Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

BACKGROUND: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. METHODS: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. RESULTS: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. CONCLUSIONS: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.

Vasopressin (VP)-regulated aquaporin-2 (AQP2) trafficking between cytoplasmic vesicles and the plasma membrane of kidney principal cells is essential for water homeostasis. VP affects AQP2 phosphorylation at several serine residues in the COOH-terminus; among them, serine 256 (S256) appears to be a major regulator of AQP2 trafficking. Mutation of this serine to aspartic acid, which mimics phosphorylation, induces constitutive membrane expression of AQP2. However, the intracellular location(s) at which S256 phosphorylation occurs remains elusive. Here, we used strategies to block AQP2 trafficking at different cellular locations in LLC-PK1 cells and monitored VP-stimulated phosphorylation of S256 at these sites by immunofluorescence and Western blot analysis with phospho-specific antibodies. Using methyl-ß-cyclodextrin, cold block or bafilomycin, and taxol, we blocked AQP2 at the plasma membrane, in the perinuclear trans-Golgi network, and in scattered cytoplasmic vesicles, respectively. Regardless of its cellular location, VP induced a significant increase in S256 phosphorylation, and this effect was not dependent on a functional microtubule cytoskeleton. To further investigate whether protein kinase A (PKA) was responsible for S256 phosphorylation in these cellular compartments, we created PKA-null cells and blocked AQP2 trafficking using the same procedures. We found that S256 phosphorylation was no longer increased compared with baseline, regardless of AQP2 localization. Taken together, our data indicate that AQP2 S256 phosphorylation can occur at the plasma membrane, in the trans-Golgi network, or in cytoplasmic vesicles and that this event is dependent on the expression of PKA in these cells.NEW & NOTEWORTHY Phosphorylation of aquaporin-2 by PKA at serine 256 (S256) occurs in various subcellular locations during its recycling itinerary, suggesting that the protein complex necessary for AQP2 S256 phosphorylation is present in these different recycling stations. Furthermore, we showed, using PKA-null cells, that PKA activity is required for vasopressin-induced AQP2 phosphorylation. Our data reveal a complex spatial pattern of intracellular AQP2 phosphorylation at S256, shedding new light on the role of phosphorylation in AQP2 membrane accumulation.

Guided antipsychotic reduction to reach minimum effective dose (GARMED) in patients with remitted psychosis: a 2-year randomized controlled trial with a naturalistic cohort.

BACKGROUND: Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse. METHODS: A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life. RESULTS: A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life. CONCLUSIONS: GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

Follow-up of subjects labelled with putative pre-psychotic states: Viewed from a transdiagnostic clinical high-at-risk mental state (CHARMS) paradigm.

BACKGROUND: Follow-up of subjects with putative pre-psychotic states is essential to clarify the transition process to psychosis, while "non-converters" also deserve clinical attention as many may evolve into other psychiatric disorders with diverse outcomes. This study aimed to examine help-seeking individuals who have been labelled at clinical high-risk state but not converting to full-blown psychosis during first two years of follow-up. METHODS: A retrospective observational cohort study of help-seeking subjects was conducted by reviewing medical records of participants in a previous early psychosis study at the study hospital between 2006 and 2020. We portrayed those who developed first episode psychosis after first 2-year follow-up in detail, and provided sketches of clinical macrophenotypes other than psychosis emerging from subjects among different risk groups. RESULTS: Among 132 eligible subjects, data of 98 (74.2%) were available for detailed evaluation. Of these, 15 transitioned to first-episode psychosis (11.4%) with time to psychosis from 2 to 11 years, 11 had anxiety spectrum (8.3%), 11 had depressive spectrum (8.3%), 10 had obsessive compulsive (7.6%), 5 had bipolar spectrum disorders (3.8%), 13 had predominantly schizotypal (9.8%) and 4 had other personality traits (3%), and 13 had problems attributable to adjustment or developmental issues (9.8%). CONCLUSION: Various diagnoses, either full- or sub-threshold, appropriately describe the diverse clinical phenomenology of a cohort presenting with non-specific and/or subthreshold psychotic symptoms. The clinical high-at-risk mental state (CHARMS) paradigm provides a reasonable transdiagnostic approach for orienting clinicians' attention toward young subjects seeking mental health help at an early stage of illness to potentially pluripotent trajectories.

