Chemotherapy-induced cognitive impairment, commonly referred to as "chemobrain", represents a frequent and distressing complication of cancer therapy. Doxorubicin (DOX), a widely used chemotherapeutic agent, contributes to these deficits partly through mechanisms involving oxidative stress, inflammatory cascades, and disruption of glutamate homeostasis, but unfortunately, the precise role of altered glutamate transport and neurotrophic signaling remains poorly addressed. Lurasidone (LURA), an atypical antipsychotic, exhibits potent 5-HT7 receptor antagonism and pro-cognitive properties, making it a strong candidate to counteract these deficits. However, its potential to rescue glutamate homeostasis and neuroplasticity pathways in chemobrain has not been explored. This study investigated whether LURA could counteract DOX-induced chemobrain by restoring CREB/BDNF/Glt-1 signaling and re-establishing glutamate homeostasis in the hippocampus and prefrontal cortex.

Agitation is a common and clinically significant neuropsychiatric condition in Alzheimer's dementia. Clinicians across the spectrum of care settings frequently encounter agitation but often lack practical clinical guidance. In April 2026, a consensus panel of clinical experts reviewed the literature and developed guidance for managing agitation in Alzheimer's dementia. The panel emphasized the critical role of primary care in agitation management and discussed different treatment approaches for optimizing patient and caregiver outcomes. Treatment should prioritize reduction of patient and caregiver distress and preservation of function rather than mere sedation. Discussion of neurobiology focused on the evolving models of frontal-limbic imbalance as the key driver of agitation in progressing Alzheimer's disease and implications for pharmacologic selection. The panel reviewed evidence on safety and efficacy of pharmacologic agents commonly used in agitation management and concluded that efficacy and safety profiles should guide clinical decision-making. The panel recommended conducting a behavioral assessment using validated tools, ruling out reversible causes, and using nonpharmacologic interventions as the first-line approach prior to starting pharmacologic treatment. Finally, setting-specific considerations were discussed. These recommendations complement prior guidance with a primary-care clinical decision pathway that matches treatment to the neurobiology of agitation and to comparative safety profiles, and that extends to the assessment, documentation, and coding clinicians need at the point of care. The goal is to help clinicians select evidence-based interventions for agitation in Alzheimer's dementia that prioritize safety, alertness, functional engagement, and caregiver well-being while minimizing the serious harms that have historically accompanied off-label management in this population, including excess mortality, cerebrovascular events, cognitive impairment, falls, and sedation.

MRI studies have revealed structural brain abnormalities in obsessive-compulsive disorder (OCD). Less is known about how age and medication influence them. We analyzed cortical thickness (CT) data from the ENIGMA-OCD Consortium, the world's largest OCD MRI database (46 datasets from 35 centers). Subjects comprised 2057 healthy controls, 1167 unmedicated individuals with OCD, and 1073 individuals with OCD taking one or more psychiatric medications at time of scan. Using a harmonized FreeSurfer protocol, each MRI was parcellated into 68 cortical regions. Linear mixed models controlling for site and symptom severity mapped associations of OCD diagnosis and medication-any psychiatric medication and the medication classes serotonin-reuptake inhibitors (SRIs), tricyclics, antipsychotics, and benzodiazepines-on CT and their interaction with age in each region. Findings surviving FDR-correction included: 1) Unmedicated OCD participants showed thicker cortex and/or lesser CT decrease with age than controls in precentral, inferior parietal, superior parietal, and superior temporal regions (p < .001-.002); 2) In several regions, OCD participants taking any medication had thinner cortex than unmedicated; negative associations of age with CT were similar to controls (p < .001-.005). 3) Findings for SRIs resembled those in for any psychiatric medication. 4) CT was lower in participants taking benzodiazepines than in unmedicated participants in 30 regions (p < .001-.014). No associations of CT involving tricyclics or antipsychotics survived FDR-correction. Commonly prescribed OCD drugs may influence CT in ways that vary with cortical region and medication class. Potential mechanisms are discussed.

Akathisia, a prevalent drug-induced movement disorder, is characterized by inner restlessness and an irresistible urge to move. It can occur after starting a new medication, increasing the dose, or switching to another medication. It is commonly associated with, but not limited to antipsychotic use. Tacrolimus (TAC), an immunosuppressant vital for preventing acute rejection post-solid organ transplantation, has been linked to various neurological side effects. Neurotoxic side effects of TAC may include headache, seizures, tremor, encephalopathy, and peripheral pain. This report details a case of TAC-induced akathisia in a post-cardiac transplant patient, emphasizing the need for heightened clinical suspicion and awareness of this underreported phenomenon. The patient's symptoms, including restlessness and an inability to sit still, were exacerbated by TAC, prompting a diagnosis and subsequent treatment for akathisia.

