Structure-activity relationship studies of tetrahydroquinolone derivatives as GPR41 modulators.

GPR41, a G protein-coupled receptor, serves as a sensor for short-chain fatty acids and plays a crucial role in regulating multiple physiological processes such as the maintenance of metabolic and immune homeostasis. Therefore, the modulation of GPR41 has garnered attention as a potential strategy for the treatment of various disorders. We conducted a structure-activity relationship study on a lead tetrahydroquinolone derivative bearing a 2-(trifluoromethoxy)benzene group that displayed antagonistic activity toward GPR41. Modification of the aryl group attached to the furan moiety revealed that derivatives containing di- or trifluorobenzene, instead of 2-(trifluoromethoxy)benzene, exhibited agonistic activity toward GPR41, comparable with the reported agonistic modulator AR420626. These results suggest that the aryl group plays a pivotal role in regulating the activity of compounds toward GPR41, providing valuable insights for the design of GPR41 modulators.

Effects of Subjective Social Status and Self-Esteem in the Association Between Childhood Abuse and Adulthood Anxiety.

Background: Subjective social status influences anxiety, but at present, the mechanism is not fully understood. It has been reported that negative childhood experiences, such as abuse, can influence depressive symptoms through subjective social status and personality traits, such as self-esteem. A similar mechanism is presumed to underlie anxiety symptoms in adulthood. Therefore, we hypothesized that subjective social status and self-esteem are intermediate factors in the indirect effects of childhood abuse on state anxiety in adulthood, and analyzed the indirect effects via these factors using a path analysis. Subjects and Methods: Child Abuse and Trauma Scale, Subjective Social Status, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory Form Y questionnaires were administered in a self-report format to 404 adult volunteers from January 2014 to August 2014. In addition, a path analysis was conducted to determine whether subjective social status and self-esteem are associated with the indirect effects of childhood abuse on anxiety symptoms in adulthood. Results: Childhood abuse did not directly affect state anxiety in adulthood, but affected state anxiety via subjective social status and self-esteem. Subjective social status affected state anxiety via self-esteem. This model explained 25.2% of the variation in state anxiety in adult volunteers. Conclusion: The present study demonstrated that childhood abuse affects anxiety in adulthood through subjective social status and self-esteem. Therefore, interventions that enhance subjective social status and self-esteem for adults who experienced childhood abuse may help reduce their anxiety.

The evaluation study for social cognition measures in Japan: Psychometric properties, relationships with social function, and recommendations.

AIM: Patients with schizophrenia can have significant subjective difficulties in social cognition, but few undergo testing or treatment for social cognition. The Social Cognition Psychometric Evaluation (SCOPE) study recommends six social cognitive measures; however, the reliability and validity of these measures in different cultural and linguistic areas has not been adequately examined. We examined the psychometric properties of nine social cognitive measures and the relationship to social function, with the aim of determining the level of recommendation for social cognitive measures in clinical practice in Japan. METHODS: For our test battery, an expert panel previously selected nine measures: the Bell Lysaker Emotion Recognition Task (BLERT); Facial Emotion Selection Test (FEST); Hinting Task (Hinting); Metaphor and Sarcasm Scenario Test (MSST); Intentionality Bias Task (IBT); Ambiguous Intentions and Hostility Questionnaire (AIHQ); Social Attribution Task-Multiple Choice (SAT-MC); SAT-MCII; and Biological Motion (BM) task. In total, 121 outpatients with schizophrenia and 70 healthy controls were included in the analysis, and the results were provided to an expert panel to determine the recommendations for each measure. The quantitative psychological indices of each measure were evaluated for practicality, tolerability, test-retest reliability, correlation with social function, and the incremental validity of social function. RESULTS: Hinting and FEST received the highest recommendations for use in screening, severity assessment, and longitudinal assessment, followed by BLERT, MSST AIHQ, SAT-MC, and SAT-MCII, with IBT and BM receiving the lowest recommendations. CONCLUSION: This study provides a uniform assessment tool that can be used in future international clinical trials for social cognitive impairment.

Longitudinal reduction in brain volume in patients with schizophrenia and its association with cognitive function.

