Association of COVID-19 preventive behavior and job-related stress with the sleep quality of healthcare workers one year into the COVID-19 outbreak: a Japanese cross-sectional survey.

BACKGROUND: This study aimed to evaluate the association of COVID-19 preventive behavior and job-related stress with sleep quality among healthcare workers (HCWs). We conducted a cross-sectional survey using a questionnaire at the National Center of Neurology and Psychiatry, Tokyo, Japan. METHODS: A total of 586 participants who completed the questionnaire were eligible for the study. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality. We examined the level of engagement between poor sleep and COVID-19-related infection preventive behaviors, such as avoiding closed spaces, crowded places, and close contact (three Cs), a distance of at least one meter from others, wearing a face mask regularly, washing hands regularly, and working remotely, as well as job-related stress in the work environment, exposure to patients, potential risk of infection, fear of infecting others, need for social confinement, and financial instability. We conducted a hierarchical logistic regression analysis to examine the relationship between poor sleep and COVID-19 preventive behavior, job-related stress, and other covariates, including age, sex, and the Kessler Psychological Distress Scale (K6), which was used to measure non-specific psychological distress. RESULTS: Poor sleep was observed in 223 (38.1%) participants. Adherence to COVID-19 preventive measures was relatively high: 84.1% of participants answered "always" for wearing a face mask regularly and 83.4% for washing hands regularly. In the multivariate logistic regression analysis, stress in the work environment (odds ratio [OR] = 2.09, 95% confidence interval [CI], 1.37-3.20; p < 0.001), financial instability (OR = 1.73, 95% CI, 1.12-2.67; p < 0.05), and low adherence to working remotely (OR = 1.65, 95% CI, 1.06-2.57; p < 0.05) were independently and significantly associated with poor sleep after controlling for the covariates. CONCLUSIONS: One year into the COVID-19 pandemic, the poor sleep rates of HCWs remained high. These results emphasize the need to protect HCWs from work environment stress and financial concerns.

Development and validation of the Japanese version of the Bedtime Procrastination Scale (BPS-J).

BACKGROUND: The average sleep duration of Japanese people is shorter than that of people from other countries, and bedtime procrastination is suspected to be one of the factors contributing to this issue. This study aimed to develop and validate the Japanese version of the Bedtime Procrastination Scale (BPS-J). METHODS: The BPS-J was developed through procedures including the translation and back-translation of the scale, cognitive interviews with 100 participants who reported having experiences of being diagnosed with insufficient sleep syndrome (ISS) or receiving treatment for ISS using open-ended online questionnaires, and expert checking. To investigate the scale's validity and reliability, an online survey was conducted with daytime workers aged 20 - 65 years without a history of sleep disorders other than ISS. Half the participants were retested using the same survey after 14 days. Participants' responses to the Brief Self-Control Scale (BSCS), General Procrastination Scale (GPS), and Munich ChronoType Questionnaire (MCTQ), and data on sleep-related variables such as sleep duration on workdays and the days per week of fatigue or sleep loss, sex, and age, were collected. RESULTS: We analyzed data from 574 participants to assess scale validity. We then analyzed data from 280 participants to determine test-retest reliability. Confirmatory factor analyses revealed that the two-factor model without Item 2 was most suitable for the BPS-J, unlike other language versions. Regardless of the full-item model or the model with Item 2 eliminated, sufficient reliability and significant correlations with the BSCS, GPS, MCTQ, and sleep-related variables such as sleep duration per night on work days, days per week of feeling fatigued, and days per week of sleep loss were observed. Logistic and linear regressions showed that the relationships between the BPS-J, sleep-related variables, and MCTQ were maintained after adjusting for sex and age. CONCLUSION: The BPS-J had sufficient validity and reliability. Further, eliminating Item 2 from the original version of the BPS strengthened the ability to survey Japanese daytime workers.

Association between sleep duration and antibody acquisition after mRNA vaccination against SARS-CoV-2.

Introduction: Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood. Methods: In this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARS-CoV-2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0-44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations. Results: Multivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000-0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible. Discussion: Longer objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2. Study registration: This study is registered at the University Hospital Medical Information Network Center (UMIN: https://www.umin.ac.jp) on July 30, 2021, #UMIN000045009.

