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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 -
Neuron Oct 2023The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it...
The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATm) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATm population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATm neurons or multiple downstream pathways. In awake mice, ATm activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.
Topics: Mice; Animals; Arousal; Thalamus; Wakefulness; Neurons; Synaptic Transmission
PubMed: 37557180
DOI: 10.1016/j.neuron.2023.07.007 -
Neuron Feb 2024Ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) drive reward-related motivation. Although dopamine neurons are predominant, a substantial...
Ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) drive reward-related motivation. Although dopamine neurons are predominant, a substantial glutamatergic projection is also present, and a subset of these co-release both dopamine and glutamate. Optogenetic stimulation of VTA glutamate neurons not only supports self-stimulation but can also induce avoidance behavior, even in the same assay. Here, we parsed the selective contribution of glutamate or dopamine co-release from VTA glutamate neurons to reinforcement and avoidance. We expressed channelrhodopsin-2 (ChR2) in mouse VTA glutamate neurons in combination with CRISPR-Cas9 to disrupt either the gene encoding vesicular glutamate transporter 2 (VGLUT2) or tyrosine hydroxylase (Th). Selective disruption of VGLUT2 abolished optogenetic self-stimulation but left real-time place avoidance intact, whereas CRISPR-Cas9 deletion of Th preserved self-stimulation but abolished place avoidance. Our results demonstrate that glutamate release from VTA glutamate neurons is positively reinforcing but that dopamine release from VTA glutamate neurons can induce avoidance behavior.
Topics: Mice; Animals; Glutamic Acid; Dopamine; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Vesicular Glutamate Transport Protein 2; Tyrosine 3-Monooxygenase
PubMed: 38086374
DOI: 10.1016/j.neuron.2023.11.002 -
Nature Feb 2024To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay...
To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOR) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvl) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvl cells minimally respond to aggressor cues. During defeat, aVMHvl cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvl cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.
Topics: Animals; Mice; Aggression; Avoidance Learning; Cues; Fear; Hypothalamus; Neural Pathways; Neurons; Oxytocin; Receptors, Oxytocin; Social Behavior; Social Learning; Supraoptic Nucleus; Ventromedial Hypothalamic Nucleus; Neuronal Plasticity
PubMed: 38267576
DOI: 10.1038/s41586-023-06958-w -
Journal of the American Academy of... May 2024As child psychiatrists, it is our job to ask questions, and many of us would say we are really good at it. We work with our patients to open up about their experiences,...
As child psychiatrists, it is our job to ask questions, and many of us would say we are really good at it. We work with our patients to open up about their experiences, discussing fear, sadness, hope, and joy. By modeling this ability to open up in the office, we help guide children and adolescents through using other skills rather than avoidance. Although avoidance has its place at times, we help show our patients the connection between anxiety and avoidance. This necessity to embrace and challenge fears can be a difficult skill for our patients and also their families. Children bring forward questions that parents may want to avoid, fearing the answer might be more difficult for the child than the rejection of having the question avoided all together. As someone who works with children with chronic illnesses, this avoidance of the question can in fact increase the fear and anxiety of the child or adolescent. When talking to children, often they will express a greater fear than the reality of the situation because they determine that if their parent is avoiding the question, it must be really bad. This same struggle with avoidance can be true for us as child psychiatrists as well. The necessity to take on roles of leadership or run a team often presents itself, but excuses can come up to help us avoid these roles. We might say we are not properly trained, we did not go into medicine to do those responsibilities, or we are too busy. By avoiding these responsibilities, we are setting ourselves up for more frustration. As teams struggle, we have to follow the lead of others without the same clinical knowledge, which may result in additional errors. We must remember to practice what we preach and to identify the cost of avoidance.
Topics: Humans; Child; Adolescent; Child Psychiatry; Fear; Avoidance Learning; Anxiety; Physician-Patient Relations
PubMed: 38387792
DOI: 10.1016/j.jaac.2024.02.004 -
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