Current Neuropharmacology (Volume 24 - Issue 5)

Dealing with Early-Onset Schizophrenia and the Role of Lurasidone: An Expert Opinion

2026-04-07

Compared to schizophrenia in adults, Early Onset Schizophrenia (EOS) features diagnostic, clinical, and therapeutic peculiarities that are the subject of ongoing discussion among psychiatrists and neuropsychiatrists. This article presents the outcomes of a meeting and a series of virtual roundtable discussions among specialists who validated practical recommendations for the diagnosis and management of EOS in light of recent literature. The identification of risk factors and prodromal symptoms, as well as the differentiation of EOS from other psychiatric conditions, is crucial for early detection. Timely identification enables the implementation of appropriate psycho-behavioural and pharmacological interventions and supports close monitoring of the developmental trajectories associated with EOS. The collaboration between the different professionals who deal with EOS patients and a therapeutic approach that allows a normal cognitive, sexual, and psychophysical development makes it possible to ensure the therapeutic alliance necessary for the optimal management of the disease over time. In a scenario that is complicated by negative prognostic factors, such as the late recognition of the disease, comorbid and latent psychiatric conditions, the increasingly widespread use of substances among adolescents, and a poor therapeutic adherence often due to antipsychotics side effects, a growing body of literature emphasizes the advantages of lurasidone in the treatment of EOS. Compared to other pharmacological agents commonly used in schizophrenia, lurasidone has been shown to intervene comprehensively and effectively against the positive and negative symptoms of EOS, with manageable side effects and the preservation of a good QoL.

Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes

2026-04-07

Stroke patients often experience multiple functional impairments, including difficulties with swallowing, speech, cognition, and motor skills, which can lead to symptoms such as emotional distress and cognitive deficits. Approximately one-third of post-stroke patients may develop poststroke depression (PSD), significantly hindering recovery and increasing the burden on families and healthcare systems. This review focuses on the underlying mechanisms of PSD, emphasizing the glutamatergic hypothesis. As the primary excitatory neurotransmitter, glutamate plays a central role in neural-signaling. However, excessive glutamate accumulation can cause neuronal damage, making it a key mechanism in the development of PSD. Astrocytes are crucial for maintaining glutamate homeostasis by clearing excess glutamate and regulating its synthesis and transport, thereby preventing excitotoxicity. Following a stroke, astrocytic dysfunction—characterized by overactivation and inflammatory responses—can exacerbate neuronal injury and further contribute to the emergence of depressive symptoms. This article also highlights potential therapeutic approaches targeting the glutamatergic system, such as NMDA receptor antagonists, AMPA receptor antagonists, and modulators of glutamate transporters, as well as other types (e.g., Chinese medicine, herbal medicine, and targeted pathways acting on neurons). These strategies offer promising avenues for PSD treatment. Future studies should delve deeper into the molecular mechanisms by which astrocytes regulate glutamate homeostasis, providing a robust foundation for the precision treatment of post-stroke depression.

Resilience and Recalibration of Bibliometric Indicators in Neurosciences and Neuropharmacology Journals After COVID-19: A Longitudinal Rate of Change Analysis Using Mixed-Effects Models

2026-04-07

Introduction: The COVID-19 pandemic triggered unprecedented changes in the scholarly publishing landscape, particularly in biomedical fields such as Neurosciences and Neuropharmacology. Several journals experienced steep, short-term increases in citation metrics during 2020-2022. However, it remains uncertain whether these surges reflected a sustainable impact or temporary inflation. This study aimed to analyze post-pandemic bibliometric behavior by evaluating the Rate of Change (RoC) in key journal-level indicators from 2013 to 2023.

Methods: A retrospective longitudinal study was conducted on 233 neuroscience journals indexed in the Journal Citation Reports. Six indicators were analyzed: Journal Impact Factor (JIF), Eigenfactor Score, Immediacy Index, Article Influence Score, Cited Half-Life, and Total Citations. RoC was calculated for each metric on an annual basis. Mixed-effects models with random intercepts and slopes were constructed to evaluate longitudinal trajectories and identify changes associated with three defined periods: prepandemic (2013-2019), pandemic (2020-2022), and post-pandemic (2023). Subgroup analyses assessed journal quartiles and categories to explore variations in impact resilience.

