We investigated differences in cognitive and social functioning between patients with schizophrenia who met criteria for recovery or remission and healthy controls. This cross-sectional study included 55 patients with schizophrenia who met recovery or remission criteria and 20 healthy controls. Cognitive function was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J), and social function was assessed using the Japanese version of the Social Functioning Scale. Executive function scores did not differ significantly among the three groups; however, the other primary and composite scores of the BACS-J differed significantly among the three groups. In the post hoc analysis, verbal fluency (VF) and attention and processing speed (AP) were higher in the recovery group compared with the remission group (VF: p = 0.043; AP: p = 0.045). All domains of social functioning differed significantly among the three groups. In the post hoc analysis, significant differences between the recovery and remission groups were observed in interpersonal communication (p = 0.002), prosocial activity (p = 0.005), employment/occupation (p < 0.001), and total score (p = 0.005). These results indicate that VF and AP may be important cognitive domains related to clinical recovery in patients with schizophrenia. Furthermore, social functioning domains that require interaction with others may be more important for recovery than daily living skills.

ABSTRACT Background Several schizophrenia guidelines have been published, showing treatment efficacy. However, no studies have examined recovery and pharmacological therapy or guideline adherence's impact on various schizophrenia states. This study aimed to investigate adherence to pharmacological guidelines across recovery, remission, and non‐remission states in patients with schizophrenia. Methods This cross‐sectional study included 72 patients with schizophrenia who met the criteria for recovery, remission, or non‐remission. Adherence to pharmacological guidelines was measured using the Individual Fitness Score (IFS). Results IFS was significantly higher in the recovery (88.1 ± 18.9) and remission (89.0 ± 16.7) groups than in the non‐remission group (65.59 ± 21.8) (p < 0.01). However, no significant differences were observed between the recovery and remission groups. Receiver operating characteristic analysis identified 72 points on the IFS as a potential cutoff point between remission and non‐remission. Conclusion These results show that higher adherence to pharmacological guidelines may be associated with recovery and remission state, compared with non‐remission state. The cutoff point between remission and non‐remission should be considered preliminary and exploratory because of a small sample. Clinical practice guidelines have been developed to standardize and improve the quality of medical care. Treatments following these guidelines have been reported to be effective.

AIMS:This study aimed to develop a Japanese version of the Movie for the Assessment of Social Cognition (MASC-J) and to conduct a preliminary evaluation of its reliability and validity in adults with autism spectrum disorder (ASD) compared with healthy controls (HCs). METHODS:Thirty adults with ASD and 30 HCs completed the MASC-J, Reading the Mind in the Eyes Test (RMET), Autism-Spectrum Quotient, and Japanese Adult Reading Test. Internal consistency, test-retest reliability, partial convergent validity with the RMET, and discriminative ability using receiver operating characteristic analysis were examined. RESULTS:MASC-J scores were significantly lower in the ASD group than in the HC group. The MASC-J showed acceptable discriminative ability (area under the curve = 0.804), acceptable internal consistency, and excellent test-retest reliability. In the total sample, MASC-J scores correlated with RMET scores, but this association was not significant within either group. In the ASD group, MASC-J scores were positively associated with estimated full-scale IQ. Overmentalizing and absence-of-mentalizing errors were more frequent in the ASD group, whereas undermentalizing errors did not differ between groups. CONCLUSION:These findings provide preliminary support for the MASC-J as a measure of social cognition in Japanese-speaking adults with ASD.

BACKGROUND/OBJECTIVES:Bipolar disorder is characterized by psychosocial dysfunction, cognitive impairment, and incomplete recovery. Although inflammatory and neurotrophic mechanisms have been implicated, their relationships with multidimensional recovery outcomes remain unclear. We examined the relationships of inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) with depressive symptoms, psychosocial functioning, cognitive performance, personal recovery, and quality of life (QOL) in patients with bipolar disorder. METHODS:This cross-sectional study of 24 patients with bipolar disorder assessed depressive symptoms, psychosocial functioning, cognitive functions, personal recovery, and QOL. Plasma tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, IL-2, BDNF, and VEGF-A were measured by assay. RESULTS:Subjective cognitive dysfunction was significantly associated with depressive symptom severity (rho = 0.53, p = 0.0083) and reduced QOL (rho = -0.56, p = 0.0042). Depressive symptoms were also associated with lower WHO-QOL-26 scores (rho = -0.43, p = 0.038). Significant interrelationships were observed among objective cognitive measures, and after false discovery rate (FDR) correction, the associations between FAST and PDQ-5-D, Symbol Check and Codebreaker, and Codebreaker and Trail remained statistically significant. High plasma IL-6 levels were associated with worse executive function (rho = 0.43, p = 0.0068). Higher VEGF levels were associated with better attentional performance (rho = -0.42, p = 0.042). Plasma IL-1β levels were positively associated with QOL (rho = 0.54, p = 0.02). After FDR correction, only the association between IL-1β and QOL remained statistically significant. CONCLUSIONS:This pilot study suggests that there may be associations between cognitive impairment and cytokines, as well as between quality of life and VEGF, in bipolar disorder. Further studies with larger sample sizes are needed.