Augmenting the effect of virtual labs with "teacher demonstration" and "student critique" instructional designs to scaffold the development of scientific literacy.

Virtual labs provide space for students to iteratively test, observe, and revise their understanding so as to improve their scientific literacy. However, one of the challenges that students face is that they need to think and act like scientists so as to be sensitively alert to methodological flaws and various sources of error. This study thus compared the effect of two instructional approaches using a virtual lab to enhance students' scientific literacy. Before students were given the opportunity to conduct science inquiries with the virtual lab, they were required to critique problematic inquiry cases (the critique group) or watch teachers' demonstrations (the teacher demonstration group) before taking part in the inquiry. By analyzing data from 50 middle school students, this study found that the effect of applying virtual labs can be augmented by an instructional design that engages students in critiquing experiments prior to their inquiry with the virtual lab. This study also found a limitation of the use of virtual labs in helping students transfer what they have learned from the teacher's demonstration to new inquiry contexts. A close relation among scientific literacy post-test scores, critiquing performance, and inquiry performance in the inquiry activity was detected, suggesting that student critiquing prior to inquiry is in alignment with the goal of developing students' inquiry skills and scientific literacy with virtual labs.

Actin-related protein 2/3 complex plays a critical role in the aquaporin-2 exocytotic pathway.

The trafficking of proteins such as aquaporin-2 (AQP2) in the exocytotic pathway requires an active actin cytoskeleton network, but the mechanism is incompletely understood. Here, we show that the actin-related protein (Arp)2/3 complex, a key factor in actin filament branching and polymerization, is involved in the shuttling of AQP2 between the trans-Golgi network (TGN) and the plasma membrane. Arp2/3 inhibition (using CK-666) or siRNA knockdown blocks vasopressin-induced AQP2 membrane accumulation and induces the formation of distinct AQP2 perinuclear patches positive for markers of TGN-derived clathrin-coated vesicles. After a 20°C cold block, AQP2 formed perinuclear patches due to continuous endocytosis coupled with inhibition of exit from TGN-associated vesicles. Upon rewarming, AQP2 normally leaves the TGN and redistributes into the cytoplasm, entering the exocytotic pathway. Inhibition of Arp2/3 blocked this process and trapped AQP2 in clathrin-positive vesicles. Taken together, these results suggest that Arp2/3 is essential for AQP2 trafficking, specifically for its delivery into the post-TGN exocytotic pathway to the plasma membrane.NEW & NOTEWORTHY Aquaporin-2 (AQP2) undergoes constitutive recycling between the cytoplasm and plasma membrane, with an intricate balance between endocytosis and exocytosis. By inhibiting the actin-related protein (Arp)2/3 complex, we prevented AQP2 from entering the exocytotic pathway at the post-trans-Golgi network level and blocked AQP2 membrane accumulation. Arp2/3 inhibition, therefore, enables us to separate and target the exocytotic process, while not affecting endocytosis, thus allowing us to envisage strategies to modulate AQP2 trafficking and treat water balance disorders.

Development of the CAT-FER: A Computerized Adaptive Test of Facial Emotion Recognition for Adults With Schizophrenia.

