Need for education of psychiatric evaluation of offenders with mental disorders: A questionnaire survey for Japanese designated psychiatrists.

BACKGROUND: The management of offenders with mental disorders has been a significant concern in forensic psychiatry. In Japan, the introduction of the Medical Treatment and Supervision Act in 2005 addressed the issue. However, numerous psychiatric patients at risk of violence still find themselves subject to the administrative involuntary hospitalization (AIH) scheme, which lacks clarity and updated standards. AIM: To explore current as well as optimized learning strategies for risk assessment in AIH decision making. METHODS: We conducted a questionnaire survey among designated psychiatrists to explore their experiences and expectations regarding training methods for psychiatric assessments of offenders with mental disorders. RESULTS: The findings of this study's survey suggest a prevalent reliance on traditional learning approaches such as oral education and on-the-job training. CONCLUSION: This underscores the pressing need for structured training protocols in AIH consultations. Moreover, feedback derived from inpatient treatment experiences is identified as a crucial element for enhancing risk assessment skills.

Cerebellar and Occipital Alterations in Brain Perfusion in a Patient With Post-acute COVID-19 Encephalopathy Misdiagnosed As Primary Psychotic Disorder.

We describe the case of an unvaccinated 21-year-old Japanese male who experienced psychotic symptoms attributed to encephalopathy, known as post-acute COVID-19 syndrome (PACS). One week after his discharge following the remission of a SARS-CoV-2 infection, he experienced hyperactive delirium and unexpected movements of his limbs. As COVID-19-associated encephalopathy was suspected as a cause of the psychotic symptoms, he was admitted to the Department of Neurology. He received antiviral and steroid pulse therapy, but his psychiatric symptoms did not improve completely. Consequently, he was admitted to our psychiatric ward with a diagnosis of a primary psychotic disorder. Although he did not take psychopharmacotherapy, he gradually achieved a remission of psychiatric symptoms. At three months post-SARS-CoV-2 infection, single-photon emission computed tomography (SPECT) revealed hypoperfusion in the bilateral cerebellar dentate nuclei and occipital lobes. However, no abnormal findings were observed on fluorine-18 fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) at six months after the infection. This case indicates that (1) brain perfusion SPECT can be effective for detecting functional alterations in post-acute COVID-19-associated encephalopathy, and (2) it is necessary to carefully monitor patients' progress instead of quickly diagnosing a primary psychotic disorder.

Reduction of claudin-5 and aquaporin-4 in the rat hippocampal CA-1 and CA-3 regions of a learned helplessness model of depression.

BACKGROUND: Although findings from both animal and clinical research indicate that the blood-brain barrier (BBB) contributes to the pathogenesis of various psychiatric disorders (including depression), the underlying mechanisms are unknown. We investigated the levels of the tight-junction proteins claudin-5 and aquaporin-4 (AQP-4) in astrocytes of learned helplessness (LH) rats (an animal model of depression) and non-LH rats (a model of resilience). METHODS: We administered inescapable mild electric shock to rats and then identified the LH and non-LH rats by a post-shock test. The expressions of claudin-5 and AQP-4 in several brain regions of the LH and non-LH rats were then evaluated by a western blot analysis. RESULTS: The levels of both claudin-5 and AQP-4 in the CA-1 and CA-3 hippocampal areas of the LH group were significantly lower than those of the control group, whereas those of the non-LH rats were not significantly different from those of the control and LH rats. CONCLUSIONS: These results suggest that LH rats but not non-LH rats experienced down-regulations of claudin-5 and AQP-4 in the CA-1 and CA-3. It is possible that a region-specific modulation of claudin-5 and AQP-4 is involved in the mechanisms of vulnerability but not resilience in depression.

A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists.

