Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Novel α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator LT-102: A promising therapeutic agent for treating cognitive impairment associated with schizophrenia.

AIMS: We aimed to evaluate the potential of a novel selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator, LT-102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. METHODS: The activity of LT-102 was examined by Ca2+ influx assays and patch-clamp in rat primary hippocampal neurons. The structure of the complex was determined by X-ray crystallography. The selectivity of LT-102 was evaluated by hERG tail current recording and kinase-inhibition assays. The electrophysiological characterization of LT-102 was characterized by patch-clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. RESULTS: LT-102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT-102 facilitated long-term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine-induced mouse model. Additionally, LT-102 treatment increased the protein level of brain-derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. CONCLUSION: We conclude that LT-102 ameliorates cognitive impairments in a phencyclidine-induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS.

Transient Fever Response After ECT in a Patient with Catatonic Schizophrenia: A Case Report. / Katatonik Sizofreni Hastasinda EKT Sonrasi Ortaya Çikan Geçici Ates Yaniti: Olgu Sunumu.

Electroconvulsive therapy (ECT) is an effective and safe treatment method for many psychiatric disorders. In general medical practice, ECT may cause side effects as most other treatment methods do. Headache, myalgia, nausea, vomiting, confusion, anterograde amnesia are common side effects of electroconvulsive therapy. Fever; in addition to general medical conditions such as infection, malignancy, connective tissue diseases, drug treatments, malignant hyperthermia, convulsions, it can also occur due to conditions such as neuroleptic malignant syndrome (NMS), serotonin syndrome, catatonia, malignant catatonia, which are frequently encountered in psychiatry clinics. In the literature, transient fever response due to electroconvulsive therapy application have been described, albeit rarely. Although there are many proposed mechanisms for the emergence of a fever response, regardless of its cause, it is still not understood why some fever responses occur. In this article, we present the differential diagnosis of the fever response, possible causes, and the mechanisms that may reveal the secondary fever response to electroconvulsive therapy in a case with a diagnosis of catatonic schizophrenia, who developed a fever response during electroconvulsive therapy sessions and no fever response was observed at times other than electroconvulsive therapy sessions. In this case, postictal benign fever response associated with electroconvulsive therapy was considered after excluding other medical conditions that may cause a fever response after electroconvulsive therapy. Keywords: ECT, Fever, Catatonia, NMS.

Determinants and outcomes of health-promoting lifestyle among people with schizophrenia.

BACKGROUND: Healthy lifestyle is an important protective factor of developing cardiovascular disease in people with schizophrenia. However, little is known about the determinants of lifestyle and its contribution to metabolic syndrome. This study aimed to explore the influencing factors of health-promoting lifestyle (HPL) and its association with metabolic syndrome among people with schizophrenia. METHODS: A cross-sectional study was conducted in twenty-two primary health centers of Guangzhou, China between December 2022 and April 2023. A total of 538 patients with schizophrenia were recruited through convenience sampling. Self-administered scales, questionnaires, and clinical data were collected. Scales and questionnaires included social-demographic information, Health-Promoting Lifestyles Profile (HPLP-C), UCLA Loneliness Scale (ULS), and International Physical Activity Questionnaire-Short Form (IPAQ-SF). Cluster analyses were used to divide participants into two groups based on the distribution characteristics of HPLP-C scores. Logistic regression models were used to identify factors associated with HPL and the association between HPL and metabolic syndrome. RESULTS: There were 271 participants in the high HPL group and 267 participants in the low HPL group. Logistic regression analysis revealed that loneliness posed a risk factor for high HPL, while high education and moderate-vigorous physical activity served as protective factors for high HPL. Low HPL was a risk factor for the prevalence of metabolic syndrome. CONCLUSIONS: Promotion of high education literacy and a physically active lifestyle should be priority targets in the health management of schizophrenia. Primary healthcare providers can play a pivotal role in assisting patients to mitigate metabolic syndrome by reinforcing healthy lifestyle strategies.

The effect of exercise on cognition and clinical symptoms of patients with schizophrenia: A systematic review of randomized controlled trial.