Aim:The pathophysiology and treatment of sensory hypersensitivity remain unclear. This study aimed to identify a simple behavioral analysis device and animal model evaluating glare sensitivity and to test the effects of psychotropic drugs using this device. Methods:We recorded the response to light stimulation using a light-dark box (LDB) in male mice in mydriatic-induced glare sensitivity (MiG) and normal control (NC) groups. We also investigated the effects of chronic drug administration (aripiprazole, risperidone, and diazepam). For biological analysis, we measured monoamine levels in the hippocampus, prefrontal cortex, amygdala, hypothalamus, and visual cortex using high-performance liquid chromatography (HPLC). Results:"Time spent in the light box" under the condition "dark-reared and a light box with 1000 lux illuminance" showed significantly shorter durations in the MiG compared to the NC. Aripiprazole administration in MiG and diazepam administration in NC and MiG caused a significant decrease in amygdalar serotonin (5-HT). The administered drug in this study did not restore the MiG's time spent in the light box to the same level as the NC. Conclusion:"Time spent in the light box" under the condition "dark-reared and a light box with 1000 lux illuminance" was considered useful as an item for evaluating glare sensitivity. The trends in brain monoamine changes and behavioral analysis suggest that the reduction of 5-HT in the amygdala by aripiprazole and diazepam may be involved in alleviating glare sensitivity and anxiety. However, no significant behavioral change was observed, so aripiprazole/risperidone/diazepam could not be said to function clearly as a treatment for glare sensitivity.

Aim:Major depressive disorder is a growing global concern with limited treatment options. Social stress contributes to its development, yet pharmacological prevention and mitigation remain underexplored. This study examined the effects of Saiko-ka-ryukotsu-borei-to (SRBT) on depressive and anxiety-like behaviors in mice exposed to social defeat stress (SDS). Methods:C57BL/6J mice were subjected to daily 10-min interactions with larger, more aggressive ICR mice for 10 consecutive days to induce SDS. Immediately following each session, mice were orally administered SRBT, fluoxetine (Flu), or saline (Sal), and were assigned to the SD-SRBT, SD-Flu, and SD-Sal groups, respectively. Mice that received Sal without SDS exposure served as the normal control (NC) group. On the 11th day, behavioral assessments, including the elevated plus maze (EPM) test, tail suspension test (TST), and social interaction test (SIT), were conducted across the four groups. Plasma corticosterone levels were also measured. Results:SDS significantly increased anxiety-like behavior in the EPM, as shown by reduced open arm time in the SD-Sal and SD-Flu groups. This effect was less evident in the SD-SRBT group. Although the SD-Flu group showed similar anxiety-like behavior to the SD-Sal group, no significant difference in open arm time was observed. SDS did not induce social avoidance or depressive-like behavior in the SIT or TST, nor did it alter plasma corticosterone levels. Conclusion:This study suggested that SRBT has the potential to mitigate anxiety caused by social stress. However, further ongoing evaluation and investigation are required to assess the effectiveness of SRBT.

