CNS Spectrums最新文献

This article presents a comprehensive neuroethical framework that seeks to deepen our understanding of human consciousness and free will, particularly in the context of psychiatric and neurological disorders. By integrating insights from neuroscience with philosophical reflections on freedom and personal identity, the paper examines how various states of consciousness from interoception to self-awareness influence an individual's autonomy and decision-making capabilities. The discussion utilizes a multidimensional, bottom-up approach to explore how neurobiological processes underlie different levels of conscious experience and their corresponding types of freedom, such as "intero-freedom" related to internal bodily states and "self-freedom" associated with higher self-awareness. This stratification reveals the profound impact of neurological conditions on patients' freedom of choice and the ethical implications therein. The insights gained from this analysis aim to inform more tailored and effective treatments for psychiatric patients, emphasizing the restoration of autonomy and respect for their inherent dignity. This work underscores the essential unity of the human person through the lens of neuroethics, advocating for healthcare policies that recognize and enhance the personal freedom of those with mental health challenges.

Schizophrenia is a highly heterogenous disorder with substantial interindividual variation in how the illness is experienced and how it presents clinically. The disorder is composed of primary symptom clusters-positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. These, along with duration, severity, and excluding other possible etiologies, comprise the diagnostic criteria for the disorder outlined in the two commonly used diagnostic classification systems-the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition, Text Revision and the International Classification of Diseases, 11^th Revision. These primary symptoms as well as accessory symptoms (mood disturbances, anxiety, violence) and comorbidities (substance use, suicidality) bear upon each other to varying degrees and impact functional outcomes. The following review presents two patient cases illustrating the clinical heterogeneity of schizophrenia, the natural history of the illness and diagnosis, followed by the current understanding of the primary symptom clusters, accessory symptoms, and comorbidities. In addition to noting symptom prevalence, onset, and change over time, attention is paid to the impact of symptoms on functional outcome.

This article, titled "A Unified Understanding of the Human Mind - A Neuroethical Perspective," examines the evolution of the concept of the human mind in Western thought and its integration with neuroscience, psychology, psychiatry, and relational dimensions. The author explores how the understanding of the mind has changed over time, influenced by shifts in philosophical paradigms, scientific advancements, and societal perspectives. The article traces the historical development of the mind's concept, starting from ancient Greece, through influential thinkers like Plato and René Descartes, and progressing to contemporary perspectives. It highlights various philosophical and scientific approaches, including structuralism, functionalism, empiricism, and associationism, which have shaped our understanding of the mind. The article also delves into contemporary integration, where advancements in neuroimaging and the rise of holistic approaches offer a more nuanced understanding of the human mind. The author emphasizes the importance of the relational dimension and the interconnectedness of mental processes, the brain, and the external environment. This integrated perspective can benefit psychiatric treatment and psychological assessments by fostering a holistic approach to mental health. In conclusion, the article advocates for a multidimensional perspective that bridges subjective and objective aspects of human experience, offering promise for theoretical knowledge and practical applications in psychology, psychiatry, and neuroscience.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanism of postsynaptic dopamine D₂ receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine's superiority to risperidone for negative symptoms. The muscarinic M₁/M₄ agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks any D₂ receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinic M₁ receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.

The CDC reports that the United States has the highest suicide rates in over 80 years. Numerous public policies aimed at reducing the rising suicide rates, such as Aetna's partnership with the American Foundation for Suicide Prevention (AFSP) and the zero-suicide initiative, continue to challenge these attempts. It, therefore, remains imperative to explore the shortcomings of these efforts that hamper their efficiency in reducing suicide rates. Advancements in research over time have sparked scientific skepticism, encouraging re-evaluation of established concepts. The current paper tests prevalent assumptions and arguments to uncover a scientifically informed approach to addressing rising suicide rates in clinical settings.