Smaller hypothalamic subregion with paraventricular nucleus in patients with panic disorder.

In panic disorder (PD), functional disturbance of the hypothalamus-pituitary-adrenal (HPA) axis has been considered. However, in neuroimaging studies of PD, the hypothalamus and pituitary gland are poorly studied.We investigated the volume of PD patients' hypothalamus and pituitary gland, enrolling 38 PD patients and 38 healthy controls. Severity of PD was mild to moderate according to the Panic Disorder Severity Scale, and the illness duration was relatively short (median = 2.8 years). The hypothalamus' gray matter was automatically extracted and segmented, whereas the pituitary gland was manually traced. Regarding the hypothalamus, the paraventricular nucleus (PVH), which produces the corticotropin-releasing hormone, was of interest.The volumes of the pituitary and the bilateral anterior-superior hypothalamic subunits, where the PVH would be located, were compared by the multiple regression analyses controlling for age and intracranial content volume. To compensate for limitation in the abovementioned segmentation and analyses, the voxel-based morphometry with small volume correction (VBM-SVC) targeting the whole hypothalamus was also performed.The multiple regression analyses did not find significant effect of PD diagnosis on the volumes. However, in the VBM-SVC analysis, volume reduction of the PVH was suggested in PD even when patients who experienced PD for ≥ 3 years were excluded [peak coordinate (x, y, z = -2, 3, -8), FWE-corrected P = .022 (cluster-level) and 0.003 (peak-level), voxel size = 63]. Our results suggested structural alteration of the PVH in PD patients for the first time, indicating importance of the HPA-axis in PD pathology.

Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial.

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan.

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.

Differences in autonomic nervous system activity between long-acting injectable aripiprazole and oral aripiprazole in schizophrenia.

BACKGROUND: Distinct oral atypical antipsychotics have different effects on autonomic nervous system (ANS) activity. Among them, oral aripiprazole has been linked to dysfunction of the ANS in schizophrenia. Long-acting injectable aripiprazole is a major treatment option for schizophrenia, but the effect of the aripiprazole formulation on ANS activity remains unclear. In this study, we compared ANS activity between oral aripiprazole and aripiprazole once-monthly (AOM) in schizophrenia. METHODS: Of the 122 patients with schizophrenia who participated in this study, 72 received oral aripiprazole and 50 received AOM as monotherapy. We used power spectral analysis of heart rate variability to assess ANS activity. RESULTS: Patients who received oral aripiprazole showed significantly diminished sympathetic nervous activity compared with those who received AOM. Multiple regression analysis revealed that the aripiprazole formulation significantly influenced sympathetic nervous activity. CONCLUSION: Compared with oral aripiprazole, AOM appears to have fewer adverse effects, such as sympathetic nervous dysfunction.

Development of an individual fitness score (IFS) based on the depression treatment guidelines of in the Japanese Society of Mood Disorders.

AIM: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. METHODS: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. RESULTS: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10-3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). CONCLUSION: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.

Effectiveness of anger-focused emotional management training in reducing aggression among nurses.

AIM: The aim of this study was to conduct a 5-h training programme on anger-focused emotional management for nurses and verify its effectiveness. DESIGN: The study used a one-group pretest-posttest design. METHODS: Participants (N = 283) attended a programme comprising lectures and exercises. The Japanese version of the Buss-Perry Aggression Questionnaire was administered pre-, post- and 3-month posttraining. Regression analyses were used to assess the effects of the programme by gender. RESULTS: For the total aggression score, the difference between the pre- and posttraining scores was -2.827 points and remained at -1.602 points 3-month posttraining. Physical aggression scores decreased posttraining, but the scores increased after 3 months. There were statistically significant gender differences in hostility scores; pre-training scores were slightly higher for men than for women and lower for men after 3 months. Total and physical aggression scores were higher for men than for women. The training programme decreased aggression, and the effect persisted after 3 months.

The psychological distress and suicide-related ideation in hospital workers during the COVID-19 pandemic: Second results from repeated cross-sectional surveys.