Physical activity has been viewed as a potential non-pharmacological therapeutic strategy to improve the clinical symptoms and neurocognitive deficits in patients with schizophrenia. However, there are various types of physical activities, and different exercise prescriptions might produce inconsistent benefits. Thus, this study aimed to conduct a systematic review of exercise interventions for patients with schizophrenia, clarifying the benefits of these interventions on cognitive function and clinical symptoms. This review encompasses six electronic databases, with inclusion criteria including randomized controlled trial designs, participants with schizophrenia, and a comprehensive exercise intervention program. Twenty-seven studies met the inclusion criteria, incorporating data from 1549 patients with schizophrenia. The results highlight that when comparing the exercise intervention group to the non-intervention control group, patients with schizophrenia showed significant improvement in negative symptoms. Structured exercise interventions can help improve the negative symptoms of schizophrenia, filling the gaps where medication falls short. Regarding functional outcomes, exercise interventions aid in enhancing the overall functionality (psychological, social, occupational) of individuals with schizophrenia. The improvement is largely tied to the boost in physical fitness that exercise provides. Based on current findings, exercise interventions assist in enhancing cognitive function in patients with schizophrenia. Notably, significant improvements are observed in higher-order cognitive functions, including processing speed, attention, and working memory. It is recommended to engage in moderate-intensity exercises at least three times a week, with each session lasting a minimum of 30min. Well-structured exercise interventions contribute to enhancing the negative symptoms and cognitive functions in patients with schizophrenia.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Assessment of sarcopenic obesity as a predictor of pneumonia in patients with stable schizophrenia-A prospective study.

OBJECTIVE: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recently released the first international consensus on the diagnostic criteria for Sarcopenic obesity (SO). The present study aimed to explore the ability of SO to predict the risk of pneumonia in patients with stable schizophrenia. METHODS: This was a prospective study involving hospitalized patients with schizophrenia aged ≥50 years from two mental health centers in western China. Baseline patient data were collected from September 1 to September 30, 2020. Follow-up data on pneumonia were collected from October 2020 to October 2022. The diagnosis of SO was based on the ESPEN/EASO criteria. Patients were assessed for handgrip strength (HGS), skeletal muscle mass/weight (SMM/W), and fat mass percentage (FM%). Logistic regression analysis was used to explore the effect of SO on the risk of pneumonia in patients with stable schizophrenia. RESULTS: A total of 320 patients with stable schizophrenia were included. Of these, 74 (23.13%) were diagnosed with SO, while 117 (36.56%) developed pneumonia. Compared with patients in the non-low HGS, non-low HGS + non-low SMM/W (or non-low HGS + low SMM/W or low HGS + non-low SMM/W) and non-SO groups, the proportions of patients with pneumonia in the low HGS (42.3% vs. 25.9%, p = 0.004), low HGS + low SMM/W (45.3% vs. 33.3%, p = 0.048), and SO (47.3% vs. 33.3%, p = 0.029) groups, respectively, were higher. However, there was no difference in the proportion of patients with pneumonia in the low SMM/W group and the obese group compared with the non-low SMM/W and non-obese groups. Further logistic regression analysis after adjustment for potential influencing factors showed that compared with the non-low HGS group, patients in the low HGS group had a higher risk of pneumonia (OR = 1.892, 95%CI: 1.096-3.264). CONCLUSION: SO defined according to the ESPEN/EASO criteria was not found to be significantly associated with the development of pneumonia in patients with stable schizophrenia. Further verification of these results is needed with larger sample sizes and the establishment of a cutoff value for this population.

Association between degree centrality and neurocognitive impairments in patients with Schizophrenia: A Longitudinal rs-fMRI Study.

BACKGROUND: Evidence indicates that patients with schizophrenia (SZ) experience significant changes in their functional connectivity during antipsychotic treatment. Despite previous reports of changes in brain network degree centrality (DC) in patients with schizophrenia, the relationship between brain DC changes and neurocognitive improvement in patients with SZ after antipsychotic treatment remains elusive. METHODS: A total of 74 patients with acute episodes of chronic SZ and 53 age- and sex-matched healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS), Symbol Digit Modalities Test, digital span test (DST), and verbal fluency test were used to evaluate the clinical symptoms and cognitive performance of the patients with SZ. Patients with SZ were treated with antipsychotics for six weeks starting at baseline and underwent MRI and clinical interviews at baseline and after six weeks, respectively. We then divided the patients with SZ into responding (RS) and non-responding (NRS) groups based on the PANSS scores (reduction rate of PANSS ≥50%). DC was calculated and analyzed to determine its correlation with clinical symptoms and cognitive performance. RESULTS: After antipsychotic treatment, the patients with SZ showed significant improvements in clinical symptoms, semantic fluency performance. Correlation analysis revealed that the degree of DC increase in the left anterior inferior parietal lobe (aIPL) after treatment was negatively correlated with changes in the excitement score (r = -0.256, p = 0.048, adjusted p = 0.080), but this correlation failed the multiple test correction. Patients with SZ showed a significant negative correlation between DC values in the left aIPL and DST scores after treatment, which was not observed at the baseline (r = -0.359, p = 0.005, adjusted p = 0.047). In addition, we did not find a significant difference in DC between the RS and NRS groups, neither at baseline nor after treatment. CONCLUSIONS: The results suggested that DC changes in patients with SZ after antipsychotic treatment are correlated with neurocognitive performance. Our findings provide new insights into the neuropathological mechanisms underlying antipsychotic treatment of SZ.