Abstract Background Recovery is considered one of the goals for patients with schizophrenia. However, a systematic review reported that the rate of recovery was 13.5% [1], and this has remained low compared with the rate of remission [2]. Thus, achieving recovery is a more difficult goal than achieving remission in schizophrenia patients. In Japan, the guideline for pharmacological therapy for schizophrenia has been published by the Japanese Society of Neuropsychopharmacology [3]. This guideline highly recommended second-generation antipsychotics monotherapy without the combination of other psychotropic drugs for patients in the acute and maintenance terms of schizophrenia. Individual fitness score (IFS) is a tool to evaluate the treatment for schizophrenia according to the guideline [4]. IFS is calculated as follows: 100 points were given for complete adherence to the guideline, and points were subtracted from the total score for any administered treatment that was not recommended. Previous studies using IFS have reported that adherence to the guideline contributes to improving psychiatric symptoms for patients with schizophrenia [5], but it is unclear whether the adherence could contribute to achieving recovery or improving functional outcome for patients with schizophrenia. Aims & Objectives The aim of this study was to compare the different states of schizophrenia patients (recovery, remission, non-remission) with IFS, and to assess whether adherence to the guideline could contribute to achieving recovery. Method This study was a cross-sectional study that included 64 Japanese schizophrenia patients. Inclusion criteria were individuals aged 20 to 65 who have not changed antipsychotics for at least 3 months and are not taking anticholinergics. Recovery was defined based on Liberman’ s criteria [6], and remission was defined based on Andreasen’ s criteria [7]. Non-remission was defined as not meeting the recovery, remission, and treatment-resistant criteria. We used the Brief Psychiatric Rating Scale (BPRS) [8] and Calgary Depression Scale (CDSS) [9] for assessment of psychiatric symptoms. This study was approved by the Fukuoka University Medical Ethics Committee (U-21-11-018), and verbal and written consent was obtained from all participants. Statistical analysis was performed using SPSS (ver. 27) with χ-square test, one-way analysis of variance, Kruskal– Wallis test, and receiver operating characteristic, with P<0.05. Results In the demographics and clinical characteristics of each group, no significant difference was found except for employment, number of admissions, BPRS score, and CDSS score. First, the IFS was significantly different among the three groups. The IFS in the recovery and remission groups were significantly higher than that in the non-remission group. However, there was no significantly difference in IFS between the recovery group and remission group. Second, the IFS of the remission group was significantly higher compared to that of the non-remission group (area under the curve = 0.82; cut-off point = 70). Discussion & Conclusion The results from the present study show that pharmacotherapy following the guideline of the Japanese Society of Neuropsychopharmacology may contribute to achieving remission for patients with schizophrenia but may not be sufficient for recovery. Furthermore, we propose that an IFS of 70 may be an indicator for pharmacotherapy aimed at remission for patients with schizophrenia. References 1.Jaaskelainen, E., et al., A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull, 2013. 39(6): p. 1296-306.2. 2.Lally, J., et al., Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies. Br J Psychiatry, 2017. 211(6): p. 350-358.3. 3.Japanese Society of, N., Japanese Society of Neuropsychopharmacology: "Guideline for Pharmacological Therapy of Schizophrenia".Neuropsychopharmacol Rep, 2021. 41(3): p. 266-324.4. 4.Inada, K., et al., Development of individual fitness score for conformity of prescriptions to the "Guidelines For Pharmacological Therapy of Schizophrenia". Neuropsychopharmacol Rep, 2022. 42(4): p. 502-509.5. 5.Kodaka, F., et al., Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia. Int J Neuropsychopharmacol, 2023. 26(8): p. 557-565.6. 6.Liberman, R.P., et al., Operational criteria and factors related to recovery from schizophrenia. International Review of Psychiatry, 2002. 14(4): p. 256-272.7. 7.Andreasen, N.C., et al., Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry, 2005. 162(3): p. 441-9.8. 8.Overall, J.E. and D.R. Gorham, The Brief Psychiatric Rating Scale. Psychological Reports, 1962. 10(3): p. 799-812.9. 9.Addington, D., J. Addington, and E. Maticka-tyndale, Assessing Depression in Schizophrenia: The Calgary Depression Scale. British Journal of Psychiatry, 1993. 163(S22): p. 39-44.

We investigated the plasma tumor necrosis factor (TNF)-α levels between patients with schizophrenia remission and healthy controls, and the association between the plasma TNF-α levels and cognitive function and social function. This cross-sectional study included 48 patients with schizophrenia who fulfilled the remission criteria and 20 healthy controls. Plasma TNF-α levels were measured using the enzyme-linked immunosorbent assay, and cognitive function was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J). We measured social function using the Social Functioning Scale (SFS-J). The plasma TNF-α levels were significantly lower in the remission schizophrenia group (31.7 ± 27.4 ng/mL) compared to the heathy control group (55.1 ± 38.5 ng/mL) (P = 0.01). In contrast, no correlation was observed between the plasma levels of TNF-α and all BACS-J scores and all SFS-J scores in either group. This result suggests that plasma TNF-α levels may serve as a clinical biomarker of remission of schizophrenia and that the plasma TNF-α levels bore no association with cognitive function. Thus, TNF-α may have potential as a useful indicator of the therapeutic response in patients with schizophrenia.