Second-generation antipsychotics are effective for a range of pediatric psychiatric and behavioral conditions but are commonly associated with weight gain and metabolic dysfunction. Metformin is the most extensively studied pharmacological strategy for preventing or treating this adverse effect; however, the randomized evidence base has evolved substantially with the publication of recent large trials. This study aimed to systematically review and meta-analyze randomized controlled trials of metformin and other metabolic-protective strategies, including topiramate, melatonin, and antipsychotic switching, for preventing or treating antipsychotic-associated weight gain in children and adolescents. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for records published between January 2000 and June 2026. Randomized controlled trials enrolling participants aged 19 years or younger who were receiving a second-generation antipsychotic were eligible. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses using restricted maximum likelihood estimation with the Hartung-Knapp adjustment pooled mean differences and risk ratios when at least two trials contributed comparable data; prevention and treatment indications were analyzed separately. Seven unique randomized controlled trials reported across eight publications met eligibility criteria, including 1,871 participants: five trials evaluated metformin, one evaluated topiramate, and one evaluated melatonin. The pooled effect of metformin on body mass index (BMI) z-score, the primary outcome, favored treatment at all time windows but was not statistically significant (short-term, three trials: mean difference [MD] = -0.093, 95% confidence interval [CI] -0.250 to 0.063; medium-term, two trials: MD = -0.090, 95% CI -0.346 to 0.166; long-term, one trial: MD = -0.07, 95% CI -0.145 to 0.005). Short-term body weight was significantly reduced with metformin (three trials: MD = -2.30 kg, 95% CI -4.28 to -0.32). Metabolic laboratory outcomes were imprecise and inconsistent in direction, and diarrhea was numerically more frequent with metformin. Evidence for topiramate, melatonin, and antipsychotic switching was limited to single trials or trial arms. No included trial was rated as having an overall low risk of bias. Metformin has the largest randomized pediatric evidence base among metabolic-protective strategies and consistently attenuated weight gain compared with control; however, its pooled effect on the primary outcome did not reach statistical significance at any time window, and metabolic benefits could not be confirmed. Decisions regarding metabolic-protective strategies should be individualized rather than universally applied, and larger, longer, standardized pediatric trials are needed.

Persistent negative symptoms and cognitive deficits remain major obstacles to functional recovery in schizophrenia. These impairments are often only partially responsive to antipsychotic treatment and may persist even when other symptoms are clinically stable. Psychosocial interventions show inconsistent efficacy, and commonly used non-invasive brain stimulation techniques have limited ability to target deeper cortical regions. Transcranial temporal interference stimulation (tTIS) has recently emerged as a promising approach for modulating neural activity in such regions. This trial aims to evaluate the clinical efficacy of tTIS targeting the dorsal anterior cingulate cortex (dACC) in individuals with schizophrenia.

BackgroundIndividuals with schizophrenia and concurrent substance use disorders (SUDs) face a high risk of rapid weight gain during residential treatment, driven by inpatient environmental factors, baseline metabolic vulnerability, and metabolically active psychotropic medications. Clozapine, commonly indicated for treatment-resistant psychosis, is frequently associated with early and substantial weight gain. This study examined whether adjunctive metformin or aripiprazole attenuated weight gain in individuals taking clozapine in a naturalistic residential setting.MethodsThis retrospective cohort study included adults prescribed clozapine during admission to a 105-bed provincial concurrent disorders facility in British Columbia, Canada (2021-2024). Adults with ≥90-day admissions and available therapeutic drug monitoring were included. Monthly weights were extracted from electronic records and linked to serum concentrations and medication exposure. Linear mixed-effects models with random intercepts and slopes assessed predictors of weight trajectories, with fixed effects including age, sex, baseline weight, norclozapine concentration, opioid agonist therapy (OAT), augmenting antipsychotic defined daily dose, and adjunctive metformin and aripiprazole. Interaction terms between time and adjunctive agents evaluated effects on weight trajectories.ResultsEighty individuals contributed 306 matched serum concentration-weight observations. The cohort was predominantly male with schizophrenia and comorbid SUDs. Higher baseline weight and greater time between admission and blood draw were associated with increased weight. In adjusted models, norclozapine concentration and OAT were associated with higher weight. Metformin was associated with attenuation of weight gain over time (time × metformin: B = -2.63, 95% CI -4.49 to -0.76), whereas aripiprazole was not (B = -0.38, 95% CI -2.58 to 1.82).ConclusionMetformin was associated with attenuation of weight gain trajectory in this population, whereas aripiprazole showed no clear effect. These findings highlight substantial metabolic vulnerability in inpatient concurrent disorders settings and support early preventive metabolic interventions during clozapine treatment.

Antipsychotics represent mainstay treatment of schizophrenia and are also prescribed on- and off-label in other severe mental illnesses. Newer antipsychotic use is associated with severe metabolic side effects such as obesity and type 2 diabetes. Leptin is a hormone secreted by adipose tissue, and it acts on the brain to decrease body weight by reducing food intake and stimulating energy expenditure. Leptin also improves glucose and lipid metabolism. In this study, we examined the short-term impact of olanzapine, a commonly used second-generation antipsychotic, on the central leptin-mediated regulation of energy balance, glucose and lipid metabolism, and hypothalamic kinase activity. Male SD rats were given an acute intracerebroventricular (ICV) injection of either leptin or vehicle, combined with subcutaneous olanzapine or vehicle. As expected, ICV leptin decreased food intake and, importantly, olanzapine did not block this effect. Administration of leptin, olanzapine, or their combination reduced the average respiratory exchange ratio (RER) during the light-cycle, indicating increased fat oxidation. In the dark-cycle, leptin decreased the average RER regardless of olanzapine administration, and in the presence of leptin, olanzapine did not affect the average RER. Olanzapine treatment produced transient glucose intolerance during the IPGTT, an effect no longer observed with leptin co-treatment, though no significant differences in AUC, fasting serum glucose, insulin, or HOMA-IR were observed between any groups. Olanzapine and leptin treatment differentially activated hypothalamic kinases. In conclusion, the regulation of food intake and fuel preference by central leptin remains intact despite acute olanzapine administration, and leptin may transiently attenuate olanzapine-induced glucose intolerance.