Establishing a brain biomarker for schizophrenia is strongly desirable not only to support diagnosis by psychiatrists but also to help track the progressive changes in the brain over the course of the illness. A brain morphological signature of schizophrenia was reported in a recent study and is defined by clusters of brain regions with reduced volume in schizophrenia patients compared to healthy individuals. This signature was proven to be effective at differentiating patients with schizophrenia from healthy individuals, suggesting that it is a good candidate brain biomarker of schizophrenia. However, the longitudinal characteristics of this signature have remained unclear. In this study, we examined whether these changes occurred over time and whether they were associated with clinical outcomes. We found a significant change in the brain morphological signature in schizophrenia patients with more brain volume loss than the natural, age-related reduction in healthy individuals, suggesting that this change can capture a progressive morphological change in the brain. We further found a significant association between changes in the brain morphological signature and changes in the full-scale intelligence quotient (IQ). The patients with IQ improvement showed preserved brain morphological signatures, whereas the patients without IQ improvement showed progressive changes in the brain morphological signature, suggesting a link between potential recovery of intellectual abilities and the speed of brain pathology progression. We conclude that the brain morphological signature is a brain biomarker that can be used to evaluate progressive changes in the brain that are associated with cognitive impairment due to schizophrenia.

Regiospecificity of Immobilized Candida antarctica Lipase B (CAL-B) towards 2,3-Diacyl-1-O-alkyl Glyceryl Ether in Ethanol.

Highly pure 2,3-dioleoyl-1-O-alkyl glyceryl ether (DOGE), whose 1-position is a lipase-tolerant ether bond, was chemically synthesized and its detailed regioselectivity and acyl transfer were confirmed. During ethanolysis using immobilized Candida antarctica lipase B (CAL-B) with DOGE as the substrate, monooleoyl-1-O-alkyl glyceryl ethers (MOGEs) and a few 1-alkyl glyceryl ethers were formed upon consumption of the substrate. The structure of MOGE was confirmed using nuclear magnetic resonance spectroscopy and only the isomer of 2-MOGE was formed, indicating that CAL-B has complete α- regiospecificity. During ethanolysis, 3-MOGE was formed via acyl migration. These results indicate that the formation of 1-alkyl glyceryl ethers is not due to the imperfect regiospecificity of CAL-B, but rather due to ethanolysis of the formed 3-MOGE. The ethanolysis rate at the 3-α-position of DOGE was faster and the rate of acyl transfer was slightly slower for chain lengths greater than 14. These results show for the first time that both deacylation at the 3-position and acyl migration from the 2- to 3-position are affected by the structure of 1-position.

Gold(I)-Catalyzed Cascade Cyclization of Alkynyl Indoles for the Stereoselective Construction of the Quaternary Carbon Center of Akuammiline Alkaloids.

A gold-catalyzed cyclization reaction of alkynyl-indoles has been developed for the stereoselective construction of the quaternary carbon center of fused indolines. This reaction efficiently produces fused indolines via diastereoselective 6-endo-dig cyclization controlled by a bulky TIPS group, followed by nucleophilic attack of the carboxy group on the resulting imine. The lactone moiety of the fused indoline can be reductively cleaved to produce a tricyclic indoline, which could be useful for the synthesis of akuammiline alkaloids.

Risk factors for abnormal glucose metabolism during antipsychotic treatment: A prospective cohort study.

Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05-4.05), clozapine (HR = 4.25, 95% CI = 1.56-11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21-16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02-2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02-2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication.

Neurobiological correlation between phosphorylated tau and mood symptoms in memory clinic patients.