STUDY OBJECTIVES: Although novel hypnotics have recently emerged, there are currently no data comparing the clinical potency of benzodiazepine receptor agonists (BZRAs) and novel hypnotics, or the effectiveness of different methods of switching between them. This study examined how novel hypnotics might help reduce BZRA use in real-world practice. METHODS: 289 patients with psychiatric disorders who took BZRAs for over 1 year before switching to either of 2 dual-orexin receptor antagonists (DORAs; suvorexant [SUV] or lemborexant [LEM]) or a melatonin receptor agonist (ramelteon [RMT]) were enrolled. We collected data on BZRAs at baseline and 3 months after commencement of SUV/LEM/RMT. RESULTS: Significant reductions in BZRAs were observed for all 3 agents: -4.10, -2.80, and -1.65 mg in diazepam-equivalent doses in the SUV, LEM, and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F = 15.053, P < .001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F = 4.337, P = .043). The switching success rate did not differ among the switching methods for any of the hypnotics. CONCLUSIONS: The reduction rate of BZRAs achieved by the switch fell into their equivalent-potency range estimated from clinical trials. The results suggest that DORAs can replace approximately 1 tablet of a BZRA. The difference in dose reduction between DORAs and RMT reflected the greater sleeping potency of the DORAs, whereas that between SUV and LEM might have reflected patient backgrounds: patients taking LEM may have been more strongly dependent on BZRAs. CITATION: Tachibana M, Kanahara N, Oda Y, Hasegawa T, Kimura A, Iyo M. A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists. J Clin Sleep Med. 2024;20(4):603-613.

Current practice for clozapine-induced leukopenia in Japanese psychiatric hospitals: A nationwide survey.

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. In Japan, its use requires management by a blood monitoring system called the Clozaril Patient Monitoring Service (CPMS) for the early detection of serious side effects such as agranulocytosis, which is extremely rare. Monitoring services vary among the clozapine suppliers in different countries. Additionally, Japanese patients can be started on clozapine treatment exclusively through an 18-week inpatient admission at a psychiatric hospital capable of coordinating with a hematologist. One reported reason for the lack of widespread clozapine use in Japan is the difficulty in establishing collaboration with hematologists when agranulocytosis/leukopenia occurs. Hence, we conducted a nationwide web-based survey of CPMS-registered psychiatric facilities in Japan to determine the status of collaboration with hematology departments. Valid responses were received from the psychiatrists responsible for prescribing clozapine at 203 of the 547 facilities (response rate: 37.1 %). The largest number of psychiatric facilities (61 %) collaborated with hematologists at another facility with a psychiatry department, while psychiatrists in 32 % of the facilities worked with hematologists at their own facilities. Most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist. The actual workload of hematologists was limited, and the patients might experience the burden of repeated blood sampling. This study suggests that disseminating information regarding the status of collaborations with hematologists may promote the widespread use of clozapine in Japan. SHORT COMMENT FOR TWITTER: This study suggests that most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist.

A pilot trial of an online guided self-help cognitive behavioral therapy program for bulimia nervosa and binge eating disorder in Japanese patients.

BACKGROUND: The purpose of this study was to develop an internet-based Guided Self-Help CBT (iGSH-CBT) for Bulimia Nervosa (BN) / Binge Eating Disorder (BED) for Japanese patients and to test its feasibility. METHODS: A single-arm feasibility study. After baseline assessment, patients underwent a 16-week iGSH-CBT program, our Japanese adaption of the European-based Salut BN program. During the treatment period, weekly email support from trained counselors was provided. Evaluations were performed at baseline, after 8 weeks, at the end of the 16-week intervention, and at 2 months after treatment had ended. The primary outcome measure was the change in the weekly frequency of objective binging. Secondary outcomes were the change in the weekly frequency of objective purge episodes, responses on self-report questionnaires of the frequencies of binging and purging, psychopathological characteristics of eating disorders found on BITE, EDE-Q, EDI-2, HADS and EQ-5D, measurements of motivation, and completion of intervention (vs. dropout). RESULTS: Participants were 9 female outpatients with BN (n = 5) or BED (n = 4), of whom 8 (88.9%) attended the assessment at the end of the 16-week intervention. Mean age was 28 years (SD = 7.9). Percent change of the weekly frequency of objective binging was -4.40%, and at the end of the 16-week intervention 25% of the participants had achieved symptom abstinence. CONCLUSIONS: No adverse events were observed during the treatment period and follow-up, and the implementation and operation of the program could be performed without any major problems, confirming the feasibility of iGSH-CBT for BN and BED for Japanese patients. Although no significant change was observed in the weekly frequency of objective binging, the abstinence rate from bulimic behaviors of those who completed the assessments was 25.0% at the end of treatment, and the drop-out rate was 11.1%. iGSH-CBT may be an acceptable and possibly even a preferred method of CBT delivery for Japanese patients with BN or BED, and our Japanese adaptation of Salut BN seems feasible. TRIAL REGISTRATION: UMIN, UMIN000031962. Registered 1 April 2018 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000036334.