Association between health anxiety dimensions and preventive behaviors during the COVID-19 pandemic among Japanese healthcare workers.

Objective: Health anxiety (HA), defined as excessive worry about having a serious medical condition, may affect preventive behaviors during the coronavirus disease 2019 (COVID-19) pandemic. We examined the distinct role of two dimensions of HA-perceived likelihood (probability dimension) and awfulness of illness (awfulness dimension)-in self-protection, as reflected in preventive behaviors during the pandemic. Methods: Participants comprised 657 healthcare workers. Data were collected between February 24 and 26, 2021. The Short Health Anxiety Inventory determined the HA dimensions. Adherence to the government's recommendations for COVID-19 preventive behaviors was self-rated. An independent association between each HA dimension and participants' adherence to the recommendations was examined using multivariable regression. Results: Within the analyzed sample of 560 subjects, severe HA was observed in 9.1 %. The more the participants felt awful, the less frequently they engaged in the recommended preventive behaviors (adjusted odds ratio = 0.993, 95 % confidence interval: 0.989, 0.998, p = 0.003) regardless of their profession, working position, psychological distress, sleep disturbance, and current physical diseases. However, the probability dimension was not associated with their preventive behaviors. Conclusion: The awfulness dimension of HA could be a more sensitive marker of preventive behaviors than the probability dimension. Paying particular attention to the awfulness dimension may help optimize self-protection strategies during the COVID-19 pandemic. A two-dimensional understanding of HA may be useful for the maintenance of the healthcare system and public health as well as healthcare workers' own health.

Relationship between COVID-19-specific occupational stressors and mental distress in frontline and non-frontline staff.

This study investigated the difference in the severity of mental distress and factors contributing to mental distress in frontline and non-frontline healthcare professionals during the coronavirus disease (COVID-19) pandemic. A cross-sectional web-based survey of medical staff collected by snow-ball sampling was performed in Japan in October 2020 using the Kessler Psychological Distress Scale (K6) as an outcome measure for mental distress. Originally developed items asking about the degree of change in psychological and physical burdens, COVID-19-related fear, and experience of discrimination were obtained. The median score of the K6 was 7 in the frontline staff group (n = 86) and 6 in the non-frontline staff group (n = 504), without a statistically significant difference. Multiple regression analyses showed that among the participants, an increase in psychological burden and COVID-19-related fear was significantly associated with mental distress in both groups. Experience of discrimination was significantly associated with mental distress only in the frontline staff group. However, an increase in physical burden was significantly associated with mental distress only in the non-frontline staff group. The results indicate that the factors contributing to mental distress between frontline and non-frontline staff can be different, although the severity of mental distress is comparable between them.

Magnetic Resonance Spectroscopy in the Ventral Tegmental Area Distinguishes Responders to Suvorexant Prior to Treatment: A 4-Week Prospective Cohort Study.

Background: The ventral tegmental area (VTA; a dopaminergic nucleus) plays an important role in the sleep-wake regulation system including orexin system. In addition to neuronal activity, there is increasing evidence for an important role of glial cells (i.e., astrocytes and microglia) in these systems. The present study examined the utility of magnetic resonance spectroscopy (MRS) for detecting neural and/or glial changes in the VTA to distinguish responders from non-responders before treatment with the orexin receptor antagonist suvorexant. Methods: A total of 50 patients were screened and 9 patients were excluded. The remaining 41 patients with insomnia who have or not a psychiatric disease who were expected to receive suvorexant treatment were included in this study. We compared MRS signals in the VTA between responders to suvorexant and non-responders before suvorexant use. Based on previous reports, suvorexant responders were defined as patients who improved ≥3 points on the Pittsburgh Sleep Quality Index after 4 weeks of suvorexant use. MRS data included choline (reflects non-specific cell membrane breakdown, including of glial cells) and N-acetylaspartate (a decrease reflects neuronal degeneration). Results: Among 41 examined patients, 20 patients responded to suvorexant and 21 patients did not. By MRS, the choline/creatine and phosphorylcreatine ratio in the VTA was significantly high in non-responders compared with responders (p = 0.039) before suvorexant treatment. There was no difference in the N-acetylaspartate/creatine and phosphorylcreatine ratio (p = 0.297) between the two groups. Conclusions: Changes in glial viability in the VTA might be used to distinguish responders to suvorexant from non-responders before starting treatment. These findings may help with more appropriate selection of patients for suvorexant treatment in clinical practice. Further, we provide novel possible evidence for a relationship between glial changes in the VTA and the orexin system, which may aid in the development of new hypnotics focusing on the VTA and/or glial cells.