BACKGROUND: Alzheimer's disease (AD) dementia and mild cognitive impairment are characterised by impaired cognition accompanied by neuropsychiatric symptoms (NPS) relating to mood, including depression, anxiety, and apathy. However, the utility of AD biomarkers for predicting mood symptoms of NPS remains controversial. Herein, we analyzed the relationship between phosphorylated tau (p-tau) and depression, anxiety, and apathy of NPS. We also examined the influence of genetic factors such as apolipoprotein E (APOE) ε4 on these relationships. METHODS: We conducted a cross-sectional survey in older patients (n = 122) with normal cognition (n = 12), mild cognitive impairment (n = 46), and AD (n = 64) strictly diagnosed by the board of psychiatrists and neurologists of Hokkaido University. NPS of the patients were assessed using the Neuropsychiatric Inventory Questionnaire (NPI). All patients also received a lumbar puncture to obtain cerebral spinal fluid for assessment of p-tau. The inverse probability weighting method was used to adjust for demographic differences between the p-tau present group and the p-tau absent group. RESULTS: There was an association between p-tau accumulation and decreased incidence of depression and apathy. APOE ε4 non-carriers also showed a trend toward a negative association between p-tau and depression, which was not evident in APOE ε4 carriers. CONCLUSIONS: We provide new evidence for a negative correlation between p-tau and depression and apathy of NPS, which may be influenced by APOE ε4. Future longitudinal studies are required to confirm the utility of p-tau for predicting the course of mood symptoms in patients with cognitive decline.

Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study.

AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

Sub-nanometric High-Entropy Alloy Cluster: Hydrogen Spillover Driven Synthesis on CeO2 and Structural Reversibility.

High-entropy alloy (HEA) nanoparticles (NPs) have attracted significant attention as promising catalysts owing to the various unique synergistic effects originating from the nanometer-scale, near-equimolar mixing of five or more components to produce single-phase solid solutions. However, the study of sub-nanometer HEA clusters having sizes of less than 1 nm remains incomplete despite the possibility of novel functions related to borderline molecular states with discrete quantum energy levels. The present work demonstrates the synthesis of CeO2 nanorods (CeO2-NRs) on which sub-nanometer CoNiCuZnPd HEA clusters were formed with the aid of a pronounced hydrogen spillover effect on readily reducible CeO2 (110) facets. The CoNiCuZnPd HEA sub-nanoclusters exhibited higher activity during the reduction of NO by H2 even at low temperatures compared with the corresponding monometallic catalysts. These clusters also showed a unique structural reversibility in response to repeated exposure to oxidative/reductive conditions, based on the sacrificial oxidation of the non-noble metals. Both experimental and theoretical analyses established that multielement mixing in quantum-sized regions endowed the HEA clusters with entirely novel catalytic properties.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Feasibility of a wrist-worn wearable device for estimating mental health status in patients with mental illness.

Object: Real-world data from wearable devices has the potential to understand mental health status in everyday life. We aimed to investigate the feasibility of estimating mental health status using a wrist-worn wearable device (Fitbit Sense) that measures movement using a 3D accelerometer and optical pulse photoplethysmography (PPG). Methods: Participants were 110 patients with mental illnesses from different diagnostic groups. The study was undertaken between 1 October 2020 and 31 March 2021. Participants wore a Fitbit Sense on their wrist and also completed the State-Trait Anxiety Inventory (STAI), Positive and Negative Affect Schedule (PANAS), and EuroQol 5 dimensions 5-level (EQ-5D-5L) during the study period. To determine heart rate (HR) variability (HRV), we calculated the sdnn (standard deviation of the normal-to-normal interval), coefficient of variation of R-R intervals, and mean HR separately for each sleep stage and the daytime. The association between mental health status and HR and HRV was analyzed. Results: The following significant correlations were found in the wake after sleep onset stage within 3 days of mental health status assessment: sdnn, HR and STAI scores, HR and PANAS scores, HR and EQ-5D-5L scores. The association between mental health status and HR and HRV was stronger the closer the temporal distance between mental health status assessment and HR measurement. Conclusion: A wrist-worn wearable device that measures PPG signals was feasible for use with patients with mental illness. Resting state HR and HRV could be used as an objective assessment of mental health status within a few days of measurement.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Outpatient visit behavior in patients with epilepsy: Generalized Epilepsy is more frequently non-attendance than Focal Epilepsy.