IMPORTANCE: The most frequently used measures of facial emotion recognition (FER) are insufficiently comprehensive, reliable, valid, and efficient; moreover, the impact of gender on scoring has not been controlled. OBJECTIVE: To develop a computerized adaptive test of FER for adults with schizophrenia. DESIGN: First, we selected photographs from a published database. Second, items that fitted well to a Rasch model were used to form the item bank. Third and last, we determined the best administration mode for prospective users to achieve both high reliability and efficiency. SETTING: Psychiatric hospitals and the community. PARTICIPANTS: Adults living with schizophrenia (n = 351) and adults without diagnosed mental illness (n = 101). RESULTS: After removal of misfit items (infit or outfit ≥1.4), the remaining 165 items were selected to form an item bank. Among them, 39 showed severe gender bias, so the item difficulties were adjusted accordingly. On the basis of the item bank, two administration modes were recommended for prospective users. The reliable mode required approximately 128 items (nearly 20 min) to achieve reliability (.72-.81), similar to that of the entire item bank. The efficient mode required approximately 73 items (approximate 11 min) to provide acceptable reliability (.69-.73) for the seven domain scores. CONCLUSIONS AND RELEVANCE: Our newly developed measure provides comprehensive, valid, and unbiased (to examinees' gender) assessments of FER in adults living with schizophrenia. In addition, the administration modes can be flexibly changed to optimize the reliability or efficiency for prospective users. WHAT THIS ARTICLE ADDS: This newly developed FER measure can help occupational therapists identify deficits in recognizing specific basic emotions and plan corresponding interventions to manage the impact on their clients' social functions.

Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?

BACKGROUND: Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients. METHODS: Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound. RESULTS: Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms. CONCLUSIONS: An abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia. TRIAL REGISTRATION: NCT00545467 ; Date of registration: 17/10/2007.

Social cognition in schizophrenia: A network-based approach to a Taiwanese version of the Reading the Mind in the Eyes test.

BACKGROUND: This study aimed to examine social-cognitive impairments in patients with schizophrenia using the Eyes test. In contrast to previous methods using the correct answers, we developed the Taiwanese version of the Eyes test and constructed the response network to explore impairments in the emotional aspects of theory of mind in patients with schizophrenia. METHODS: Eighteen patients with schizophrenia and 18 healthy controls were recruited to examine their performance of the Eyes test. To explore the internal structures of mental states, we used network analysis to construct the networks of choice patterns (i.e. participants' answers) by using two network indicators, including density (an index of structure diversity of a network) and centrality (an index of the choice patterns within a network). Moreover, we divided all the choices into negative, positive, and neutral item groups based on emotion polarity. RESULTS: The patient group was slower and less accurate than the control group. Moreover, there was a negative correlation between accuracy and blunted affect, and there were positive correlations between reaction time and emotional withdrawal and apathetic social withdrawal. As compared to healthy controls, patients with schizophrenia showed larger density in the network structure and higher centrality than controls. Also, patients showed poorer performance on negative words than healthy controls. CONCLUSION: Our results demonstrated more diversity to recognize negative emotions from patients' choice patterns as compared to those in the control group. These findings suggest that deficits on recognizing negative emotions might be associated with the dysfunctions of mental states in schizophrenia.

Genetic associations and expression of extra-short isoforms of disrupted-in-schizophrenia 1 in a neurocognitive subgroup of schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.

Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia.

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post-hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.

Time trends in first admission rates for schizophrenia and other psychotic disorders in Taiwan, 1998-2007: a 10-year population-based cohort study.

PURPOSE: To examine the trend in annual first admission rates for psychotic disorders as a whole as well as individual psychotic disorders in Taiwan from 1998 to 2007, and influences of age, sex, and geographic region on the trend. METHOD: Using the inpatient claims records in the National Health Insurance Research Database, we estimated the yearly first admission rates for schizophrenia and other psychotic disorders, including voluntary (1998-2007) and involuntary (2004-2007) admissions. Both narrow and broad definitions of psychotic disorders were examined. RESULTS: While involuntary first admission rates were stable, a crescendo-decrescendo change in voluntary first admission rates for psychotic disorders was observed, peaking in 2001. The increase from 1998 to 2001 was closely associated with health insurance expansion. Before 2001, the voluntary first admission rates in males aged 15-24 were underestimated as military personnel records were not included in the database. From 2001 to 2007, voluntary first admissions for psychotic disorders decreased 38%; the decrease could not be accounted for by the mild diagnostic shifts away from schizophrenia to affective psychosis or substance-induced psychosis. During the entire observation period, first admission rates for schizophrenia decreased 48%, while affective psychosis increased 84%. Gender disparities in the first admission rates gradually diminished, but geographic disparities persisted. CONCLUSIONS: First admission rates for psychosis significantly reduced in Taiwan between 1998 and 2007, mainly driven by the reduced hospitalization risk for schizophrenia. Special attention should be paid to the increased hospitalization for other types of psychotic disorders (especially affective psychosis) and the unresolved geographic disparities.

