Although atomoxetine, a selective norepinephrine reuptake inhibitor, is widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is limited data on its cytogenetic effects. This study aimed to investigate the cytotoxicity and genotoxicity of atomoxetine in vivo and silico. Chromosome aberration and micronucleus assays were used to analyze the genotoxic effect of atomoxetine in human peripheral blood lymphocytes under culture conditions. The mitotic index was assessed for cytotoxic potential. For the docking analysis, DNA receptor (1BNA) was prepared with ChimeraX, and the Atomoxetine molecule was optimized by Avogadro2.0 software. In silico molecular docking analysis was carried out utilizing SwissDock online platform. The results obtained were visualized using ChimeraX and Pymol software. Atomoxetine doses of 9.6 µg/mL (equal to about 1.2 mg/kg as a maintenance dose), 14.4 µg/mL (equal about to 1.8 mg/kg as the highest dose systematically tested), 48.0 µg/mL (equal about to 6 mg/kg as five times the maintenance dose) and 96.0 µg/mL (equal about to 12 mg/kg as ten times the maintenance dose) were analyzed. The findings clearly indicate that atomoxetine has no genotoxic effect at the therapeutic dose. However, we observed genotoxic effects at 48.0 and 96.0 µg/mL doses. No strong binding affinity occurs in silico analyses. As one of the initial inquiries into the in silico and in vivo appraisal of atomoxetine's genotoxic impacts, the research has established that atomoxetine does not significantly affect the frequency of chromosomal damage or micronucleus formation. Genotoxic effects should be kept in mind at doses above clinical practice.

L-DOPA-induced dyskinesia (LID) remains the most challenging complication of dopamine replacement therapy in Parkinson’s disease, correlated with maladaptive plasticity within corticostriatal circuits. Perineuronal nets (PNNs), extracellular matrix structures enwrapping mainly parvalbumin interneurons (PV-INs), are key regulators of neuronal stability and plasticity, yet their contribution to LID is unknown. Using a unilateral 6-hydroxydopamine rat model of Parkinsonism followed by chronic L-DOPA administration, we quantified PNN–PV associations by Wisteria floribunda agglutinin (WFA) and PV immunolabeling across striatal and motor cortical territories. Dopamine loss markedly reduced PNN density and intensity in the dorsolateral striatum (DLS), which only partially recovered after L-DOPA. In LID, canonical WFA⁺/PV⁺ cells remained low, whereas non-canonical WFA⁻/PV⁺ populations expanded in both DLS and M1 motor cortex (M1), indicating region-specific remodeling toward a high-plasticity state. To assess causality, we used Chondroitinase ABC (ChABC) for PNN degradation. DLS-targeted ChABC exacerbated abnormal involuntary movements and increased local PV density, while M1-ChABC had no behavioral effect but altered PV metrics within the DLS–M1 axis. These findings identify the DLS as a critical node where PNN fragility amplifies dyskinesia, highlight a functional coupling between striatal and cortical PNN–PV remodeling, and suggest that stabilizing extracellular matrix integrity could mitigate maladaptive plasticity underlying LID.

In this letter, we aimed to explore the prevalence, clinical features, etiological factors, and treatment responses of catatonia syndrome in patients with delirium. It will also reviewcurrent literature on the etiological and pathophysiological connections between delirium andcatatonia. The goal is to improve clinical awareness of catatonia in individuals with delirium.

Vortioxetine is a multimodal antidepressant with reported benefits on cognitive functioning, social functioning, and fatigue, however its potential genotoxic risks have not been adequately studied. Therefore, this study aims to investigate the cytotoxicity and genotoxicity of vortioxetine in vivo and in silico. Genotoxic effects were assessed using Chromosome aberration (CA) and micronucleus (MN) assays in cultured human peripheral blood lymphocyte. Cytotoxicity was evaluated through Mitotic index (MI), and DNA interaction was analysed by UV titration and agarose gel electrophoresis. In silico analyses were performed with Attraction Cavities and AutoDock Vina methods. Experimental results demonstrate that vortioxetine binds to Calf Thymus DNA (CT-DNA) through intercalative interactions and cleaves pBR322 DNA in the presence of hydrogen peroxide. DNA binding studies indicated that groove binding is the effective interaction between vortioxetine and CT-DNA (Kb: 6.25 × 10⁵ M^− 1). It was also supported by molecular docking results, where binding affinities of vortioxetine and escitalopram were − 7.29 and − 7.69 kcal/mol for Attracting Cavities and − 6.01 and − 6.57 kcal/mol for AutoDock Vina. When comparing vortioxetine to escitalopram, both drugs were found to be potentially genotoxic. These findings suggest a potential genotoxic risk with prolonged use and provide valuable insight for clinicians in evaluating long-term safety.