The COVID-19 pandemic has been affecting the mental health of hospital workers. During the prolonged pandemic, hospital workers may experience much more severe psychological distress, leading to an increased risk of suicide. This study aimed to investigate changes in psychological effects on hospital workers over 12 months from the beginning of the pandemic and clarify factors associated with psychological distress and suicide-related ideation 1-year after the pandemic's beginning. These repeated, cross-sectional surveys collected demographic, mental health, and stress-related data from workers in 2 hospitals in Yokohama, Japan. The first survey, conducted in March-April 2020, contained the 12-item General Health Questionnaire (GHQ-12) assessing general distress and the Impact of Event Scale-Revised (IES-R) assessing event-related distress. In the second survey in March 2021, hospital workers at the same two hospitals were reassessed using the same questionnaire, and Item 9 of the Patient Health Questionnaire (PHQ-9) was added to assess their suicide-related ideation. The findings of the first and second surveys revealed that the average score of GHQ-12 (3.08 and 3.73, respectively), the IES-R total score (6.8 and 12.12, respectively), and the prevalence rates of severe general distress (35.0% and 44.0%, respectively) and severe event-related distress (7.0% and 17.1%, respectively) deteriorated. The second survey showed that 8.6% of the hospital workers were experiencing suicide-related ideation. Both the general and event-related distress were associated with suicide-related ideation. In these surveys, mental health outcomes among the hospital workers deteriorated over one year from the pandemic's beginning, and their severe psychological distress was the risk factor for the suicide-related ideation. Further studies are needed to compare the psychological effects on hospital workers during and after the prolonged pandemic and to explore appropriate measures to support hospital workers' mental health.

Obsessive-Compulsive Disorder with Psychotic Features: Is It a Clinical Entity?

(1) Background: Even though the comorbidity of obsessive-compulsive disorder (OCD) and a psychotic disorder (PD), such as schizophrenia, is being increasingly recognized, the impact of this comorbidity on the clinical presentation, including insight into obsessive-compulsive symptoms and the functioning of OCD, remains unclear. (2) Methods: To investigate clinical differences between OCD patients with and without PD, 86 Japanese outpatients who met the DSM-IV-TR criteria for OCD were recruited and divided into two groups: 28 OCD patients with PD, and 58 OCD patients without PD. The two groups were cross-sectionally compared in terms of their sociodemographic profiles and clinical characteristics, including the DSM-IV-TR insight specifier and the Global Assessment of Functioning (GAF). (3) Results: The results showed that OCD patients with PD scored lower on both the insight and GAF assessments. (4) Conclusions: The present study suggests that comorbid PD in OCD is a clinical entity.

Characteristics of the treatments for each severity of major depressive disorder: A real-world multi-site study.

PURPOSE: In the treatment guidelines for major depressive disorder (MDD), the recommended treatment differs based on the severity. However, the type of treatment provided based on the severity of MDD in real-world clinical practice has not been investigated. In this study, we clarified the actual situation of MDD treatment in clinical practice and compared the treatment based on the severity of MDD. METHODS: We used data from 1484 patients with MDD at discharge from October 2016 to March 2020. RESULTS: The number of psychotropic prescriptions tended to be lower in those diagnosed with MDD in the severe group compared to in the non-severe group. There were significant differences among the three groups (mild, moderate/severe, and psychotic) in the percentage of patients who were not prescribed antipsychotics (p = 1.9 ×10-6), a combination of antipsychotics and antidepressants (p = 5.0 ×10-4), and the implementation rate of modified electroconvulsive therapy (m-ECT) (p = 3.4 ×10-9). The percentage of patients with a severe diagnosis who underwent m-ECT was higher, which corresponded to the severity. CONCLUSION: Our findings showed that the use of psychotropics decreased when the severity of MDD was diagnosed, and the rate of a combination of antipsychotics and antidepressants and the implementation rate of m-ECT increased with the severity. However, this study suggests that there is still an evidence-practice gap in the treatment of MDD in Japan, and guidelines are only partially adhered to in the treatment of depression.

Structural brain abnormalities in adolescent patients with anorexia nervosa at both the acute and weight-recovered phase.

