Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression

The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The MPFC is part of a larger “default system” of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions. Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans. Further, because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders. This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies

The impact of early-life stress in the development and course of bipolar disorder: Mechanisms and implications

Traumatic events experienced throughout the different stages of childhood and adolescence are frequent circumstances with a detrimental impact on the physical and psychological health of the individual. A growing body of evidence shows the trauma-related effects on the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system, the serotonin system, the immune system, on brain development, structure, and connectivity. Interestingly, a relation was found between early life stress and Bipolar Disorder: the patients who were exposed to childhood trauma showed a worsened course of the disorder with poor clinical and psychopathological factors. According to the kindling hypothesis, early environmental stressors interact with the genetic susceptibility through epigenetic mechanisms, making the subject more vulnerable to milder stressors, and lowering the threshold for the occurrence of subsequent mood episodes. Understanding these processes is crucial to the discovery of new targets of treatment to reduce or, possibly, revert the effect of early life stress on bipolar disorder

Hallucinogens: mechanisms and medical complications

Thesis (M.A.)--Boston UniversityHallucinogens are drugs that alter consciousness by distorting primarily auditory and visual perception but they can affect any sensory system. Hallucinogens also affect judgment, orientation, memory, or emotion. Despite the profound alteration in perception, adverse effects are minimal and hallucinogens are not addictive. Hallucinogen use has its roots in shamanic practices of indigenous cultures and is even incorporated in today’s religions like the Native American Church. By putting a person in an altered state of consciousness, many religions believed that the user was able to see beyond the boundaries of reality and reach out to mythical beings. Hallucinogen use in scientific research was not popular until the 1950’s when Albert Hoffman discovered lysergic acid diethylamide (LSD). The discovery of drug encouraged further research into understanding its mechanisms and its relationship with mental diseases like schizophrenia. Unfortunately, the Comprehensive Drug Abuse Prevention and Control Act of 1970 significantly limited hallucinogenic research and human research for the last 42 years. However, animal research in the last 20 years has determined the importance of serotonergic mechanisms and more specifically the 5-HT2A receptors in mediating LSD’s hallucinogenic effects. Researchers continue to identify mechanisms of LSD action. In addition to serotonergic actions, LSD is active with dopaminergic and metabotropic glutamate receptors. PET scans and fMRI’s have also revealed the importance of the prefrontal cortical region and its interaction with other areas during a hallucinogenic state. The relationship between LSD and acute psychosis is also being explored via animal models. Although human clinical research is limited, recent research sees a much deeper relationship by linking LSD brain activity and neurotransmitter levels to psychotic behaviors. This further understanding of hallucinogens on a physiological and psychological level has led to possible psychotherapeutic areas of research in anxiety and substance abuse. This thesis describes a brief history of hallucinogenic research, the pharmacology and neuroanatomy of serotonergic hallucinogens, the acute and chronic adverse effects of serotonergic hallucinogens, the possible treatments for complications of hallucinogens, the epidemiology, the relationship between hallucinogens and schizophrenia, and possible therapeutic uses of serotonergic hallucinogens. With its minimal adverse effects in humans and its powerful influence on the human psyche, serotonergic hallucinogens are invaluable tools for understanding the human mind

What does immunology have to do with brain development and neuropsychiatric disorders?

Introdução: O desenvolvimento neural é um processo extremamente complexo e dinâmico. Tao pronto se inicia o desenvolvimento do cérebro, as "células imunológicas" desempenham um papel fundamental em vários processos, incluindo a formação e aperfeiçoamento de circuitos neurais, bem como a diferenciação sexual. Há um crescente corpo de evidências de que o sistema imunológico também desempenha um papel importante na fidiopatologia de diversos transtornos neurodesenvolvimentais e neuropsiquiátricos. Objetivo: O objetivo deste artigo é revisar os dados atualmente disponíveis sobre o papel do "sistema imunológico" em relação ao desenvolvimento normal do cérebro, bem como a fisiopatogenia dos transtornos de neurodesenvolvimento e neuropsiquiátricos. Metodologia: Foi realizada uma pesquisa bibliográfica tradicional para localizar artigos de revisão relevantes. Resultados: Os processos celulares e moleculares que compõem o nosso "sistema imunológico" são cruciais para o desenvolvimento normal do cérebro e a formação e manutenção de circuitos neurais. É cada vez mais evidente que o sistema imunológico e neuroinflamação desempenham papéis importantes na etiopatogenia de pelo menos um subconjunto de indivíduos com autismo, esquizofrenia, transtorno obsessivo-compulsivo, síndrome de Tourette, depressão e transtornos do humor, bem como distúrbios autoimunes e neurodegenerativos. Evidências emergentes também apontam para a importância do eixo intestino-cerebral e do microbioma de um indivíduo em relação à sua saúde e bem-estar somático e mental. Conclusões: Existem interconexões multidirecionais entre múltiplos sistemas biológicos em nossos cérebros e corpos que são mediados em parte pelo sistema imunológico. No momento, no entanto, a "promessa" desse campo continua sendo maior do que os "resultados finais". O tempo dirá se novas intervenções serão desenvolvidas que farão uma diferença positiva no cuidado de nossos pacientes. Também é possível que surjam biomarcadores válidos que orientarão uma abordagem mais personalizada ao tratamento.Introduction: Neural development is an enormously complex and dynamic process. From very early in brain development ‘immune cells’ play a key role in a number of processes including the formation and refinement of neural circuits, as well as sexual differentiation. There is a growing body of evidence that the immune system also plays an important role in the pathobiology of several neurodevelopmental and neuropsychiatric disorders. Objective: The goal of this article is to review the currently available data concerning the role of the ‘immune system’ in normal brain development, as well as its role in the pathobiology of neurodevelopmental and neuropsychiatric disorders. Methodology: We conducted a traditional literature search using PubMed and recent special issues of journals to locate relevant review articles. Results: The cellular and molecular processes that make up our ‘immune system’ are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that the immune system and neuroinflammation play important roles in the pathobiology of at least a subset of individuals with Autism Spectrum Disorder (ASD), schizophrenia, obsessive-compulsive disorder, Tourette syndrome and mood disorders, such as depression, as well as autoimmune and neurodegenerative disorders. Emerging evidence also points to the importance of the ‘gut-brain axis’ and an individual’s microbiome, which can impact an individual’s somatic and mental well-being. Conclusions: There are multidirectional interconnections across multiple biological systems in our brains and bodies that are mediated in part by the immune system. At present, however, the ‘promise’ of this field remains greater than the ‘deliverables.’ Time will tell whether novel interventions will be developed that will make a positive difference in the care of our patients. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to treatment