Characterizing cognitive subtypes in schizophrenia using cortical curvature.

Cognitive deficits are a core symptom of schizophrenia, but research on their neural underpinnings has been challenged by the heterogeneity in deficits' severity among patients. Here, we address this issue by combining logistic regression and random forest to classify two neuropsychological profiles of patients with high (HighCog) and low (LowCog) cognitive performance in two independent samples. We based our analysis on the cortical features grey matter volume (VOL), cortical thickness (CT), and mean curvature (MC) of N = 57 patients (discovery sample) and validated the classification in an independent sample (N = 52). We investigated which cortical feature would yield the best classification results and expected that the 10 most important features would include frontal and temporal brain regions. The model based on MC had the best performance with area under the curve (AUC) values of 76% and 73%, and identified fronto-temporal and occipital brain regions as the most important features for the classification. Moreover, subsequent comparison analyses could reveal significant differences in MC of single brain regions between the two cognitive profiles. The present study suggests MC as a promising neuroanatomical parameter for characterizing schizophrenia cognitive subtypes.

Changes in BDNF methylation patterns after cognitive remediation therapy in schizophrenia: A randomized and controlled trial.

Although cognitive remediation therapy (CRT) produces cognitive benefits in schizophrenia, we do not yet understand whether molecular changes are associated with this cognitive improvement. A gene central to synaptic plasticity, the BDNF, has been proposed as one potential route. This study assesses whether BDNF methylation changes following CRT-produced cognitive improvement are detected. A randomized and controlled trial was performed with two groups (CRT, n = 40; TAU: Treatment as Usual, n = 20) on a sample of participants with schizophrenia. CRT was delivered by trained therapists using a web-based computerized program. Mixed Models, where the interaction of treatment (CRT, TAU) by time (T0: 0 weeks, T1: 16 weeks) was the main effect were used. Then, we tested the association between the treatment and methylation changes in three CpG islands of the BDNF gene. CRT group showed significant improvements in some cognitive domains. Between-groups differential changes in 5 CpG units over time were found, 4 in island 1 (CpG1.2, CpG1.7, CpG1.10, CpG1.17) and 1 in island 3 (CpG3.2). CRT group showed increases in methylation in CpG1.2, CpG1.7 and decreases in pG1.10, CpG1.17, and CpG3.2. Differences in the degree of methylation were associated with changes in Speed of Processing, Working Memory, and Verbal Learning within the CRT group. Those findings provide new data on the relationship between cognitive improvement and changes in peripheral methylation levels of BDNF gene, a key factor involved in neuroplasticity regulation. Trial Registration: NCT04278027.

Hemorrhoidal disease and its genetic association with depression, bipolar disorder, anxiety disorders, and schizophrenia: a bidirectional mendelian randomization study.

BACKGROUND: Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored their correlation, and these studies are often subject to reverse causality and residual confounding. We conducted a Mendelian randomization (MR) analysis to comprehensively investigate the association between several mental illnesses and hemorrhoidal disease. METHODS: Genetic associations for four psychiatric disorders and hemorrhoidal disease were obtained from large consortia, the FinnGen study, and the UK Biobank. Genetic variants associated with depression, bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease at the genome-wide significance level were selected as instrumental variables. Screening for potential confounders in genetic instrumental variables using PhenoScanner V2. Bidirectional MR estimates were employed to assess the effects of four psychiatric disorders on hemorrhoidal disease. RESULTS: Our analysis revealed a significant association between genetically predicted depression and the risk of hemorrhoidal disease (IVW, OR=1.20,95% CI=1.09 to 1.33, P <0.001). We found no evidence of associations between bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease. Inverse MR analysis provided evidence for a significant association between genetically predicted hemorrhoidal disease and depression (IVW, OR=1.07,95% CI=1.04 to 1.11, P <0.001). CONCLUSIONS: This study offers MR evidence supporting a bidirectional causal relationship between depression and hemorrhoidal disease.