Psychosis in a primary hyperparathyroidism patient with mild hypercalcemia: A case report.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and an elevated level of serum parathyroid hormone (PTH). PHPT presents with a complex set of renal, skeletal, and neuropsychological symptoms. Parathyroidectomy (PTX) is a radical treatment that is recommended for all physically symptomatic patients with PHPT. However, psychiatric symptoms are not considered as an indication for surgery. There remains an important issue from the view of perioperative management of whether PTX should be performed with the presence of uncontrolled psychiatric symptoms or deferred until severe psychiatric symptoms have been controlled. We report a case of mild hypercalcemia that caused severe psychosis in PHPT, which improved dramatically following PTX and resulted in successful postoperative management. PATIENT CONCERN: Our patient was a 68-year-old Japanese woman. She was diagnosed with PHPT, which was triggered by mild hypercalcemia. She was due to receive an operation for osteoporosis and kidney stones. She had severe psychosis, despite medication. Blood examinations revealed mild hypercalcemia (10.4 mg/dL, 8.8-10.1 mg/dL) and elevated serum levels of intact PTH (184.0 pg/mL, 10-65 pg/mL). DIAGNOSIS: She was diagnosed with severe psychosis caused by mild hypercalcemia in PHPT. INTERVENTIONS: Although she was treated with 37.5 mg quetiapine and 2 mg risperidone daily, she was excessively sedated and rejected oral treatment. Therefore, we decided to perform the operation. OUTCOMES: Immediately following surgery, serum levels of calcium, and intact PTH were normalized. Her psychotic symptoms ceased completely 5 days after surgery. CONCLUSION: We emphasize that PHPT presents with various severe psychiatric symptoms, even in mild hypercalcemia. Psychiatric symptoms may be the only salient symptoms in PHPT, and thus clinicians should suspect PHPT in patients with psychiatric symptoms and mild hypercalcemia. Furthermore, PTX is recommended for PHPT-even in the presence of severe uncontrolled psychiatric symptoms, which carries risks for postoperative management-because psychiatric symptoms are expected to improve and good postoperative management is possible.

Prompt improvement of difficulty with sleep initiation and waking up in the morning and daytime somnolence by combination therapy of suvorexant and ramelteon in delayed sleep-wake phase disorder: a case series of three patients.

Patients with delayed sleep-wake phase disorder (DSWPD) suffer from difficulties in sleep initiation at night, difficulties in waking up at the socially required time, and daytime somnolence. About half of the patients resist conventional light therapy and melatonin therapy. Therapy using hypnotics is not recommended due to its adverse effects. Recently, suvorexant, an orexin receptor antagonist, has become available for clinical use. The drug is relatively safer than traditional hypnotics such as benzodiazepines. We report three DSWPD patients who were successfully treated by the combination therapy of suvorexant and ramelteon. The first case was a 19-year-old woman who was experiencing difficulties in sleep initiation, difficulty in waking up in the morning, and daytime somnolence. She showed a prompt response to the combination therapy of suvorexant and ramelteon. Her sleep phase advanced, and her daytime somnolence reduced. The second and third cases were 21-year-old and 17-year-old men, respectively, who also showed significant sleep phase advances. Although case 2 was resistant to ramelteon treatment, his sleep phase advanced after suvorexant started. His difficulty in falling asleep and his habit of daytime napping disappeared after the combination therapy of suvorexant and ramelteon was started. Case 3 also showed a prompt response. His difficulties in falling asleep and waking up in the morning were ameliorated immediately after suvorexant with ramelteon was started. No obvious side effects were observed. Therapy using the combination therapy of suvorexant and ramelteon might be a reasonable option for DSWPD patients.