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

Brain entropy, fractal dimensions and predictability: a review of complexity measures for EEG in healthy and neuropsychiatric populations

There has been an increasing trend towards the use of complexity analysis in quantifying neural activity measured by electroencephalography (EEG) signals. On top of revealing complex neuronal processes of the brain that may not be possible with linear approaches, EEG complexity measures have also demonstrated their potential as biomarkers of psychopathology such as depression and schizophrenia. Unfortunately, the opacity of algorithms and descriptions originating from mathematical concepts have made it difficult to understand what complexity is and how to draw consistent conclusions when applied within psychology and neuropsychiatry research. In this review, we provide an overview and entry-level explanation of existing EEG complexity measures, which can be broadly categorized as measures of predictability and regularity. We then synthesize complexity findings across different areas of psychological science, namely, in consciousness research, mood and anxiety disorders, schizophrenia, neurodevelopmental and neurodegenerative disorders, as well as changes across the lifespan, while addressing some theoretical and methodological issues underlying the discrepancies in the data. Finally, we present important considerations when choosing and interpreting these metrics

Clinical correlates of emotional dysregulation in bipolar disorder spectrum: a case-control study

openL'attuale studio si propone di studiare e quantificare le differenze tra i pazienti con BD, quelli con BPD, e controlli sani in (a) disregolazione emotiva utilizzando Difficoltà nelle scale di disregolazione delle emozioni (DERS), (b) impulsività valutata da Barratt Inibiion Scale (BIS-11), (c) abusi della prima infanzia utilizzando il Child Trauma Questionnaire (CTQ) e (d) funzionamento quotidiano con il World Health Organization Disability Assessment Schedule (WHODAS.2). Questo studio si propone di aiutare i medici nel compito impegnativo di distinguere tra i pazienti con BD e BPD, contribuendo così al perfezionamento della diagnosi precoce di questi disturbi.The current study aims to investigate and quantify differences between patients with BD, those with BPD, and healthy controls in (a) emotional dysregulation using Difficulties in emotion dysregulation scales (DERS), (b) impulsivity assessed by Barratt Inhibition Scale (BIS-11), (c) early childhood abuses using the Child Trauma Questionnaire (CTQ) and (d) daily functioning with the World Health Organization Disability Assessment Schedule (WHODAS.2). This study aims to assist clinicians in the challenging task of distinguishing between patients with BD and BPD, thereby contributing to the refinement of the earlier diagnosis of these disorders

TITE: ESTABLISHING AN INTEGRATED DIAGNOSTIC PROFILE OF AUTISM SPECTRUM DISORDER (ASD) THROUGH THE USE OF ESSENCE FRAMEWORK. THE CASE STUDY OF A 3-YEAR-OLD INFANT

Neurodevelopmental disorders appear in early childhood and cause serious impairment in several areas. These are characterized by damages or delays in development of functions closely associated with the biological aging of the central nervous system. Neurodevelopmental disorders include speech and language disorders, learning disorders, motor and divisive disorders such as Autism Spectrum Disorder (ASD). Aiming to explore the various phenotypic characteristics of these disorders as well as their co-morbidity or coexistence, an emerging body of studies stressed the importance of both early multidisciplinary assessment and intervention in the framework of these disorders. Due to the complexity of neurodevelopmental disorders there should be specific diagnostic groups so as to apply timely and multifactorial diagnoses. Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE) are considered as an assessment concept that could contribute to multifactorial early diagnosis of neurodevelopmental disorders. Early, adequate, and comprehensive diagnosis conduces to early, effective, and well adapted to individual’s needs intervention programs. In the current study, the ESSENCE framework was used as the key diagnostic approach for both definitive and multifactorial diagnosis of a 3-year-old infant with a wide range of impairments.   Article visualizations