Previous cross-sectional studies have reported that adolescent patients with anorexia nervosa (AN) showed global gray matter volume (GMV) reductions at the acute phase which were restored at the weight-recovered phase, compared with healthy controls (HC). However, few studies have investigated white matter volume (WMV) or cortical thickness in the context of AN, and results have been inconsistent. Voxel-based morphometry analyses for GM and WM, and cortical thickness analyses for GM were conducted in 31 adolescent patients with AN (vs. 18 HC) in the acute phase, and 16 patients with AN (vs. 13 HC) in the follow-up weight-recovered phase, over an approximately 1-year follow-up interval. At the acute phase, the AN patients showed significant reductions of GMVs and cortical thickness in widespread brain regions, compared with HC. Significant WMV reductions were identified in the bilateral superior longitudinal fascicle, superior thalamic radiation, corona radiata, and fornix, pons, and medulla in the patients. At the weight-recovered phase, the AN patients showed a significant GMV reduction in the left hippocampus, and a WMV reduction in the pons, compared with the HC. There was no difference in cortical thickness between two groups at the weight-recovered phase. In conclusion, the widespread volumetric reductions in GM and WM, and reduced cortical thickness observed in AN patients in the acute phase were not evident in the follow-up weight-recovered phase. The volume reductions observed in the hippocampus and pons in the weight-recovered phase could potentially reflect delayed neurogenesis or recovery from starvation in the AN patients.

Hypnotic medication use among inpatients with schizophrenia and major depressive disorder: results of a nationwide study.

STUDY OBJECTIVES: To investigate the proportion of inpatients with schizophrenia and major depressive disorder prescribed hypnotic medication, and the association between such medication and the use of other antipsychotic agents. METHODS: This was a nationwide cross-sectional study performed as part of the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment' (EGUIDE) project. Data from 2146 inpatients with schizophrenia and 1031 inpatients with major depressive disorder were analyzed. All types and dosages of psychotropic drugs were recorded and the data at the time of discharge were analyzed. Associations between the use of hypnotic medication and other antipsychotic agents were evaluated using multivariate logistic regression analyses. RESULTS: The proportions of schizophrenia patients who were prescribed any and two or more hypnotic agents were 55.7% and 17.6%, respectively, and the corresponding proportions for patients with major depressive disorder were 63.6% and 22.6%, respectively. In schizophrenia patients, multivariate logistic regression analyses showed that two or more antipsychotics, anticholinergic drugs, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. In patients with major depressive disorder, multivariate logistic regression analyses revealed that two or more antidepressants, two or more antipsychotics, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. CONCLUSIONS: Prescription of hypnotic agents was found to be highly frequent among inpatients with psychiatric disorders. Prescription of two or more main antipsychotic agents was commonly associated with the use of hypnotic medication for both schizophrenia and major depressive disorder.

Japanese Project for Telepsychiatry Evaluation during COVID-19: Treatment Comparison Trial (J-PROTECT): Rationale, design, and methodology.

INTRODUCTION: The COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. METHODS: The targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a "telepsychiatry group" (at least 50% of treatments to be conducted using telemedicine, with at least one face-to-face treatment [FTF] within six months) or an "FTF group" (all treatments to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. DISCUSSION: This study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. TRIAL REGISTRATION: jRCT1030210037, Japan Registry of Clinical Trials (jRCT).

The psychological effects of COVID-19 on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship.

The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that 'Feeling of being isolated and discriminated' was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.

Smaller volume of right hippocampal CA2/3 in patients with panic disorder.

The hippocampus is thought to play an important role in conveying contextual information to the amygdala as the neural basis of panic disorder (PD). Previous studies have revealed functional abnormalities in the hippocampus in patients with PD compared with healthy control subjects (HC), but no study has reported volume abnormalities in the hippocampus or evaluated minute structural changes in the hippocampus in such patients. We thus investigated volume abnormalities in the subfields of the hippocampus to better understand the neurobiological basis of PD. The hippocampus was extracted from structural brain magnetic resonance images obtained from 38 patients with PD and 38 HC and then segmented into six subfields. The relative volume of each subfield was compared between the two groups. The severity of symptoms was assessed using the Panic Disorder Severity Scale (PDSS) and social functioning was assessed using the Global Assessment of Functioning (GAF) scale. Our results revealed that patients with PD had a significantly smaller volume of the right cornu ammonis (CA) 2/3 hippocampal subfield compared with HC. No significant associations were found between the volumes of the right CA 2/3 and the PDSS or GAF scores in correlation analyses. In conclusion, CA2/3 is thought to be related to contextual memory function, and our results suggest that this particular hippocampal subfield plays a role in the development of PD symptoms.