BACKGROUND: Patients with epilepsy (PWE), especially those with Idiopathic Epilepsy (GE), are at a high risk of disadvantage caused by non-adherence. It has been suggested that medical visit behavior may be a surrogate indicator of medication adherence. We hypothesized that patients with IGE would adhere poorly to visits. METHODS: This was a retrospective study of PWE who visited the Department of Psychiatry and Neurology at Hokkaido University Hospital between January 2017 and December 2019. Demographic and clinical information on PWE were extracted from medical records and visit data from the medical information system. Non-attendance of outpatient appointments was defined as "not showing up for the day of an appointment without prior notice." Mixed-effects logistic regression analysis was conducted with non-attendance as the objective variable. RESULTS: Of the 9151 total appointments, 413 were non-attendances, with an overall non-attendance rate of 4.5%. IGE was a more frequent non-attendance than Focal Epilepsy (FE) (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.17-3.21; p = 0.010). History of public assistance receipt was associated with higher non-attendance (OR 2.04; 95% CI 1.22-3.43; p = 0.007), while higher education (OR 0.64; 95% CI 0.43-0.93; p = 0.021) and farther distance to a hospital (OR 0.33; 95% CI 0.13-0.88; p = 0.022), and higher frequency of visits (OR 0.18; 95% CI 0.04-0.86; p = 0.031) were associated with fewer non-attendances. In a subgroup analysis of patients with GE, women were associated with fewer non-attendance (OR 0.31; 95% CI 0.14-0.72; p = 0.006). CONCLUSIONS: GE was more frequent in the non-attendance group than in the FE group. Among patients with GE, females were found to have non-attendance less frequently; however, there was no clear difference in the odds of non-attendance between Juvenile Myoclonic Epilepsy (JME) and IGE other than JME.

Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia.

AIM: Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision-making (SDM) between patients and health-care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. METHODS: A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta-analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA. RESULTS: The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value-clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%). Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. CONCLUSION: A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

Change of prescription for patients with schizophrenia or major depressive disorder during admission: real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project.

BACKGROUND: Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. METHODS: Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. RESULTS: For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. CONCLUSIONS: It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

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.

Mediation Effects of Social Cognition on the Relationship between Neurocognition and Social Functioning in Major Depressive Disorder and Schizophrenia Spectrum Disorders.

BACKGROUND: In schizophrenia spectrum disorders (SSD), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. METHODS: Using data obtained through an internet survey, 210 patients with SSD or MDD were selected using propensity score matching based on their demographics and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each group. Invariances of the mediation model across the two groups were then analyzed. RESULTS: The SSD and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. CONCLUSION: The role of social cognition in patients with MDD was similar to that in SSD. Social cognition could be a common endophenotype for various psychiatric disorders.

Assessment of electroencephalography modification by antipsychotic drugs in patients with schizophrenia spectrum disorders using frontier orbital theory: A preliminary study.

AIM: Schizophrenia is characterized by an abnormality in electroencephalography (EEG), which can be affected by antipsychotic drugs. Recently, the mechanism underlying these EEG alterations in schizophrenia patients was reframed from the perspective of redox abnormalities. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) can be calculated using a computational method and may be useful for evaluating the antioxidant/prooxidant effect of antipsychotic drugs. Thus, we examined the association between the effects of antipsychotic monotherapy on quantitative EEG and HOMO/LUMO energy. METHODS: We used medical report data including EEG results of psychiatric patients admitted to Hokkaido University Hospital. We extracted the EEG records of patients diagnosed with a schizophrenia spectrum disorder undergoing antipsychotic monotherapy during the natural course of treatment (n = 37). We evaluated the HOMO/LUMO energy of all antipsychotic drugs using computational methods. Multiple regression analyses were used to examine the relationship between the HOMO/LUMO energy of all antipsychotic drugs and spectral band power in all patients. Statistical significance was set at p < 6.25 × 10-4 adjusted with Bonferroni correction. RESULTS: We showed that the HOMO energy of all antipsychotic drugs had weak positive correlations with delta- and gamma-band power (e.g., standardized ß = 0.617 for delta in the F3 channel, p = 6.6 × 10-5 ; standardized ß = 0.563 for gamma in the O1 channel, p = 5.0 × 10-4 ). CONCLUSION: Although there may be unexpected bias and confounding factors, our findings suggest that the effect of antipsychotic drugs on EEG may be related to their antioxidant actions.

Effects of electroconvulsive therapy on the use of anxiolytics and sleep medications: a propensity score-matched analysis.

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.