Altered integrity of the right arcuate fasciculus as a trait marker of schizophrenia: a sibling study using tractography-based analysis of the whole brain.

Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association.

Automatic whole brain tract-based analysis using predefined tracts in a diffusion spectrum imaging template and an accurate registration strategy.

Automated tract-based analysis of diffusion MRI is an important tool for investigating tract integrity of the cerebral white matter. Current template-based automatic analyses still lack a comprehensive list of tract atlas and an accurate registration method. In this study, tract-based automatic analysis (TBAA) was developed to meet the demands. Seventy-six major white matter tracts were reconstructed on a high-quality diffusion spectrum imaging (DSI) template, and an advanced two-step registration strategy was proposed by incorporating anatomical information of the gray matter from T1-weighted images in addition to microstructural information of the white matter from diffusion-weighted images. The automatic analysis was achieved by establishing a transformation between the DSI template and DSI dataset of the subject derived from the registration strategy. The tract coordinates in the template were transformed to native space in the individual's DSI dataset, and the microstructural properties of major tract bundles were sampled stepwise along the tract coordinates of the subject's DSI dataset. In a validation study of eight well-known tracts, our results showed that TBAA had high geometric agreement with manual tracts in both deep and superficial parts but significantly smaller measurement variability than manual method in functional difference. Additionally, the feasibility of the method was demonstrated by showing tracts with altered microstructural properties in patients with schizophrenia. Fifteen major tract bundles were found to have significant differences after controlling the family-wise error rate. In conclusion, the proposed TBAA method is potentially useful in brain-wise investigations of white matter tracts, particularly for a large cohort study.

Initiating long-acting injectable antipsychotics during acute admission for patients with schizophrenia--A 3-year follow-up.

BACKGROUND/PURPOSE: The debate on whether long-acting injectable antipsychotic (LAIA) medication is superior to oral medication, in preventing rehospitalization of patients with schizophrenia, remains inconclusive. We compared rehospitalization rates over 3 years following discharge from an acute admission, in which patients either began using LAIAs regularly for the first time, or continued to use oral antipsychotics. METHODS: A retrospective observational study of 92 inpatients with schizophrenia from a university-based medical center during 2004-2008. The primary outcome measure is the rehospitalization rates between groups, as estimated by Kaplan-Meier survival analysis. RESULTS: Eighteen of 47 (38.3%) LAIA patients, and 16 of 45 (35.6%) oral medication patients were rehospitalized (average time to rehospitalization, 378 ± 262 vs. 378 ± 340 days; p = 0.997). The estimated cumulative rates of rehospitalization were similar between groups. The overall odds comparing the LAIA to the oral medication group were 1.085 ± 0.373 (95% confidence interval: 0.553-2.13, p = 0.813). Compared to the oral medication group, the LAIA group had fewer coded with sufficient previous treatment response (32% vs. 69%, p < 0.001), more poorly compliant (91% vs. 56%, p < 0.001), and a slightly longer length of stay at index admission (32.7 ± 11.3vs. 27.6 ± 12.1, p = 0.04). CONCLUSION: Initiating LAIAs during admission for an acute psychotic episode, to a group of patients with an inadequate previous treatment response and poorer compliance, might keep their rehospitalization rates to the level of their oral antipsychotic medication treated counterparts.

Frequency-specific alternations in the amplitude of low-frequency fluctuations in schizophrenia.