Can brexpiprazole be switched safely in patients with schizophrenia and dopamine supersensitivity psychosis? A retrospective analysis in a real-world clinical practice.

BACKGROUND: Several studies have reported that a switch to the dopamine partial agonist (DPA) aripiprazole (ARP), especially when the switch is abrupt, is likely to fail and sometimes worsen psychosis in schizophrenia patients already under high-dose antipsychotic treatment. Such a switching failure is speculated to be related to be the dopamine supersensitivity state. The risks of switching to the DPA brexpiprazole (BREX) have not been reported. AIMS AND METHODS: We retrospectively analyzed the cases of 106 patients with schizophrenia to identify any factors related to the success or failure of switching to BREX. RESULTS: The comparison between the patients with dopamine supersensitivity psychosis (n = 44) and those without (n = 62) revealed no significant difference in the switching failure judged at the sixth week. A comparison of the patients with successful switching (n = 80) and those who failed (n = 26) revealed that patients with treatment-resistant schizophrenia (TRS) were significantly more likely to fail. A logistic regression analysis also revealed that patients with past failure of switching to ARP are likely to succeed in switching to BREX. The 2-year follow-up of the patients with successful switching to BREX suggested that the patients who were treated with BREX, even temporarily, experienced some improvement in their Global Assessment of Functioning and Clinical Global Impression-Severity scores. CONCLUSIONS: Overall, the results indicate that patients with schizophrenia can be switched more safely to BREX compared to ARP. However, the failure of switching to BREX could be higher in patients with TRS, and thus, starting BREX treatment in refractory patients warrants careful monitoring.

An exploratory database study of factors influencing the continuation of brexpiprazole treatment (prescription) in patients with schizophrenia using information from psychiatric electronic medical records processed with natural language processing.

Using natural language processing (NLP) technology to analyze and organize textual information in psychiatric electronic medical records can identify undiscovered factors associated with treatment discontinuation. This study aimed to evaluate brexpiprazole treatment continuation rate and factors affecting brexpiprazole discontinuation using a database that employs the MENTAT® system with NLP technology. This retrospective observational study evaluated patients with schizophrenia who were newly initiated on brexpiprazole (April 18, 2018-May 15, 2020). The first prescriptions of brexpiprazole were followed up for 180 days. Factors associated with brexpiprazole discontinuation were assessed using structured and unstructured patient data (April 18, 2017-December 31, 2020). The analysis population comprised 515 patients; mean (standard deviation) age of patients was 48.0 (15.3) years, and 47.8 % were male. Using Kaplan-Meier analysis, the cumulative brexpiprazole continuation rate at 180 days was 29 % (estimate: 0.29; 95 % confidence interval, 0.25-0.33). Univariate Cox proportional hazards analysis identified 16 variables independently associated with brexpiprazole discontinuation. Multivariate analysis identified eight variables associated with treatment discontinuation: variables with hazard ratio <1 were the presence of physical complications, longer hospitalization duration, and maximum chlorpromazine-equivalent dose of antipsychotics of >200 to ≤400 mg/day vs ≤200 mg/day in the past year; variables with hazard ratio >1 were previous electroconvulsive therapy, availability of key contact person information, a history of crime committed/reported, increase in brexpiprazole dose to 2 mg in >28 days, and appearance/worsening of symptoms other than positive symptoms. In conclusion, we identified potential new factors that may be associated with brexpiprazole discontinuation, which may improve the treatment strategy and continuation rate in patients with schizophrenia.

Efficacy of Asenapine in Drug-resistant Psychotic Patients with Dopamine Supersensitivity Psychosis: Two Cases.

