychic and interpersonal dysfunction in this particular form of personality pathology. Differentiation-relatedness (D-R), which involves a complementary relationship between intrapsychic autonomy and interpersonal relatedness, has been shown to be a significant aspect of internal psychic experience that relates directly to external relationship patterns, including characteristic response to interpersonal interactions and has been a specific target for treatment of BPD. Specifically, individuals with BPD have shown lower developmental quality of differentiation-relatedness than non-clinical controls. Similarly, attachment insecurity, stemming from repetitive, conflicted exchanges with caregivers beginning from early development, is a hallmark of borderline personality. Although differentiation-relatedness and attachment organization have been extensively studied in this clinical population, few studies have investigated the relationship between such measures of historically relevant intrapsychic functioning, behavioral and neural responses to social interaction in the here and now. Through narrative responses to a clinical interview, self-reports and a measure of social cognition during fMRI that operationalize borderline pathology in distinct ways, this study investigated differences between individuals diagnosed with BPD and non-clinical controls, as well as the relationship among measures of developmental quality of differentiation-relatedness of object representations, attachment style, and behavioral and neural response patterns in a laboratory-based design. Results: Independent samples t-tests showed significant differences between borderline patients and controls for D-R mean, father, and self scores, attachment anxiety and avoidance, and anger response patterns to experiences of social exclusion. Simple linear regression analyses demonstrated that D-R mean, father, and self scores also significantly predicted anger response in Cyberball. Non-significant positive trends for attachment anxiety, scored from the self-report Experience in Close Relationships (ECR) measure, predicting rejection and anger were also evident; however the ECR was less sensitive at predicting rejection and anger in response to social exclusion than D-R scores. The D-R mean score also modulated neural activity associated with social inclusion in Cyberball in the left inferior frontal cortex. Thus, this study provides further evidence of the multidimensional nature of borderline personality disorder and the intricate complexity of the relationship among different levels of the pathology (i.e., intrapsychic, attachment, behavioral, and neural). These results, in conjunction with further studies on the relationship among these components, have the potential to offer crucial insights for the treatment of this disorder

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study

Introduction: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high- order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm. Methods and analysis: Help-seeking young people presenting psychological distress (CHARMS+/− and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa—IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department—territorial mental services (ASL 3—Genoa), Genoa, Italy; and Mental Health Department—territorial mental services (AUSL—Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech. Ethics and dissemination: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020—id.10993; Comitato Etico dell’Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer- reviewed journals, to ensure proper data reproducibility. Trial registration number DOI:10.17605/OSF.IO/BQZTN

A systematic evidence synthesis of the changes observed in the brain of people diagnosed with a personality disorder in Black, Asian and ethnic minority communities

Preface: The path of this research stemmed from a passion and curiosity for mental health and neuroscience and in addition to this how prevalence, aetiology, diagnosis and treatment differs for people from Black, Asian and ethnic minority groups (BAME), being from this community myself. This study was meant to be an empirical study retrieving data from several mental health units in London, who agreed access, only to withdraw it at the last minute. We then planned for outpatients to come to LSBU to have the EEG scans necessary for data collection, but Covid-19 arrived and all face-to-face contact for research purposes halted before any data could be collected. The team concluded, that in order to keep the MRes ‘on the road’ and with no foreseeable end in sight to the CV-19-related lockdown, that a systematic evidence synthesis was feasible. Hence the work being reported here. This Evidence synthesis has been benchmarked against the PRIMSA statement . The associated PRISMA checklist was used to ensure that all relevant PRISMA items were addressed in the review paper, the student’s assessment of this can be found in appendix

A multidimensional developmental neuropsychological model of borderline personality disorder (BPD): examining evidence for impairments in 'executive function'

