Dose-tapering trajectories in patients with remitted psychosis undergoing guided antipsychotic reduction to reach minimum effective dose.

Background: Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.

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.

Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in Heterozygous Mutant Mice, a Putative Prodromal Schizophrenia Animal Model.

Symptoms of schizophrenia (SZ) typically emerge during adolescence to young adulthood, which gives a window before full-blown psychosis for early intervention. Strategies for preventing the conversion from the prodromal phase to the psychotic phase are warranted. Heterozygous (Het) mutant mice are considered a prodromal model of SZ, suitable for studying psychotic conversion.

The plasma level of complement component 4A decreases with aripiprazole treatment in patients with early psychosis.

The complement component 4 (C4) gene has been reported to be significantly associated with schizophrenia, and C4A RNA expression was found to increase in postmortem brains of schizophrenia patients. This study aimed to examine the plasma levels of C4A and C4B proteins in patients with early psychosis and their changes following aripiprazole treatment. We recruited 45 patients, including 17 patients with ultra-high-risk and 28 patients with first-episode psychosis, and 45 age-matched and sex-matched controls.

Niacin skin flush and membrane polyunsaturated fatty acids in schizophrenia from the acute state to partial remission: a dynamic relationship.

Despite the consistent finding of an attenuated niacin-induced flush response in schizophrenia, its long-term stability and relationship to the membrane polyunsaturated fatty acid (PUFA) levels remain unknown. We conducted niacin skin tests and measured the membrane PUFAs using gas chromatography among 46 schizophrenia inpatients and 37 healthy controls at the baseline and the 2-month follow-up. Attenuated flush responses were persistently observed in schizophrenia patients in both acute and partial remission states, whereas an increased flush response was found in the controls.

Neurodevelopmental model of schizophrenia revisited: similarity in individual deviation and idiosyncrasy from the normative model of whole-brain white matter tracts and shared brain-cognition covariation with ADHD and ASD.

The neurodevelopmental model of schizophrenia is supported by multi-level impairments shared among schizophrenia and neurodevelopmental disorders. Despite schizophrenia and typical neurodevelopmental disorders, i.e.

Detection of advanced brain aging in schizophrenia and its structural underpinning by using normative brain age metrics.

Conceptualizing mental disorders as deviations from normative functioning provides a statistical perspective for understanding the individual heterogeneity underlying psychiatric disorders. To broaden the understanding of the idiosyncrasy of brain aging in schizophrenia, we introduced an imaging-derived brain age paradigm combined with normative modeling as novel brain age metrics. We constructed brain age models based on GM, WM, and their combination (multimodality) features of 482 normal participants.

Discontinuing Antipsychotic Medication After Remission from First-Episode Psychosis: A Survey of Psychiatrists' Attitudes in Taiwan.

Background: Patients in remission after first-episode psychosis are inclined to discontinue antipsychotic treatment, which may lead to higher risk of relapse and unfavorable outcomes. Paradoxically, also there are evidences suggesting that certain patients may stay well in drug-free condition. Psychiatrists' views towards this dilemma might affect their approaches to these patients, and discrepant attitudes are noted between Western and Asian clinicians.

Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia.

Background: Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.

Objective: This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.

Methods: We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies.

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.

Challenging the Minimum Effective Antipsychotic Dose During Maintenance: Implications From 10-Year Follow-Up of First Episode Psychosis.

Contradictory messages regarding the necessity of long-term antipsychotic treatment after first episode psychosis arouse deliberations in clinical practice. We explored if there is an alternative beyond the dichotomy of maintenance treatment and discontinuation of medications. We conducted a retrospective observational study by reviewing medical records at the study hospital of a cohort of patients since their participation in an early psychosis study starting from 2006, with special interests in patients able to maintain good functioning under treatment with a low antipsychotic dose.

Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations.

People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.

Impaired response to sleep deprivation in heterozygous mutant mice.

Objectives: Sleep/circadian rhythm disturbances are environmental stress factors that might interact with genetic risk factors and contribute to the pathogenesis of psychiatric disorders.

Methods: In this study, the multiple-platform method was used to induce sleep deprivation (SD). We evaluated the impact of 72-hour SD in behavioural, anatomical, and biochemical aspects in heterozygous mutant ( Het) mice, an animal model of schizophrenia.

Protocol of guided antipsychotic reduction to reach minimum effective dose (GARMED) in patients with remitted psychosis based on pragmatic design.

Aims: Patients with psychosis intend to discontinue antipsychotic treatment for various reasons. As antipsychotic discontinuation involves a high risk of relapse, maintenance treatment is recommended by mainstream opinion even when remission is attained. To optimize the risk-to-benefit ratio of long-term antipsychotic treatment, we proposed an operationalized guided dose-reduction algorithm to serve as an intermediate approach as to achieve the lowest effective antipsychotic dose and better functioning for patients with remitted psychosis.

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.

P50, N100, and P200 Auditory Sensory Gating Deficits in Schizophrenia Patients.

Background: Sensory gating describes neurological processes of filtering out redundant or unnecessary stimuli during information processing, and sensory gating deficits may contribute to the symptoms of schizophrenia. Among the three components of auditory event-related potentials reflecting sensory gating, P50 implies pre-attentional filtering of sensory information and N100/P200 reflects attention triggering and allocation processes. Although diminished P50 gating has been extensively documented in patients with schizophrenia, previous studies on N100 were inconclusive, and P200 has been rarely examined.

Generalization of diffusion magnetic resonance imaging-based brain age prediction model through transfer learning.

Brain age prediction models using diffusion magnetic resonance imaging (dMRI) and machine learning techniques enable individual assessment of brain aging status in healthy people and patients with brain disorders. However, dMRI data are notorious for high intersite variability, prohibiting direct application of a model to the datasets obtained from other sites. In this study, we generalized the dMRI-based brain age model to different dMRI datasets acquired under different imaging conditions.

Clinical implications of oxidative stress in schizophrenia: Acute relapse and chronic stable phase.

Several studies have suggested a higher oxidative stress in schizophrenia. However, the implications of oxidative stress on clinical symptoms remain unclear. This study aimed to investigate the platelet oxidative stress in different stages of schizophrenia (i.

Comparative genetic architectures of schizophrenia in East Asian and European populations.

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci.