Exploring the latent cognitive structure in schizophrenia: implications for antipsychotic treatment responses.

BACKGROUND: Individuals diagnosed with schizophrenia present diverse degrees and types of cognitive impairment, leading to variations in responses to antipsychotic treatments. Understanding the underlying cognitive structures is crucial for assessing this heterogeneity. Utilizing latent profile analysis (LPA) enables the delineation of latent categories of cognitive function. Integrating this approach with a dimensional perspective allows for the exploration of the relationship between cognitive function and treatment response. METHODS: This study examined 647 patients from two distinct cohorts. Utilizing LPA within the discovery cohort (n = 333) and the replication cohort (n = 314), latent subtypes were identified categorically. The stability of cognitive structures was evaluated employing Latent Transition Analysis (LTA). The relationship between cognitive function and treatment response were investigated by comparing Positive and Negative Syndrome Scale (PANSS) reduction rates across diverse cognitive subtypes. Furthermore, dimensional insights were gained through correlation analyses between cognitive tests and PANSS reduction rates. RESULTS: In terms of categorical, individuals diagnosed with schizophrenia can be categorized into three distinct subtypes: those 'without cognitive deficit', those 'with mild-moderate cognitive 'eficit', and those 'with moderate-severe cognitive deficit'. There are significant differences in PANSS reduction rates among patients belonging to these subtypes following antipsychotic treatment (p < 0.05). Furthermore, from a dimensional perspective, processing speed at baseline is positively correlated with PANSS score reduction rates at week 8/week 10 (p < 0.01). CONCLUSIONS: Our findings have unveiled the latent subtypes of cognitive function in schizophrenia, illuminating the association between cognitive function and responses to antipsychotic treatment from both categorical and dimensional perspectives.

Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia.

The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.

The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial.

Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).

Multishape Programming of Shape Memory Polymer Assemblies Fabricated by Vat Photopolymerization-Based 3D Printing and Interfacial Welding.

The combination of three-dimensional (3D) printing and shape memory polymers (SMP) enables programmable shape morphing of complex 3D structures, which is commonly termed four-dimensional (4D) printing. The process requirements of vat photopolymerization-based 3D printing impose limitations on the molecular structure design of SMPs, making it challenging to achieve triple- or multiple-shaped memory effects. Herein, we printed SMPs with different Tg values and obtained an SMP assembly through interfacial welding. The welding process is facilitated by the dynamic exchange of hindered urethane bonds at the interface. The resulting SMP assembly exhibits a quadruple shape memory effect, enabling programmable sequential deformation. The advantage of this approach is that the molecular design and the corresponding thermodynamic properties of different welding SMP components can be independently adjusted, enabling a greater range of shape and functional variations in the final 3D SMP assembly.

The Effect of Accelerated Continuous Theta Burst Stimulation on Weight Loss in Overweight Individuals With Schizophrenia: A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

BACKGROUND AND HYPOTHESIS: Obesity is a common comorbidity in individuals with schizophrenia and is associated with poor clinical outcomes. At present, there are limited effective approaches for addressing this issue. We conducted a double-blind, randomized, sham-controlled clinical trial to investigate the efficacy of noninvasive magnetic stimulation techniques in reducing obesity in individuals with schizophrenia. STUDY DESIGN: Forty overweight individuals with schizophrenia were recruited and randomly assigned to receive either the active or sham intervention. The active group received 50 accelerated continuous theta burst stimulation (cTBS) sessions over the left primary motor area (M1), while the sham group received sham stimulation. The primary outcomes were the change in body weight and body mass index (BMI), and the secondary outcomes were the psychiatric symptoms, eating behavior scales, metabolic measures, and electrophysiological to food picture stimuli. STUDY RESULTS: The study demonstrated a significant decrease in body weight and BMI after the intervention selectively in the active group (mean = -1.33 kg, P = .002), and this improvement remained at the 1-month follow-up (mean = -2.02 kg, P = .008). The score on the Barratt Impulsivity Scale (mean = -1.78, P = 0.036) decreased in the active group and mediated the effect of accelerated cTBS on body weight. In the food picture cue electroencephalograph task, the late positive potential component, which is related to motivated attention and emotional processing, decreased in frontal brain regions and increased in posterior regions after the active intervention. CONCLUSIONS: The accelerated cTBS may offer a promising approach for treating obesity in individuals with schizophrenia. Further research with a larger sample size or individualized stimulation protocol should be promising. TRIAL REGISTRATION: Clinical trial registered with clinicaltrials.gov (NCT05086133).

Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics.

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.

Efficient removal of cationic dyes via activated carbon with ultrahigh specific surface derived from vinasse wastes.

In this work, a simple and feasible approach for converting waste vinasse generated from the alcohol industries into high value-added activated carbon (AC) was proposed. The obtained AC possessed abundant micropores with micropore volume of 0.9613 cm3/g and ultrahigh specific surface areas (2015 m2/g), indicating prominent adsorption capacity. The adsorption ability of AC to cationic methylene blue (MB) was investigated systematically. The resultant AC exhibited superior adsorption ability to MB with a maximum amount of 2251 mg/g, derived from its excellent pore textural features and abundant surface O-containing functional groups. Moreover, AC showed excellent removal efficiency for treating industrial polyacrylonitrile wastewater with 99% removal within 60 min. Our results provide great inspirations in solid waste treatment and their high value-added transformation, meanwhile exploit a promising application of AC for practical wastewater purification.