Dopamine supersensitivity psychosis (DSP) is an unstable clinical condition observed in individuals with schizophrenia who have been treated with an antipsychotic medication at a high dosage and/or for a long period. An up-regulation of dopamine D2 receptors (DRD2) is thought to be involved in the essential pathology of DSP. An antipsychotic agent with both tight binding to DRD2 and a long half-life is generally effective for treating DSP, but a patient who meets the criteria of treatment-resistant schizophrenia sometimes needs treatment with clozapine. We report the case details of two patients whose DSP was not controlled with several antipsychotics but was successfully controlled with asenapine. Asenapine binds to a broad range of dopamine receptors and serotonin receptors, and it is thus distinct from other atypical antipsychotics. The unique profile of asenapine may contribute to the control of severe DSP symptoms in individuals with schizophrenia.

Dopamine supersensitivity psychosis and delay of clozapine treatment in patients with treatment-resistant schizophrenia.

Both the underutilization of clozapine and treatment resistance of patients to clozapine are serious problems worldwide. Identifying clinical markers predicting response to clozapine would help clinicians more effectively utilize clozapine treatment. The present study retrospectively assessed dopamine supersensitivity psychosis (DSP) in addition to other measures such as age at disease onset and delay of clozapine introduction for a total of 47 treatment-resistant schizophrenia (TRS) patients. The response to clozapine was judged with CGI-C at 1 and 2 years from clozapine introduction. Results revealed that the DSP group tended to have a longer delay between designation of TRS and introduction of clozapine and continued to have slightly more severe psychopathology after treatment with clozapine, showing only slight improvement. The logistic regression analysis showed that the age at disease onset was the only significant indicator, predicting responsiveness to clozapine: patients with an onset age <20 years had a significantly better response to clozapine than patients with an onset age ≥20 years. The present study suggests that DSP might be related to a longer delay in clozapine introduction and the persistence of refractory symptoms despite clozapine treatment, whereas early age of disease onset might be related to a better response to clozapine.

Effectiveness of Brexpiprazole in a Patient With Bipolar Disorder and Comorbid Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia: A Case Report.

Although the symptoms of persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) can have negative impacts on patients' lives, it is an under-recognized clinical entity. We describe the case of a 61-year-old Japanese female who suffered simultaneously from bipolar disorder and PGAD/GPD. She developed PGAD/GPD approx. 10 years after being diagnosed with bipolar disorder. Despite 20 years of various drug treatments, her bipolar disorder and PGAD/GPD symptoms showed little improvement. She had also undergone multiple sessions of cognitive behavioral therapy (CBT) and mindfulness, nerve block, botulinum toxin injections, and laser treatment for PGAD/GPD. Her PGAD/GPD symptoms remained with no significant improvement, and her bipolar disorder symptoms had also not responded well to medication. With the administration of brexpiprazole, she achieved remission of her bipolar disorder. Her PGAD/GPD symptoms also eventually improved. When PGAD/GPD is comorbid with bipolar disorder, the improvement of bipolar disorder may also lead to relief of PGAD/GPD symptoms. This case reveals that brexpiprazole, which has a unique profile, may be effective for PGAD/GPD.

Association of SLC6A3 variants with treatment-resistant schizophrenia: a genetic association study of dopamine-related genes in schizophrenia.

Background: Most genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways. Patients and methods: To examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489). Results: The distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology. Conclusion: The overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS.

Long-Term Treatment With Long-Acting Injectable Antipsychotic in Schizophrenia Patients With and Without Dopamine Supersensitivity Psychosis: A 6-Year Retrospective Comparative Study.

BACKGROUND: Dopamine supersensitivity psychosis (DSP) is an unstable psychotic state in patients with schizophrenia due to an upregulation of dopamine D2 receptors induced by antipsychotic medication. Long-acting antipsychotic injectable (LAI) could be advantageous for controlling the dopamine supersensitivity state, but it is not known if long-term treatment with LAI might ultimately lead to development or exacerbation of DSP. METHODS: The present study included 58 patients who had been treated with LAI for at least 3 years, with medical records for the 3 years before its introduction. Those records were used to classify patients as having DSP (n = 30, DSP group) or not (n = 28, non-DSP group). The effects of LAI treatments on the clinical course during the 3 years after the LAI introduction were compared between the 2 groups. RESULTS: Both groups demonstrated significant decreases in antipsychotic dosage (combined LAI and oral antipsychotics) and a significant improvement measured by clinical global impression-improvement. These indicators did not differ between them, suggesting similar efficacy of LAI for both groups. On average, the DSP group was treated with a higher dose of antipsychotics (1004.8 mg) before the LAI introduction compared with the non-DSP group but reduced them to within the standard dose range (662.0 mg) after the introduction of LAI. CONCLUSIONS: Our results indicated the effectiveness of LAI treatment for at least 3 years for patients with DSP, suggesting that this treatment strategy is unlikely to worsen DSP. The efficacy might be explained by the large decrease in the total antipsychotic dose with the introduction of LAI.

