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Zeitschrift Fur Kinder- Und... Jul 2023Pathological Demand Avoidance: Current State of Research and Critical Discussion Pathological demand avoidance (PDA) describes children who obsessively avoid any demand... (Review)
Review
Pathological Demand Avoidance: Current State of Research and Critical Discussion Pathological demand avoidance (PDA) describes children who obsessively avoid any demand to a clinically relevant extent and is presently the subject of controversial discussion. Their behavior may be interpreted as an attempt to reduce anxiety by establishing security and predictability through rigid control of the environment as well as the demands and expectations of others. The symptoms are described in the context of autism spectrum disorder. This article reviews the current state of research and discusses the questionable validity of pathological demand avoidance as an independent diagnostic entity. It also addresses the impact of the behavior profile on development and treatment. This paper concludes that PDA is not a diagnostic entity nor a subtype of autism; rather, it is a behavior profile that can be associated with adverse illness progression and unfavorable outcomes. PDA is one feature in a complex model. We must consider not only the patient's characteristics but also those of the caregiver and their psychopathology. The reactions of the interaction partners as well as the treatment decisions play a key role play for the affected individuals. Substantial research is needed concerning the occurrence of the behavior profile PDA in diverse disorders, treatment options, and treatment responses.
Topics: Child; Humans; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Child Behavior Disorders; Anxiety; Autistic Disorder
PubMed: 36892327
DOI: 10.1024/1422-4917/a000927 -
Nature Aug 2023In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour. The scope and mechanisms of behavioural modifications by...
In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.
Topics: Animals; Mice; Allergens; Avoidance Learning; Central Amygdaloid Nucleus; Disease Models, Animal; Food Hypersensitivity; Immunoglobulin E; Intestines; Mast Cells; Mice, Inbred BALB C; Mice, Inbred C57BL; Parabrachial Nucleus; Solitary Nucleus
PubMed: 37437602
DOI: 10.1038/s41586-023-06362-4 -
Nature Aug 2023The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with...
The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance. Here, we show that antigen-specific avoidance behaviour in inbred mice is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.
Topics: Animals; Mice; Allergens; Avoidance Learning; Hypersensitivity; Immunoglobulin E; Mast Cells; Stomach; Vagotomy; Immunity, Innate; Immunity, Mucosal; Th2 Cells; Cytokines; Leukotrienes; Intestine, Small
PubMed: 37438525
DOI: 10.1038/s41586-023-06188-0 -
Cureus Aug 2023Autism spectrum disorder (ASD) is a neurodevelopmental condition made up of enduring challenges in social communication and interaction and the presence of repetitive... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental condition made up of enduring challenges in social communication and interaction and the presence of repetitive and restricted behavior patterns. Early diagnosis of autism is crucial for timely intervention and improved long-term outcomes. This review aims to explore some of its signs and symptoms, look into some diagnostic tools, and analyze the benefits and risks associated with an early diagnosis of autism. The symptoms of ASD vary from child to child, some of which are: avoidance of eye contact, lack of response to names, excessive fear, and lack of interactive and pretend play. Early identification of these symptoms by caregivers and healthcare providers facilitates the need for diagnosis and appropriate interventions. Some screening and diagnostic tools that have been found to help make the diagnosis are the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F), the Social Communication Questionnaire (SCQ), the Parents' Evaluation of Developmental Status (PEDS), and the Childhood Autism Rating Scale (CARS), amongst others. The benefits of early diagnosis include the opportunity for early intervention, which has been shown to enhance developmental outcomes and improve adaptive skills. Early identification allows for the implementation of specialized interventions tailored to the specific needs of individuals with autism, targeting social communication, language development, and behavioral challenges. Furthermore, early diagnosis enables families to access appropriate support services, educational resources, and community programs, facilitating better coping mechanisms, reducing parental stress, and increasing adult independence. However, early diagnosis of autism also entails certain risks. One significant concern is the potential for labeling and stigmatization, which can impact the child's self-esteem and social interactions. There is a risk of overdiagnosis or misdiagnosis, leading to unnecessary interventions and treatments. Additionally, the diagnostic process can be lengthy, complex, and emotionally challenging for families, requiring comprehensive assessments by multidisciplinary teams. This review highlights the importance of a balanced approach when considering the benefits and risks of early diagnosis. Early identification allows for timely interventions that significantly improve developmental outcomes and quality of life for individuals with autism. To mitigate the risks, it is crucial to ensure accurate and reliable diagnostic procedures, support families throughout the process, and promote societal awareness and acceptance. We also highlighted some future directions in the management of autism, including the use of biomarkers and the use of artificial intelligence and learning for diagnosing ASD.