Real-World Preventive Effects of Suvorexant in Intensive Care Delirium: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to examine the effects of suvorexant on delirium prevention in a real-world setting. Previous studies have demonstrated the efficacy of suvorexant for delirium prevention in limited randomized clinical trial settings; however, its effectiveness in everyday clinical settings remains unknown. METHODS: A single-center, retrospective cohort study was conducted in the intensive care unit of an academic hospital. Patients (aged ≥ 3 years) admitted from January 2016 to December 2018 were eligible if they stayed in the intensive care unit for at least 72 hours. Suvorexant was prescribed by the attending physician for insomnia as part of everyday clinical practice. A Cox proportional hazards regression analysis was conducted on delirium-free survival for suvorexant users, adjusting for delirium-related covariates. As part of routine clinical practice, the Confusion Assessment Method for the Intensive Care Unit was used to detect the existence of delirium at least twice daily throughout the intensive care unit stay. RESULTS: There were 699 patients-84 suvorexant users and 615 suvorexant nonusers. Delirium was detected in 214 patients. Delirium prevalence was significantly lower in suvorexant users than in nonusers (17.9% vs 32.4%, respectively; P = .007). Cox regression analysis revealed a significantly lower hazard ratio (0.472; 95% CI, 0.268-0.832; P = .009) of delirium in suvorexant users than in nonusers. Trazodone also had a preventive effect on delirium (hazard ratio 0.345; 95% CI, 0.149-0.802; P = .013). CONCLUSIONS: The present study extends to real-world settings previous findings that suvorexant is effective for delirium prevention.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms.

BACKGROUND: Fibroblast Growth Factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and prodifferentiation of neurons. METHOD: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis of schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. RESULTS: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats, serum levels were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of Unconjugated Bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 in terms of serum levels in all the rats studied. CONCLUSION: Since it is known that FGF2 regulates dopaminergic neurons and have antineuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which imbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

Parvalbumin-positive GABAergic interneurons deficit in the hippocampus in Gunn rats: A possible hyperbilirubinemia-induced animal model of schizophrenia.

A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. Importantly, these alterations in GABAergic neurons are not global, which means they are more prevalent among distinct subclasses of interneurons, including those that express the calcium binding protein parvalbumin. A decreased expression of parvalbumin in the hippocampus is a consistent observation not only in postmortem human schizophrenia patients, but also in a diverse number of rodent models of the disease. Meanwhile, previously we reported that the congenital hyperbilirubinemia model rats (Gunn rats), which is a mutant of the Wistar strain, showed behavioral abnormalities, for instance, hyperlocomotor activity, deficits of prepulse inhibition, inappropriate social interaction, impaired recognition memory similar with several rodent models of schizophrenia. Several animal studies linked the importance of palvalbumin in relation to abnormal hippocampal activity and schizophrenia-like behavior. Here, we show that parvalbumin positive cell density was significantly lower in the CA1, CA3 and the total hippocampus of Gunn rats (congenital hyperbilirubinemia model rats) compared to Wistar control rats. The correlations between serum UCB levels and loss of PV expression in the hippocampus were also detected. The decreases in the PV-expression in the hippocampus might suggest an association of the behavioral abnormalities as schizophrenia-like behaviors of Gunn rats, compared to the Wistar control rats.

Electroconvulsive shock restores the decreased coverage of brain blood vessels by astrocytic endfeet and ameliorates depressive-like behavior.

BACKGROUND: Although growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms. METHODS: After electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5. RESULTS: Gunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats. CONCLUSIONS: ECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels.

Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder: A Prospective Open-Label Trial.

AIM: Up to 60% of depressed patients do not obtain sufficient relief from a course of antidepressant therapy, and these treatment-resistant major depressive disorder (TRD) patients are at increased risk for relapse, chronicity, persistent psychosocial impairments, and suicide. Probiotics actively participate in treatment of neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and depression remains unclear. We performed a prospective study to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588). METHODS: This was an 8-week open-label study to evaluate the efficacy and safety of CBM588 in combination with antidepressants in adult patients diagnosed with TRD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Forty antidepressant-treated inpatients were included. Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n = 20). The primary endpoint was the change in the 17-item Hamilton Depression Rating Scale score from baseline to week 8. Secondary end points were changes in the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from baseline to week 8. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. RESULTS: CBM588 (60 mg/d) in combination with antidepressants (flvoxamine, paroxetine, escitalopram, duroxetine, and sertraline) provided significant improvement in depression. All patients completed the trial, and 70% responded to treatment; the remission rate was 35.0%. No serious adverse events occurred. CONCLUSIONS: These preliminary data suggest that CBM588 in combination with antidepressants is effective and well tolerated in the treatment of TRD. Further studies using a larger, double-blind, parallel-group design are warranted to confirm these findings.