[Associations between components of metabolic syndrome and cognitive impairment in patients with schizophrenia]. / Svyazi mezhdu komponentami metabolicheskogo sindroma i kognitivnymi narusheniyami u bol'nykh shizofreniei.

OBJECTIVE: To study the relationship between the individual components of the metabolic syndrome and cognitive dysfunction in patients with schizophrenia. MATERIAL AND METHODS: A total of 133 patients with schizophrenia were examined. To assess cognitive functioning, the Brief Assessment of Cognition in Schizophrenia (BACS) was used. The components of the metabolic syndrome were determined in accordance with the criteria of the International Diabetes Federation. RESULTS: Hyperglycemia in patients with schizophrenia led to a decrease in cognitive functioning in two domains: verbal fluency (ß=-10.67; p=0.019) and attention stability (ß=-9.519; p=0.043). Abdominal obesity was associated with lower indicators of executive functions (ß=-8.856; p=0.026). CONCLUSION: It is assumed that drug treatment of some components of the metabolic syndrome may affect cognitive functions in patients with schizophrenia.

Taste dysfunction as a predictor of depression in schizophrenia: A systematic review and meta-analysis.

OBJECTIVE: This study aims to investigate the relationship between taste dysfunction and depression among patients with schizophrenia, to achieve early detection of depression in clinical practice. METHODS: Following PRISMA guidance, a comprehensive literature search was conducted globally, covering papers published from 1961 to June 2023. A total of 17 manuscripts were selected through meta-analysis and sensitivity analysis after examining available materials from seven databases to determine the correlation between depression and taste dysfunction. RESULTS: The comparison of the 17 selected manuscripts revealed that individuals with gustatory dysfunction may be more likely to experience depressive symptoms (SMD, 0.51, 95% CI, 0.08 to 0.93, p = 0.02). Depression is associated with taste dysfunction in certain aspects, as indicated by the pleasantness ratings of sucrose solutions (SMD, -0.53, 95% confidence interval [CI] -1.11 to 0.05, p = 0.08), gustatory identification ability (SMD, 0.96, 95% CI, 0.03 to 1.89, p = 0.04), and the perception threshold of sweet taste (MD, 0.80, 95% CI, 0.79 to 0.81, p < 0.00001). CONCLUSIONS: Due to variations in the methods, designs, and selection criteria employed in the included studies, it is necessary to establish a feasible framework. Future research using detailed and targeted approaches can provide clearer and more unified conclusions on the relationship between taste dysfunction and depression. Moreover, further high-quality research is needed to obtain clearer conclusions and explore the potential of taste dysfunction as an effective tool for early screening of depression. TRIAL REGISTRATION: This review has been registered in the PROSPERO on April 2022 with the identifier CRD42023400172.

Immersive virtual reality in the treatment of auditory hallucinations: A PRISMA scoping review.

BACKGROUND: A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging. OBJECTIVE: The aim of this scoping review is to provide an overview of clinical trials utilizing VR in the treatment of AH and to document knowledge gaps in the literature. METHODS: PubMed, Cochrane Library, and Embase were searched for studies reporting on the use of VR to target AH. RESULTS: 16 papers were included in this PRISMA scoping review (ScR). In most studies VR therapy (VRT) was employed to ameliorate treatment resistant AVH in schizophrenia spectrum disorders. Only two studies included patients with a diagnosis of affective disorders. The VRT was carried out with the use of an avatar to represent the patient's most dominant voice. DISCUSSION: The research field employing VR to treat AH is promising but still in its infancy. Results from larger randomized clinical trials are needed to establish substantial evidence of therapy effectiveness. Additionally, the knowledge base would benefit from more profound qualitative data exploring views of patients and therapists.

Employing graph attention networks to decode psycho-metabolic interactions in Schizophrenia.