PubMed: 37692637
DOI: 10.7759/cureus.43226 -
Neurobiology of Learning and Memory Oct 2023Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative... (Review)
Review
Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative learning depending on type, intensity, and persistence of the stressor, the subject's sex, the context that the stress and behavior is experienced in, and the type of associative learning taking place. In some cases, stress can cause or exacerbate the maladaptive behavior that underlies numerous psychiatric conditions including anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, substance use disorder, and others. Therefore, it is critical to understand how the varied effects of stress, which may normally facilitate adaptive behavior, can also become maladaptive and even harmful. In this review, we highlight several findings of associative learning and decision-making processes that are affected by stress in both human and non-human subjects and how they are related to one another. An emerging theme from this work is that stress biases behavior towards less flexible strategies that may reflect a cautious insensitivity to changing contingencies. We consider how this inflexibility has been observed in different associative learning procedures and suggest that a goal for the field should be to clarify how factors such as sex and previous experience influence this inflexibility.
Topics: Humans; Adaptation, Psychological; Anxiety Disorders; Conditioning, Classical; Stress Disorders, Post-Traumatic
PubMed: 37598745
DOI: 10.1016/j.nlm.2023.107812 -
Proceedings of the National Academy of... Dec 2023Clinical studies have revealed a high comorbidity between autoimmune diseases and psychiatric disorders, including major depressive disorder (MDD). However, the...
Clinical studies have revealed a high comorbidity between autoimmune diseases and psychiatric disorders, including major depressive disorder (MDD). However, the mechanisms connecting autoimmunity and depression remain unclear. Here, we aim to identify the processes by which stress impacts the adaptive immune system and the implications of such responses to depression. To examine this relationship, we analyzed antibody responses and autoimmunity in the chronic social defeat stress (CSDS) model in mice, and in clinical samples from patients with MDD. We show that socially stressed mice have elevated serum antibody concentrations. We also confirm that social stress leads to the expansion of specific T and B cell populations within the cervical lymph nodes, where brain-derived antigens are preferentially delivered. Sera from stress-susceptible (SUS) mice exhibited high reactivity against brain tissue, and brain-reactive immunoglobulin G (IgG) antibody levels positively correlated with social avoidance behavior. IgG antibody concentrations in the brain were significantly higher in SUS mice than in unstressed mice, and positively correlated with social avoidance. Similarly, in humans, increased peripheral levels of brain-reactive IgG antibodies were associated with increased anhedonia. In vivo assessment of IgG antibodies showed they largely accumulate around blood vessels in the brain only in SUS mice. B cell-depleted mice exhibited stress resilience following CSDS, confirming the contribution of antibody-producing cells to social avoidance behavior. This study provides mechanistic insights connecting stress-induced autoimmune reactions against the brain and stress susceptibility. Therapeutic strategies targeting autoimmune responses might aid in the treatment of patients with MDD featuring immune abnormalities.
Topics: Humans; Mice; Animals; Autoimmunity; Depressive Disorder, Major; Brain; Social Behavior; Immunoglobulin G; Stress, Psychological; Mice, Inbred C57BL
PubMed: 38011565
DOI: 10.1073/pnas.2305778120 -
The Neuroscientist : a Review Journal... Aug 2023Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been... (Review)
Review
Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been extensively used in animal research to better understand how changes in neural activity within the prefrontal cortex contribute to avoidance behaviors, which are believed to play a major role in the maintenance of anxiety disorders. In this article, we first review studies utilizing electrophysiology to reveal the relationship between changes in neural activity and avoidance behavior in rodents. We then review recent studies that take advantage of optical and genetic techniques to test the unique contribution of specific prefrontal cortex circuits and cell types to the control of anxiety-related avoidance behaviors. This new body of work reveals that behavior during approach-avoidance conflict is dynamically modulated by individual cell types, distinct neural pathways, and specific oscillatory frequencies. The integration of these different pathways, particularly as mediated by interactions between excitatory and inhibitory neurons, represents an exciting opportunity for the future of understanding anxiety.
Topics: Animals; Anxiety; Anxiety Disorders; Prefrontal Cortex; Avoidance Learning; Neural Pathways
PubMed: 35086369
DOI: 10.1177/10738584211069071