Exploratory investigation on antibodies to GluN1 and cognitive dysfunction in patients with chronic autoimmune psychosis.

INTRODUCTION: Mild cognitive dysfunction has been implicated in a number of psychiatric diseases and affects social functioning. Although clinical criteria were recently proposed for autoimmune psychosis (AP), biomarkers have not yet been established for the severity and prognosis of cognitive dysfunction. We herein investigated the relationships between 3 types of serum antibodies and cognitive dysfunction in chronic psychiatric patients suspected of AP. METHODS: We included 31 patients suspected of AP and obtained information on their clinical characteristics. Three types of autoantibodies (the anti-N-methyl-D-aspartate receptor (anti-NMDAR Ab), anti-N-terminal of GluN1 (anti-GluN1-NT Ab), and anti-thyroid antibodies) were evaluated in serum. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. We examined the relationships between serum autoantibodies and cognitive dysfunction in patients using multiple regression models. RESULTS: Serum titers of anti-GluN1-NT Ab significantly contributed to the estimated score of working memory (B= -55.85, ß= -0.46, p= 0.01), while no correlation was observed between the other 2 types of antibodies and cognitive function. CONCLUSIONS: The present results indicate the potential of serum anti-GluN1-NT Ab as a biomarker for the severity and prognosis of cognitive dysfunction underlying various psychiatric symptoms in patients with AP. The pathological significance of anti-GluN1-NT Ab needs to be verified in future studies.

Influence of plasma matrix metalloproteinase levels on longitudinal changes in Alzheimer's disease (AD) biomarkers and cognitive function in patients with mild cognitive impairment due to AD registered in the Alzheimer's Disease Neuroimaging Initiative database.

OBJECTIVE: The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS: We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aß42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aß42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS: No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION: High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.

Structural abnormalities in nucleus accumbens in patients with panic disorder.

BACKGROUND: Although the pathogenesis of panic attacks has been well studied in patients with panic disorder (PD), the neurobiological basis of the long-term fear memories and avoidance behavior that are often observed in PD have not been well investigated. Recent animal studies have suggested that nucleus accumbens (NAcc) plays an important role in neurobiological basis of long-term fear memories and avoidance behavior. METHODS: Thirty-eight patients with PD and 38 matched healthy control subjects (HC) participated in this study. Differences in relative volumes and shape deformations of NAcc were evaluated between groups. Correlation analyses were conducted to quantify the association between structural abnormalities in the NAcc and trait, state anxiety measured by the State-Trait Anxiety Inventory (STAI). RESULTS: Significant volume reductions were observed in the bilateral NAcc in the patients with PD, relative to the HC. In terms of shape differences, the PD patients demonstrated significant inward deformation of the NAcc bilaterally, compared to the HC. Degree of shape deformation in the right NAcc was associated with higher scores of the STAI-Trait, and STAI-State measures in the PD patients. LIMITATIONS: All the patients received medication such as Psychotropic drug. CONCLUSION: Patients with PD showed reduced volumes in the NAcc, especially in lateral regions, compared with HC. Furthermore, shape deformation in the right NAcc was associated with trait anxiety and state anxiety, which has been associated with avoidance behavior.

Clinical and brain structural effects of the Illness Management and Recovery program in middle-aged and older patients with schizophrenia.

AIMS: In this study, we implemented the Illness Management and Recovery (IMR) program for middle-aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated. METHODS: The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50-77 years) and mean hospitalization duration was 13.1 years (range, 1-31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups. RESULTS: Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group. CONCLUSIONS: This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle-aged and older inpatients with schizophrenia hospitalized for long periods.