Current topics in behavioral neurosciences最新文献

The renin-angiotensin system (RAS) is becoming increasingly recognised as a biochemical pathway relevant to the development and progression of Alzheimer's disease (AD). RAS involvement in AD was initially linked to AD via numerous genetic association studies and more recent Genome-Wide Association Studies (GWAS), and in some cases in relation to classical hallmarks of AD pathology. Since these initial findings, which will be summarised here, several complementary areas of research are converging in support of what has been proposed as the Angiotensin Hypothesis for Alzheimer's disease. This hypothesis proposes how the RAS and disease-associated changes to the normal balance between opposing regulatory pathways within RAS warrant careful consideration in the pathogenesis of AD and its pathology. We discuss some of these in relation to RAS-targeting therapeutics, originally developed for the treatment of cardiovascular conditions, and how they might be repurposed as interventions for AD.

We examine the association between stress exposure during early development (i.e., the prenatal period through the first two postnatal years) and variation in brain structure and function relevant to anxiety. Evidence of stress-related effects occurring in regions essential for emotional processing and regulation may increase susceptibility to anxiety.

The mind is embodied, and this is relevant to mental health and psychiatric illness. Interoception is the body-to-brain axis of sensory information flow and its representation at the neural and psychological levels. Interoception is the purported basis for motivation and emotion, and as an inescapable stream of information about the health and functioning of the whole organism, it is proposed to be the foundation to the conscious unitary sense of self. Correspondingly, this central representation of internal state is relevant to understanding the expression of psychological symptoms and behaviours and ultimately psychiatric disorders. Here we review interoception, particularly from a cardiovascular perspective, and how understanding theoretical neural and psychological aspects of interoception relates to perceptions, thoughts, and feelings. We examine how perturbations in interoceptive processing are expressed in mental symptoms and psychiatric disorders and show how this knowledge may yield new treatment targets.

Although women are diagnosed with anxiety and stress-related disorders at twice the rate of men, there remains a lack of clarity around how to enhance treatment within each sex to reduce disparate rates of anxiety. However, in recent years, a growing literature has identified neural, cognitive, and physiological mechanisms that contribute to sex differences in fear and anxiety, with the promise of informing tailored treatment approaches. Here, we review recent findings, focusing on human studies among healthy populations as well as among patients with generalized anxiety, social anxiety disorder, post-traumatic stress disorder, and panic disorder. The literature reveals nuanced differences in the types of stimuli that preferentially evoke anxiety and stress responses in women and men, as well as sex differences in threat neurocircuitry that mediates the behavioral, physiological, and subjective components of fear and anxiety.

Anxiety and related disorders are prevalent across the lifespan, often have their onset during youth, and are associated with notable levels of impairment and burden across multiple domains. Elucidating the associations between differential patterns of neurodevelopment and anxiety in youth is a promising approach for developing deeper insights regarding the neurobiological etiologies and maintenance factors associated with anxiety and related disorders. A growing body of literature has yielded evidence of associations between patterns of brain structure (i.e., volume, cortical thickness, and cortical surface area) and anxiety. Here, we present a review and synthesis of the existing body of literature surrounding neurostructural correlates of anxiety in youth spanning multiple anxiety presentations and three neurostructural modalities. We reveal substantially more research focusing on brain volume than cortical thickness or surface area and a greater number of studies examining anxiety broadly defined, obsessive-compulsive disorder, or posttraumatic stress disorder. There is also evidence of considerable variability in the brain regions implicated and the direction of associations across studies. Finally, we discuss the gaps and limitations in this body of work, which suggest avenues for future directions.

Down syndrome (DS) is the most frequent cause of intellectual disability of genetic origin, estimated to affect about 1 in 700 babies born worldwide (CDC 2023). In Europe and the United States, current estimates indicate a population prevalence of 5.6 and 6.7 per 10,000 individuals, respectively, which translates to more than 200,000 people in the United States, more than 400,000 people in Europe, and approximately six million worldwide. Advances in healthcare and the treatment of accompanying conditions have significantly prolonged the lifespan of those with DS over the past 50 years. Consequently, there is a pressing need to address the challenges associated with ageing among this population, with Alzheimer's disease (AD) being the primary concern. In this chapter, we will review the significance of studying this population to understand AD biology, the insights gained on AD in DS (DSAD), and how this knowledge can help us understand the AD not only in DS but also in the general population. We will conclude by exploring the objectives that remain to be accomplished.