Cognitive Behavioral Therapy for Insomnia as Adjunctive Therapy to Antipsychotics in Schizophrenia: A Case Report.

The authors present the case of a 38-year-old man with schizophrenia and with severe insomnia, who attempted suicide twice during oral drug therapy with risperidone. The patient slept barely 2 or 3 h per night, and he frequently took half days off from work due to excessive daytime sleepiness. As a maladaptive behavior to insomnia, he progressively spent more time lying in bed without sleeping, and he repeatedly thought about his memories, which were reconstructed from his hallucinations. His relatives and friends frequently noticed that his memories were not correct. Consequently, the patient did not trust his memory, and he began to think that the hallucinations controlled his life. During his insomniac state, he did not take antipsychotic drugs regularly because of his irregular meal schedule due to his excessive daytime sleepiness. The authors started cognitive behavioral therapy for insomnia (CBT-i) with aripiprazole long acting injection (LAI). CBT-i is needed to be tailored to the patient's specific problems, as this case showed that the patient maladaptively use chlorpromazine as a painkiller, and he exercised in the middle of the night because he believed he can fall asleep soon after the exercise. During his CBT-i course, he learned how to evaluate and control his sleep. The patient, who originally wanted to be short sleeper, began to understand that adequate amounts of sleep would contribute to his quality of life. He finally stopped taking chlorpromazine and benzodiazepine as sleeping drugs while taking suvorexant 20 mg. Through CBT-i, he came to understand that poor sleep worsened his hallucinations, and consequently made his life miserable. He understood that good sleep eased his hallucinations, ameliorated his daytime sleepiness and improved his concentration during working hours. Thus, he was able to improve his self-esteem and self-efficacy by controlling his sleep. In this case report, the authors suggest that CBT-i can be an effective therapy for schizophrenia patients with insomnia to the same extent of other psychiatric and non-psychiatric patients.

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test.

INTRODUCTION: Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia-like behavior. METHODS: As it has been suggested that major depression involves glial activation associated with neuroinflammation, we examined whether Gunn rats show depression-like behavior using the forced swimming test (FST) and the tail suspension test (TST). In addition, we quantitatively evaluated both microgliosis and astrogliosis in the hippocampus of Gunn rats using immunohistochemistry analysis of the microglial marker ionized calcium-binding adaptor molecule (Iba) 1 and the astrocytic marker S100B. RESULTS: Both the FST and TST showed that immobility time of Gunn rats was significantly longer than that of normal control Wistar rats, indicating that Gunn rats are somewhat helpless, a sign of depression-like behavior. In the quantification of immunohistochemical analysis, Iba1immunoreactivity in the dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1-positive cells in the CA1 and CA3 were significantly increased in Gunn rats compared to Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of S100B-positive cells in the DG and CA3 were significantly increased in Gunn rats compared to Wistar rats. CONCLUSION: Our findings suggest that both microglia and astrocyte are activated in Gunn rats and their learned helplessness could be related to glial activation.

Remission of Psychosis in Treatment-Resistant Schizophrenia following Bone Marrow Transplantation: A Case Report.

The authors present the case of a 24-year-old male with treatment-resistant schizophrenia, with predominant severe delusion and hallucination, who received bone marrow transplantation (BMT) for acute myeloid leukemia. After BMT, he showed a remarkable reduction in psychotic symptoms without administration of neuroleptics. He also showed drastic improvement in social functioning. Follow-up evaluations 2 and 4 years after BMT showed persistent significant improvement of the psychotic state and social functioning. Recent findings show that the major underlying pathogenic mechanism of schizophrenia is immune dysregulation. Thus, conceptually, BMT, a cellular therapy, that facilitates the counteractive processes of balancing inflammation by immune regulation, could produce beneficial clinical effects in patients with treatment-resistant schizophrenia. Further studies are required to define the true benefits of BMT for the possible curative treatment of schizophrenia.