Schizophrenia is a severe mental disorder characterized by intricate and underexplored interactions between psychological symptoms and metabolic health, presenting challenges in understanding the disease mechanisms and designing effective treatment strategies. To delve deeply into the complex interactions between mental and metabolic health in patients with schizophrenia, this study constructed a psycho-metabolic interaction network and optimized the Graph Attention Network (GAT). This approach reveals complex data patterns that traditional statistical analyses fail to capture. The results show that weight management and medication management play a central role in the interplay between psychiatric disorders and metabolic health. Furthermore, additional analysis revealed significant correlations between the history of psychiatric symptoms and physical health indicators, as well as the key roles of biochemical markers(e.g., triglycerides and low-density lipoprotein cholesterol), which have not been sufficiently emphasized in previous studies. This highlights the importance of medication management approaches, weight management, psychological treatment, and biomarker monitoring in comprehensive treatment and underscores the significance of the biopsychosocial model. This study is the first to utilize a GNN to explore the interactions between schizophrenia symptoms and metabolic features, providing new insights into understanding psychiatric disorders and guiding the development of more comprehensive treatment strategies for schizophrenia.

Exploring the cognitive profiles related to unimodal auditory versus multisensory hallucinations in schizophrenia-spectrum disorders.

INTRODUCTION: Hallucinations can be experienced across multiple sensory modalities, but psychiatric studies investigating the cognitive mechanisms of hallucinations have been somewhat restricted to the auditory domain. This study explored the cognitive profiles of individuals experiencing multisensory hallucinations (MH) in schizophrenia-spectrum disorders (SSD) and compared these to those experiencing unimodal auditory hallucinations (AH) or no hallucinations (NH). METHODS: Participants included SSD patients (n = 119) stratified by current hallucination status (NH, AH, MH) and nonclinical controls (NCs; n = 113). Group performance was compared across several cognitive domains: speed of processing, attention, working memory, verbal learning, visual learning, reasoning and problem-solving, social cognition, and inhibition. RESULTS: The clinical groups performed worse than NCs but differences between the clinical groups were not evident across most cognitive domains. Exploratory analyses revealed that the MH group was more impaired on the visual learning task compared to the NH (but not AH) group. CONCLUSIONS: Preliminary results suggest that impaired visual learning may be related to MH. This could be attributed to the presence of visual hallucinations (VH), or greater psychopathology, in this group. However, replication is needed, as well as the investigation of other potential cognitive mechanisms of MH.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder.

Importance: The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others.Observations: A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development.Conclusions and Relevance: Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder.Prim Care Companion CNS Disord 2024;26(1):23nr03596. Author affiliations are listed at the end of this article.

Efficacy and Safety of Valbenazine in Japanese Patients With Tardive Dyskinesia and Schizophrenia/Schizoaffective Disorder or Bipolar Disorder/Depressive Disorder: Primary Results and Post Hoc Analyses of the J-KINECT Study.

PURPOSE: This post hoc analysis investigated whether a patient's underlying psychiatric disease (schizophrenia/schizoaffective disorder [SCHZ] or bipolar disorder/depressive disorder [MOOD]) influenced the efficacy or safety of valbenazine for tardive dyskinesia (TD) in an Asian population. METHODS: We analyzed data from J-KINECT, a multicenter, phase II/III, randomized, double-blind study, which consisted of a 6-week placebo-controlled period followed by a 42-week extension where Japanese patients with TD received once-daily 40- or 80-mg valbenazine. We compared the change from baseline in Abnormal Involuntary Movement Scale total score and Clinical Global Impression of TD score between patients with SCHZ and those with MOOD, and incidence of treatment-emergent adverse events. RESULTS: Of 256 patients included in the placebo-controlled period, 211 continued to the long-term extension. The mean change from baseline in Abnormal Involuntary Movement Scale total score at week 6 (95% confidence interval) was -1.8 (-3.2 to -0.5) and -3.3 (-4.7 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (SCHZ group), and -2.4 (-3.9 to -0.9) and -3.5 (-5.1 to -1.9) in the valbenazine 40- and 80-mg groups, respectively (MOOD group), demonstrating improvement at either dose level over placebo, regardless of the underlying disease. These results were maintained to week 48, and improvements of Clinical Global Impression of TD scores were similar. There were no notable differences in the incidence of serious or fatal treatment-emergent adverse events by underlying disease; differences in the incidence of worsening schizophrenia and depression were attributed to underlying disease progression. CONCLUSIONS: Safety and efficacy of long-term valbenazine therapy for TD did not vary according to underlying psychiatric disease.