AbstractBackgroundWhile drugs are sometimes taken during deliberate self‐harm (DSH), no study has attempted to analyze drugs in the blood of DSH patients and compare them with prescribed medications or other drugs. In this study, drugs were analyzed from the blood of DSH patients, and the detected, prescribed, and suspected drugs were documented.MethodsPatients who practiced DSH and were transferred to the emergency sites of Fukuoka University Hospital between April 2021 and September 2022 participated in the study. Psychiatrists assessed information such as the history of psychiatric treatment and recent methods of DSH, as well as prescribed drugs within 1 month of presenting to the hospital. Blood samples were analyzed using LC–MS/MS. Participants were divided into groups according to whether or not they were prescribed psychotropics within 1 month.ResultsFifty‐five patients were enrolled in the study. Forty had been prescribed psychotropics within 1 month of hospital admission. However, non‐prescribed drugs (NPD) were detected in 42 of the 55 participants (76%). The detection of NPD was significantly high among patients with overdose of medications and OTC drugs (p = 0.036), but NPD were also detected in patients who engaged in other methods (n = 14), and in patients without prescribed medication (n = 10).DiscussionThis is the first study focused on the drug analysis of blood from patients engaging in DSH. Approximately 80% of the DSH patients in this study had taken NPD, revealing a large discrepancy between prescribed medications and those detected in the blood.

Introduction: Psychiatric disorders are an important risk factor for suicide. The aim of this study was to compare the characteristics of suicide attempts between patients with schizophrenia and mood disorders in Japan. Methods: From 596 patients treated after a suicide attempt in the Emergency and Critical Care Center (ECCC), during a 15-year period (2006 and 2021), two groups of patients were separated, 196 patients with mood disorders (21% bipolar mood disorder and 79% monopolar depression) and 112 patients with schizophrenia, who were compared according to sex, age, method of suicide attempt, and history of psychiatric treatment. We conducted multivariable logistic regression on the schizophrenia group and the mood disorder group, using those diagnoses as the dependent variable and age, suicide attempt method, sex, and history of psychiatric treatment as explanatory variables. Results: Patients with schizophrenia are significantly younger (39.4 ± 13.3 vs. 47.8 ± 17.9; p < 0.001) and significantly more frequently (89.3% vs. 64.3%; p < 0.001) had a history of psychiatric treatment than patients with mood disorders. Violent suicide methods were significantly more often used in the group of patients with schizophrenia (65.2% vs. 50.5%; p = 0.017) than in the group of patients with mood disorders. Jumping from a height was significantly more frequent in the group of patients with schizophrenia (36.6% vs. 16.8%; p < 0.001) than in the group of patients with mood disorders, while hanging was significantly more frequent in the group of patients with mood disorders (12.8% vs. 2.7%; p = 0.003) than in the group of patients with schizophrenia. As a result of multivariable logistic regression, the history of psychiatric treatment (OR = 0.25; 95%CI: 0.11–0.54; p < 0.001) was associated with high odds of the diagnosis of schizophrenia, while the use of the hanging method (OR = 7.25; 95%CI: 1.48–43.6; p = 0.014) was associated with high odds of the diagnosis of mood disorder. Conclusions: Patients with schizophrenia and mood disorders are groups with a high risk of suicidal behavior. Suicide prevention measures should consist of the urgent need for screening and evaluation of mental disorders by primary health care services, as well as successful treatment, successful follow-up of patients after hospitalization, improvement of adherence to therapy, and monitoring of risk factors.