The cortical silent period in schizophrenia: A systematic review and meta-analysis focusing on disease stage and antipsychotic medication.

BACKGROUND: Although numerous studies reported some changes of cortical silent period (CSP), an indicator of gamma-aminobutyric acid (GABA) function in central nervous system, in schizophrenia patients, it has been unknown how the disease stage and antipsychotic medication affect CSP values. METHODS: The present study conducted a systematic review of previous literature comparing CSP between schizophrenia patients and healthy subjects, and then performed meta-analysis on the effects of (1) the disease stage and (2) antipsychotics on CSP. RESULTS: (1) In the comparison of the disease stage comprising a total of 17 reports, there was no significant difference in CSP between patients under drug-naïve first-episode psychoses and healthy controls, or between patients with antipsychotic medication and healthy controls. (2) In the comparison of the antipsychotic class, patients treated with clozapine were longer in CSP compared to healthy controls. Patients treated with olanzapine/quetiapine or with other type of antipsychotics were not different from healthy controls. Regarding other type of antipsychotics, the iteration analysis after leaving out one literature showed that patients were shorter in CSP than healthy controls. CONCLUSION: The results showed that clozapine seems to surely prolong CSP, indicating the enhancement of GABA transmission via GABAB receptors, suggesting the possible relationship between the CSP prolongation by clozapine and its high efficacy in psychopathology. The finding of shorter CSP in patients with other type of antipsychotics was distinct from clozapine/olanzapine/quetiapine, but was difficult to interpret since this group included a variety of transcranial magnetic stimulation (TMS) methodologies and patients' background.

Ifenprodil tartrate treatment of adolescents with post-traumatic stress disorder: A double-blind, placebo-controlled trial.

BACKGROUND: Several lines of evidence suggest that glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptor plays a role in certain behavioral manifestations common to Post-Traumatic Stress Disorder (PTSD). Ifenprodil tartrate is a neuroprotective agent that binds to the GluN2B subunit of the NMDA receptor. The aim of this study is to confirm whether ifenprodil tartrate is effective in the adolescent PTSD patients. METHODS: This is a randomized, double-blind, placebo-controlled trial. Ten adolescent (13 to 18 years old) PTSD patients were randomized into two arms: placebo (n = 4), 40 mg/day ifenprodil tartrate (n = 6) for 4 weeks. All of the patients were assessed by IES-R-J (Primary outcome measure), TSCC-J, CDRS-R, DSRS-C-J and CGI-I. RESULTS: A comparison of baseline IES-R-J total scores and 4-week end-point scores showed a mild trend of improvement (p = 0.0895) and the difference score was -9.314. A comparison of baseline scores and 2-week intermediate-point scores showed that IES-R-J hyperarousal subscores and TSCC-J subscores (dissociation subscores, sexual concerns subscores) improved significantly. A comparison of baseline TSCC-J sexual concerns subscores and 4-week end-point scores improved significantly. CONCLUSIONS: Our study may prove to be an short-term effective alternative safe treatment for adolescent patients with PTSD.

Narcolepsy-like symptoms triggered by lemborexant in the context of hyperactive delirium in a patient with bipolar depression: a case report.

Lemborexant is a dual orexin antagonist and is considered a safe and effective hypnotic. Dual orexin antagonists induce physiological sleep by blocking orexin receptors. Although the blockade of orexin signaling has triggered narcolepsy-like symptoms in rodents, there is currently no evidence of lemborexant inducing narcolepsy-like symptoms in humans. We describe the case of a 79-year-old Japanese woman with bipolar depression who experienced lemborexant-induced cataplexy and sleep attack. Her previous results on the Multiple Sleep Latency Test excluded the diagnosis of narcolepsy. She experienced narcolepsy-like symptoms on 2 occasions after she was administered lemborexant, in the context of hyperactive delirium, but not in a relaxed state. Her case suggests that lemborexant could trigger narcolepsy-like symptoms in patients with hyperactive delirium, even those with no history of narcolepsy. This case also emphasizes that clinicians must be very careful when they prescribe lemborexant to patients who experience hyperactive delirium. CITATION: Shibata S, Oda Y, Ohki N, et al. Narcolepsy-like symptoms triggered by lemborexant in the context of hyperactive delirium in a patient with bipolar depression: a case report. J Clin Sleep Med. 2022;18(5):1459-1462.