Borderline Personality Disorder (BPD) is a serious psychiatric disorder characterised by turbulent interpersonal relationships, impaired self image, impulsivity, and a recurrent pattern of unstable affect which is usually evident by early adulthood. It has a community prevalence rate of two per cent, and approximately nine per cent of people diagnosed with BPD commit suicide. This suggests that BPD has one of the highest lethality rates of all psychiatric disorders. The course of the disorder shows a steady improvement over the course of early adulthood with the majority of cases remitting by middle age. This positive but incomplete long-term recovery is thought to be a naturalistic outcome that is independent of treatment effect. The reported study sought to test selected components of a multidimensional developmental neuropsychological model of executive functioning in BPD. The model proposed that BPD is characterised by impairments to four neuropsychological executive functions. These include working memory, response inhibition, affective-attentional bias, and problem-solving. The model further proposed that impaired executive functioning in BPD occurs as a result of the failure of 'experience-dependent' maturation of orbitofrontal structures. These structures are closely associated with the development of the 'cognitive executive'. The study incorporated a cross-sectional design to analyse data from a BPD group, a Depressed Control Group, and a Medical Control Group. The overall findings of the study returned limited support for the original hypotheses. There was no evidence of deficits in working memory, response-inhibition, or problem-solving. In contrast, the BPD group returned some evidence of deficits in affective-attentional bias. Therefore, the results suggest that executive functioning remains largely intact in BPD. This also suggests that people with BPD have the working memory resources necessary to facilitate abstract cognition, have the capacity to effectively plan and execute future-oriented acts, and are able to perform appropriate problem-solving functions. These problem-solving returns are also particularly significant because a number of the tasks utilised in the study are known to be associated with so-called 'frontal-executive' function. These unremarkable findings challenge the view that people with BPD might experience some form of subtle neurological impairment associated with frontal-lobe compromise. The Stroop measure of affective-attentional bias provided the only supportive evidence for the proposed model, and these findings can be accounted for by at least two different explanations. The first suggests that BPD might be characterised by a hypervigilant attentional set. The specific cause of hypervigilance in BPD is unknown, but some candidate factors appear to be the often-reported abuse histories of borderlines, insecure attachment histories, and deficits in parental bonding. The second interpretation suggests that the Stroop findings reflect a form of 'response conflict' in which BPD participants experience difficulties overriding tasks that rely on the enunciation of automatic neural routines. As a result of these findings, further research on the role of arousal, priming, hypervigilance, and response-conflict in BPD is required. It is likely that the Stroop findings reflect a basic, 'hard-wired' attentional mechanism that consolidates by early adolescence at the latest. As a result, the Stroop findings have implications for both the prevention and treatment of BPD. A number of prevention strategies could be developed to address the attentional issues identified in the present study. These include assisting children to more effectively regulate arousal and affect, and assisting parents to communicate affectively with children in order to enhance self-regulation. The treatment implications suggest that interventions directed at affective-attentional processes are required, and further suggest the need for new pharmacotherapies and psychological treatments to modify dysfunctional attentional process. Affective neuroscience will have an increasingly important role to play in the understanding of BPD, and the next quarter century is likely to witness exciting advances in understanding this most problematic of disorders

Wanda and Joseph: Language development in the context of family stress and trauma

Much has been written on child language development and recent years have seen a burst of research on the psychological and physiological impact of trauma and stress. This study seeks to review existing research on how family trauma influences language development, and consider existing interventions. A case study is presented of work with a mother and her language-­‐delayed child through preventive services. Interventions focused on increasing the mother’s capacity for mentalization and playful interaction with her child were found to be useful in ameliorating communication barriers and increasing the child’s social engagement

Stress estimation by the prefrontal cortex asymmetry: Study on fNIRS signals

sure the brain hemodynamic activity in applications to evaluate affective disorders and stress. Using two wavelengths of light, it is possible to monitor relative changes in the concentrations of oxyhemoglobin and deoxyhemoglobin. Besides, the spatial asymmetry in the prefrontal cortex activity has been correlated with the brain response to stressful situations. Methods: We measured prefrontal cortex activity with a NIRS multi-distance device during a baseline period, under stressful conditions (e.g., social stress), and after a recovery phase. We calculated a laterality index for the contaminated brain signal and for the brain signal where we removed the influence of extracerebral hemodynamic activity by using a short channel. Results: There was a significant right lateralization during stress when using the contaminated signals, consistent with previous investigations, but this significant difference disappeared using the corrected signals. Indeed, exploration of the susceptibility to contamination of the different channels showed non-homogeneous spatial patterns, which would hint at detection of stress from extracerebral activity from the forehead. Limitations: There was no recovery phase between the social and the arithmetic stressor, a cumulative effect was not considered. Conclusions: Extracerebral hemodynamic activity provided insights into the pertinence of short channel corrections in fNIRS studies dealing with emotions. It is important to consider this issue in clinical applications including modern monitoring systems based on fNIRS technique to assess emotional states in affective disorders