Treatment of bipolar disorder is prone to prolongation despite various treatments, including medication. The efficacy of exercise treatment (i.e., interventions involving physical exercise and sports intervention) for major depressive disorders has been reported for depressive symptoms, cognitive function, and sleep disturbances. However, its efficacy for bipolar disorder has yet to be established. We designed a randomized, controlled, double-blind clinical trial that includes 100 patients with bipolar disorder aged 20–65 years. This will be a cluster-randomized, two-group trial that will be conducted in ten psychiatric hospitals. The hospitals will be randomly assigned to an exercise intervention + treatment as usual (exercise) group or a placebo exercise intervention (stretching) + treatment as usual (control) group. Patients will be assessed using an extensive battery of clinical tests, physical parameters, sleep status, biological parameters (cytokines, neurotrophic factors), and genetic parameters (DNA and RNA) at baseline after a 6-week intervention period, at 10-week follow-up, and at 6-month follow-up. This innovative study may provide important evidence for the effectiveness of exercise in the treatment of bipolar depression based on clinical, biological, genetic, and physiological markers.

Major depressive disorder (MDD) is the most common psychiatric disorders. However, a biochemical marker has yet to be established for clinical purposes. It is proposed that lysophosphatidic acid (LPA, 1-acyl-2-sn-glycerol-3-phosphoate) plays some important roles in emotional regulation of experimental animals. Therefore, in this study, we measured LPA levels using enzyme-linked immunosorbent assays of cerebrospinal fluid (CSF) and plasma samples from patients with MDD. The participants were 52 patients and 49 normal healthy controls for CSF study, and 47 patients and 44 controls for plasma study. We used the Japanese version of the GRID Hamilton Depression Rating Scale (17-item version) for the assessment of depressive symptoms. We found no associations between LPA levels (CSF or plasma) and either diagnosis or severity of MDD, or with psychotropic medication. In conclusion, our data suggest that LPA levels likely would not serve as a practical biomarker of MDD.

Strategies to facilitate extinction of fear memory have attracted increasing attention for enhancing the effectiveness of exposure therapy for anxiety disorders. Previously, we demonstrated that systemic administration of a delta opioid receptor agonist, KNT-127, has clear anxiolytic-like effects in rats, without impairing memory. These observations led us to hypothesize that KNT-127 might be an appropriate therapeutic agent for anxiety disorders when combined with exposure therapy. In the present study, we demonstrate that KNT-127 (3 mg/kg) facilitates extinction learning of fear memory using the contextual fear conditioning test. As expected, a partial agonist at the glycine-binding site on the glutamatergic N-methyl-d-aspartate receptor, d-cycloserine (15 mg/kg), facilitated extinction learning of contextual fear in rats. In contrast, a benzodiazepine anxiolytic, diazepam (1 mg/kg), impaired the fear extinction learning. Interestingly, the facilitatory effect of KNT-127 on extinction learning was observed not only after a 10-min re-exposure, but also after a much shorter (2-min) re-exposure to the context, while d-cycloserine was ineffective at facilitating extinction when a short-duration exposure was given. Our findings may suggest that administration of a delta opioid receptor agonist might have therapeutic efficacy when combined with exposure therapy for treating a range of anxiety disorders.

It is suggested that lysophosphatidic acid (LPA) plays a key role in the pathophysiology of schizophrenia. In this study, we measured LPA levels by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) and plasma samples. The participants were 49 patients with schizophrenia and 49 normal healthy controls for CSF study, and 42 patients and 44 controls for plasma study. We found that LPA levels in the patients were not significantly different from those of controls in CSF (controls: 0.189 ± 0.077 µM, patients: 0.175 ± 0.067 µM; P = 0.318) and plasma samples (controls: 0.131 ± 0.067 µM, patients: 0.120 ± 0.075 µM; P = 0.465). On the other hand, CSF levels in medicated patients (0.162 ± 0.061 µM) were significantly lower than those observed in unmedicated patients (0.224 ± 0.067 µM, P = 0.038), suggesting that our findings could be masked by the influence of medication with antipsychotics. Interestingly, we detected significant negative correlation between PANSS scores and plasma LPA levels, especially in males and in unmedicated patients. Our result suggests that LPA levels in CSF and plasma samples would not serve as a diagnostic biomarker, but plasma levels could be used for symptomatic assessment of schizophrenia.

BACKGROUND:Clinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables.METHODS:We carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs).RESULTS:We found that relative to the HCs, the OCD patients showed significant decreased GM volume in the right hippocampus, and increased GM volume in the left precentral gyrus. 5-HTTLPR polymorphism in OCD patients had a statistical tendency of stronger effects on the right frontal pole than those in HCs.CONCLUSIONS:Our results showed that the neuroanatomical changes of specific GM regions could be endophenotypes of 5-HTTLPR polymorphism in OCD.