A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia.

BACKGROUND: GABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant schizophrenia (TRS) generally suffer from profound cognitive impairments in addition to severe positive symptoms, suggesting that GABA system dysfunction could be involved more closely in patients with TRS. METHODS AND RESULTS: In the present study, exome sequencing was conducted on fourteen TRS patients, whereby four SNPs were identified on GAD1, GABBR1 and GABBR2 genes. An association study for five SNPs including these 4 SNPs and rs3749034 on GAD1 as then performed among 357 patients with TRS, 682 non-TRS patients and 508 healthy controls (HC). The results revealed no significant differences in allelic and/or genetic distributions for any of the five SNPs. However, several subanalyses in comparisons between schizophrenia and HC groups, as well as between the three groups, showed nominal-level significance for rs3749034 on GAD1 and rs10985765/rs3750344 on GABBR2. In particular, in comparisons of female subjects, rigorous analysis for rs3749034 showed a statistical difference between the schizophrenia and HC groups and between the TRS and HC groups. CONCLUSIONS: Several positive results in subanalyses suggested that genetic vulnerability in the GABA system to schizophrenia or TRS could be affected by sex or sampling area, and overall, that rs3749034 on GAD1 and rs10985765 on GABBR2 could be related to TRS. In the present study, only a few SNPs were examined; it is possible that other important genetic variants in other regions of GABA-related genes were not captured in this preliminary study.

The effects of cumulative antipsychotic dose on brain structures in patients with schizophrenia: Observational study of multiple CT scans over a long-term clinical course.

Multiple lines of evidence indicate that antipsychotic agents could affect brain structures of schizophrenia patients. However, the effect of antipsychotic dosage or type on brain structure is uncertain. The present study retrospectively analyzed brain computed tomography (CT) images from a psychiatric hospital to examine the relationship between cumulative dose of antipsychotics and brain volume reduction in schizophrenia patients. A total of 43 patients with repeated relapse episode of psychosis were included and CT scans that were performed an average of 3.2 times per patient during nearly 13 years of follow-up were analyzed. The results revealed significant positive relationships of expansion of cerebrospinal fluid space with cumulative dosage of all antipsychotics and that of typical antipsychotics. Patients treated with antipsychotics including typical antipsychotics exhibited a greater volume reduction compared to patients treated with only atypical antipsychotics. The present study was one of the longest longitudinal studies examining the effects of antipsychotics on brain volume in schizophrenia patients. These results suggest a relation between cumulative lifetime antipsychotic dosage and progressive brain volume reduction in patients with schizophrenia. However, the effects of specific agent on brain structure are still uncertain, and more detailed analysis is needed.

Reliability and validity of the Japanese version of the 4A's Test for delirium screening in the elderly patient.

Although many screening tools for delirium are available, delirium is still occasionally overlooked or misdiagnosed. One of the reasons for this is the lack of brief screening tools that do not require specialized training to use. The 4 'A's test (the 4AT) is a validated screening tool for delirium that can be administered in a very short time without specialized training. Herein, we evaluated the reliability and validity of the Japanese version of the 4AT (the 4AT-J). A total of 150 patients aged ≥ 65 years were enrolled. Their demographics and clinical characteristics were obtained within 24 hr of their hospitalization. On each patient's high-risk day of developing delirium, the 4AT-J was administered by a nurse, and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-Ⅴ) and the Japanese version of Delirium Rating Scale-Revised-98 (DRS-98-J) were administered by a psychiatrist. Our analyses revealed that when a cut-off score of 4, the 4AT-J showed high sensitivity and specificity. The Cronbach's α-coefficient was similar to that of the original version. A receiver operating curve analysis showed sufficient power of the 4AT-J to discriminate delirium. The 4AT-J showed adequate reliability and validity for delirium screening in elderly patients.