Schizophrenia has been associated with abnormal task-related brain activation in sensory and motor regions as well as social cognition network. Recently, two studies investigated temporal correlation between resting-state functional magnetic resonance imaging (R-fMRI) low-frequency oscillations (LFOs) in schizophrenia but reported mixed results. This may be due to the different frequency bands used in these studies. Here we utilized R-fMRI to measure the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) in three different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.08 Hz; and typical band: 0.01-0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. We showed that there were significant differences in ALFF/fALFF between the two bands (slow-5 and slow-4) in regions including basal ganglia, midbrain, and ventromedial prefrontal cortex. Importantly, we also identified significant interaction between frequency bands and groups in inferior occipital gyrus, precuneus, and thalamus. The results suggest that the abnormalities of LFOs in schizophrenia is dependent on the frequency band and suggest that future studies should take the different frequency bands into account when measure intrinsic brain activity.

Work performance and its clinical correlates in patients with chronic mental illness: The Chinese version of Vocational Cognitive Rating Scale and the work behavior inventory.

OBJECTIVE: Occupational function assessment is essential for rehabilitation of severe mental illness but lacks comprehensive tools. METHOD: This study examines the psychometric properties of the Chinese versions of the Vocational Cognitive Rating Scale (VCRS) and the Work Behavior Inventory (WBI) in 60 chronic patients from a psychiatric daycare center and identifies clinical correlates of occupational function measured on the Positive and Negative Syndrome Scale (PANSS). RESULTS: The Chinese VCRS and WBI showed adequate internal consistency, interrater and test-retest reliability, and good convergent validity with the Comprehensive Occupational Therapy Evaluation Scale. Factor analysis favored a one-factor solution of the VCRS; and a four-factor structure in the WBI including Efficiency, Social Interaction, Appropriateness, and Regularity. The VCRS and Efficiency were predicted by fewer disorganization but greater affective symptoms. Social Interaction was negatively predicted by resistance symptoms. Appropriateness was associated with all but negative symptoms. Regularity was predicted by fewer negative symptoms. Considering work behavior altogether, WBI total scores were predicted by fewer negative, fewer disorganization, and greater affective symptoms. CONCLUSIONS AND IMPLICATION FOR PRACTICE: Findings suggest that the Chinese VCRS and WBI have sound psychometric properties and are suitable for both clinical trials and for planning personalized rehabilitation programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

In-Hospital Use of Long-Acting Injectable Antipsychotics and Readmission Risk in Patients With First-Admission Schizophrenia in Taiwan.

Importance: Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge. Objective: To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs. Design, Setting, and Participants: This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022. Exposure: In-hospital use of LAIs with or without early discontinuation. Main Outcome and Measures: Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model. Results: Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model. Conclusions and Relevance: The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.

Aripiprazole for drug-naive or antipsychotic-short-exposure subjects with ultra-high risk state and first-episode psychosis: an open-label study.

INTRODUCTION: This study aimed to observe treatment response using aripiprazole for subjects with ultra-high risk (UHR) state of psychosis or at their first-episode psychosis (FEP) who were drug-naive or only have received antipsychotic therapy temporarily. METHODS: All patients received aripiprazole 3.75 mg/d initially to test tolerability and increased to 7.5 mg during the first 2 weeks. A flexible dosing strategy based on clinical improvement and tolerability with a target dose 15 mg/d by the end of the fourth week. Clinical severity was assessed by a Mandarin version of the positive and negative syndrome scale for schizophrenia at baseline, the end of the second and the fourth week. Adverse reactions were recorded by a log, and concomitant medications were allowed. RESULTS: A total of 20 FEP and 11 UHR patients, including 18 drug-naive (11 FEP and 7 UHR) and 13 antipsychotic-short-exposure patients (9 FEP and 4 UHR), participated in and 29 completed the study. Most of them received aripiprazole no more than 7.5 mg/d at end point with favorable response, although many of them reported adverse events. Both UHR and FEP patients got significant decrease of positive symptom scores in a similar pattern. Both groups did not show significant changes in negative symptom scores. CONCLUSION: The treatment response of UHR patients is likely a continuum from that of the FEP patients. Low-dose aripiprazole revealed potential efficacy for patients with less severe psychopathology, at putative prodromal or early state of psychosis, yet still was accompanied by adverse events while treating this mostly drug-naive population.