In this chapter, we provide an overview of ethical aspects of psychedelic-assisted treatments in the areas of clinical ethics, research ethics, and at the intersection of psychedelic medicine and society. In contrast to earlier psychedelic research, nowadays medical ethics have been firmly established as a discipline regulating patient-physician relationships which highlight the importance of autonomy, shared decision-making and informed consent in clinical ethics. During and after altered states of consciousness, autonomy is particularly important as participants are in a vulnerable state. In this vulnerable state, both touch and suggestibility are central ethical concerns. In turn, the debate surrounding hallucinogenic and nonhallucinogenic psychedelic substances discusses the importance of altered states of consciousness in general. Of further concern are exceptional training requirements and competencies of psychedelic therapists, as well as the particular context of end-of-life care. Lastly, this section discusses how ethical integrity in clinical treatments can be supported through institutions. In research ethics, inclusivity, research equipoise, and expectation management are key issues in the participation and trials, while open question for the posttrial access to care after psychedelic trials remain. Finally, the chapter addresses the question of equitable access to psychedelic medicine. Furthermore, justice for indigenous communities using psychedelics and the impact of legalization and medicalization of psychedelic substances are pressing ethical concerns amidst the "psychedelic renaissance."

Posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD) are debilitating psychiatric disorders. While treatments are often effective, many patients do not adequately respond or experience significant side effects. Transcranial magnetic stimulation (TMS) is an emerging approach for treating PTSD and GAD. Several randomized clinical trials have demonstrated that TMS over the dorsolateral prefrontal cortex may be efficacious in reducing psychiatric symptoms; however, results are inconsistent regarding whether any parameter or treatment paradigm is superior. Other RCTs have targeted novel brain regions using newer TMS modalities. Combining TMS with psychotherapy may augment response in patients with PTSD, yet results are inconclusive. Little research has been done on TMS in combination with psychotherapy for GAD, indicating a need for further investigation. Future studies may assess TMS parameter optimization for enhancing effectiveness and improving therapeutic response duration. Identifying response biomarkers through functional magnetic resonance imaging and electroencephalography may offer a means to predict and monitor clinical response as precision methods to improve treatment response.

The functional complexity of brain circuits underlies the broad spectrum of behaviors, cognitive functions, and their associated disorders. Mitochondria, traditionally known for their role in cellular energy metabolism, are increasingly recognized as central to brain function and behavior. This review examines how mitochondria are pivotal in linking cellular energy processes with the functioning of neural circuits that govern fear and anxiety. Following an introductory section in which we summarize current knowledge about fear and anxiety neural circuits, we provide a brief summary of mitochondria fundamental roles (e.g., from energy production and calcium buffering to their involvement in reactive oxygen species (ROS) generation, mitochondrial dynamics, and signaling), particularly emphasizing their contribution to synaptic plasticity, neurodevelopment, and stress response mechanisms. The review's core focuses on the current state of knowledge regarding how mitochondrial function and dysfunction impact the neural substrates of fear and anxiety. Furthermore, we explore the implications of mitochondrial alterations in the context of posttraumatic stress disorder (PTSD) and anxiety disorders, underscoring the potential of mitochondrial pathways as new therapeutic targets. Integrating insights from genetic, biochemical, neurobiological, behavioral, and clinical studies, we propose a model in which mitochondrial function is critical for regulating the neural circuits that underpin fear and anxiety behaviors, highlighting how mitochondrial dysfunction can lead to their pathological manifestations. This integration emphasizes the potential for developing novel treatments targeting the biological roots of fear, anxiety, and related disorders. By merging mitochondrial biology with behavioral and circuit neuroscience, we enrich our neurobiological understanding of fear and anxiety, uncovering promising avenues for therapeutic intervention.

Belief change is crucial to therapeutic benefit in psychedelic-assisted therapy as well as in more traditional forms of therapy. However, the use of psychedelics comes with a few unique challenges that require extra caution. First, drastic belief changes may occur faster than in regular therapy. Facing radical and transformative insights all at once rather than through a gradual process of discovery and integration can lead patients to a volatile, confusing or disorienting epistemic state. Additionally, we know psychedelic substances generate hallucinatory experiences that come with a high degree of confidence and noetic certainty despite not necessarily being connected with reality. On the other hand, telling a patient which ones of her beliefs are true and which ones are not seems beyond the competence of a psychotherapist, if not an abuse of their authority and power. This is even more dangerous when psychedelics are involved, because power imbalance between patient and therapist is exacerbated by the therapist's role as a guiding figure throughout an intense altered state of consciousness. Because of this suggestible state, the therapist's beliefs might have a disproportionate influence, and even well-intentioned nudging might significantly stray the patient's beliefs.How can a therapist help a patient navigate their epistemic uncertainty around psychedelic insights while preserving the patient's autonomy? This chapter will attempt to answer this question through a philosophical and epistemological lens. We will review different strategies to mitigate epistemic risks in psychedelic-assisted therapy and argue that such risks can be significantly reduced by adapting these strategies dynamically to the individual patient's needs.