Delirium is a typical acute stage of organic psychiatric disease while dementia is a chronic and irreversible pathology. It has long been pointed out that neuroinflammation plays an important role in neurodegenerative diseases such as Alzheimer’s disease, but neuroinflammation has recently been reported to play an important role in a wide range of psychiatric disorders such as schizophrenia and mood disorders. It is easy to imagine from the pathology of delirium that neuroinflammation plays a greater role in the pathophysiology of delirium than in schizophrenia or mood disorders. In this article, we reviewed the literatures regarding the neuroinflammatory hypothesis of delirium.

Oxidative stress is a state in which excessive production of antioxidants impairs the balance between oxidants and antioxidant defense systems. Oxygen is essential for humans to sustain life activities, and a few percent of oxygen taken in by living bodies is believed to turn into reactive oxygen species (ROS). ROS is mainly produced in mitochondria inside the cells and functions as a physiologically active substance in cell signaling, differentiation, death, and immunity. If ROS becomes excessive for some reason and exceeds the antioxidant defense mechanism, it would cause cell damage which leads to various diseases. Elderly people are vulnerable to diseases due to accumulation of tissue/cell damage by oxidative stress and due to waned antioxidant defense systems. Moreover, the central nervous system, which is abundant with lipids in the myelin sheath, is assumed to have weaker antioxidant defense mechanisms than other organs, and various pathologies are likely to be induced by ROS. Delirium is an example of such a pathology. ROS overproduction in the brain due to infection or disruptions in metabolism and circulation can damage cell organelles, nucleic acids, enzymes, and signaling molecules. ROS, oxidants, and damage-associated molecular patterns (DAMPs) activate microglia which is an immune cell in the brain. Activated microglia produces ROS and cytokines, damaging brain cells including astrocytes in the blood-brain barrier. The damage leads to increased permeability of the blood-brain barrier, which allows pathological or inflammatory substances to enter the brain. Oxidative stress may contribute to the development of delirium through these mechanisms. ROS might cause irreversible cell damage and neurodegeneration. Recent reports have highlighted several strategies aimed at reducing oxidative stress in the central nervous system as a means of treating neurodegenerative diseases. Antioxidants have been proposed as a potential means to prevent delirium and cognitive decline following delirium, despite their inability to alleviate acute symptoms. Additional investigation is warranted.

The underlying pathophysiology of delirium remains unclear, with several pathophysiological hypotheses having been proposed. This article outlines the current state of knowledge regarding the neuroendocrine hypothesis, which is at the core of the pathophysiology of delirium. It has been postulated that the negative feedback function of the Hypothalamus-Pituitary-Adrenal gland axis (HPA axis) is impaired in delirium. The physiological stress response of the body to emotional, chemical, and physical stress is the facilitation of glucocorticoid (GC) secretion through the HPA axis, which maintains the homeostasis through the anti-inflammatory effects of the secreted GCs. Stress is first sensed by the amygdala and hippocampus, with the amygdala facilitating the HPA system and the hippocampus inhibiting it. Furthermore, secreted GCs facilitate the amygdala and inhibit the hippocampus. Therefore, chronic and excessive emotional stress results in the overactivation of the amygdala, which is the center for emotional memory. This overactivation leads to the oversecretion of GCs, which creates a positive feedback loop promoting further amygdala overactivity. In addition, chronic and high levels of GC secretion can be reversed as increasing the expression of proinflammatory cytokines, which in turn enhances immune function. This results in neuronal damage. These findings may explain the mechanism of the impaired negative feedback function of the HPA axis in delirium. Since stress-responsive neuroendocrine mechanisms are assumed to play an important role not only in delirium but also in various psychiatric disorders, studies using delirium as a model may provide fundamental knowledge for the development of neuropsychiatric disorders treatment.

Objectives: This study aimed to clarify the characteristics of the psychiatric departments of Special Functioning Hospitals (SFHs), which have psychiatric beds. Methods: The numbers of psychiatric beds and psychiatrists, and their ratio to per capita and geographical distributions were extracted based on a review of annual business reports submitted to the Ministry of Health, Labour and Welfare in 2018 from 75 SFHs. Moreover, the scope of clinical practice including targeted patients, diseases, and treatments were extracted and analyzed inductively through text-mining of the departments’ websites. Results: The number of psychiatric beds in the 75 SFHs constituted about 1% of all psychiatric beds in Japan, and many of these SFHs were established by public institutions. There were diverse and wide-ranging treatment targets and methods of clinical practice, which included treatment of patients with physical complications and aspects of multi-departmental and institutional collaboration, including consultation-liaison psychiatry services. Conclusions: The SFHs have a wide range of medical targets, treatment methods, and collaborations with other institutions.

GABA-BZ receptor agonists have anxiolytic, sedative, and hypnotic effects. However, various adverse events such as cognitive decline, falls and addiction formation due to high dose and long-term use have been reported. Therefore, lemborexant (hereinafter referred to as LEM), which is an orexin receptor antagonist, is expected as a new hypnotic. In this study, patients who changed from long-term oral GABA-BZ receptor agonists to LEM were classified into a weight reduction group at the time of LEM introduction and a weight reduction group after LEM introduction. A comparative study was conducted up to 12 weeks after switching. Of the cases of oral administration of GABA-BZ receptor agonist, 40 cases were changed to LEM, and 33 cases were subjects. There was no significant difference in the switching success rate between the two groups, but a switching success rate of about 80% was observed in both groups. In addition, no serious side effects occurred. Therefore, LEM may be expected as a replacement drug for patients taking GABA-BZ receptor agonists for a long time, suggesting that it may be useful as an option.

In recent years, mental disorders in cancer patients have become an important theme of general hospital psychiatry. In particular, breast cancer presents with mental disorders due to long-term treatment periods and/or the reaction of hormonal therapy. We report a case of postoperative mood disorder after breast cancer diagnosis that lasted several years and obtained consent to describe the course of treatment including life events during that period. In this case report, we summarized the changes in mood and drug therapy over time, and considered the psychological impacts of life events, including loss due to the death of the patient’s father, which was also from cancer, and separation because of the marriage of patient’s son. During the psychotherapy process some interesting dreams were reported. Through these processes we considered the significance of psychotherapy in the field of palliative care. In this case, the patient’s mood disorder was a real-life illness. However, spiritually, it was evaluated as a process of suffering as the patient was raised by a protective father, became an independent being, and then witnessed the death of her father. For cancer patients who realize that death is inevitable, it is important for them to review their lives and look for significance. The purpose of psychotherapy in the field of palliative care is to provide support that brings the patient’s individual life closer to the patient’s own life. Therefore, it is necessary for therapists to be aware of their own mortality.