Results: The pandemic period (2020-2022) showed significant increases in RoC for JIF (mean β = +4.85, p = 0.004), Immediacy Index (β = +6.22, p = 0.002), and Total Citations (β = +5.88, p < 0.001). These changes were more prominent in top-quartile journals and those classified under Neuropharmacology. In contrast, alternative metrics such as the Eigenfactor Score and Article Influence Score remained relatively stable across the same period. In 2023, most indicators exhibited a normalization trend, with JIF and Immediacy Index showing marked deceleration in RoC, suggesting a post-pandemic recalibration. Journals with sustained positive trajectories were primarily concentrated in high-impact clusters, with Current Neuropharmacology ranking among the top performers by RoC slope.

Discussion: The findings demonstrate that the surge in citations during the pandemic was primarily transitory and varied across bibliometric indicators. Traditional metrics like JIF and Immediacy Index were more sensitive to systemic shocks, while influence-based indicators (Eigenfactor and Article Influence Score) showed higher temporal resilience. The application of RoC allowed for a nuanced interpretation of metric trajectories and minimized misinterpretation of short-term spikes. Limitations include reliance on publicly available data and potential lag effects in citation behavior not fully captured within the 10-year window.

Conclusion: This study reveals that pandemic-era citation inflation in Neuroscience journals was largely temporary and metric-dependent. RoC-based modeling offers a reproducible and adaptable approach for assessing the sustainability of bibliometric trends. These insights can help editors, funders, and academic institutions better understand journal performance, make informed decisions about research dissemination, and refine metrics-based evaluation frameworks in the post-pandemic publishing environment.

Microglia-Neuron Interactions in Alzheimer’s Disease

2026-04-07

Alzheimer's disease (AD) is a progressive disease characterized by significant cognitive decline, posing a substantial threat to life. Neuronal loss and dysfunction are responsible for the cognitive decline and behavioral disturbances observed in AD. Microglia are increasingly recognized for shaping the fate of neurons. However, the role of microglia-neuron interaction in neuronal degeneration of AD remains largely unclear. This review discusses microglia-mediated excessive synaptic pruning and microglia-neuron metabolic coupling in the neuronal degeneration of AD. It also summarizes the role of microglia-neuron interactions in classical pathogenic hypotheses such as the amyloid cascade, tau protein, neuroinflammation, and metal ions. It is found that microglia can serve as protectors of neurons, yet they also exacerbate neuronal damage under stress stimulation. This bidirectional modulation of microglia-neuron interaction provides a novel direction for rescuing AD neurons.

Gut Microbiota and Bipolar Disorder: Advances in Translational Applications

2026-04-07

Bipolar disorder is a severe, recurrent affective disorder that imposes significant pain and burden on both the patients themselves and the social economy. Recent studies have indicated the involvement of intestinal flora in emotional regulation, as well as its close association with the occurrence and progression of diseases such as bipolar disorder. Therefore, conducting comprehensive research on the impact of intestinal microflora and the \"gut-brain axis\" on bipolar disorder becomes imperative, offering novel insights into its etiology, diagnosis, and treatment options. Consequently, this article provides an overview of the role and potential mechanisms underlying intestinal microbiota in bipolar disorder.

Protein Kinases in Alzheimer’s Disease: Pioneering Insights into Pathogenesis and Therapeutic Breakthroughs

2026-04-07

Alzheimer's Disease (AD) is an exhausting neurodegenerative condition marked by the build-up of abnormal protein aggregates in the brain and a progressive loss of cognitive function. The complicated role that protein kinases play in the pathophysiology of AD has come to light more and more in recent years. The symptoms of AD include memory loss, cognitive impairment, and neuronal malfunction. Many cellular processes, including synaptic plasticity, neuronal survival, and protein homeostasis, have been linked to protein kinases, a class of enzymes that control phosphorylation. The etiology of AD has been closely related to the dysregulation of protein kinases, including those implicated in the phosphorylation of tau and the formation of amyloid-beta. GSK-3, also known as glycogen synthase kinase, is one of the most studied protein kinases in Alzheimer's disease. It is known that GSK-3 phosphorylates tau protein, causing it to clump together and create neurofibrillary tangles. Moreover, GSK-3 activation increases the development of amyloid-beta, which furthers the disease's progression. Additional protein kinases, including Cyclin-Dependent Kinase 5 (CDK5) and calcium/calmodulin-dependent protein kinase II (CaMKII), have also been connected to tau phosphorylation and synaptic dysfunction in AD. Protein kinases play a crucial role in the pathophysiology of AD, extending beyond tau phosphorylation. Research has shown that Amyloid Precursor Protein (APP) processing is regulated by Protein Kinases A (PKA) and C (PKC), which affects the production and clearance of amyloid-beta. Furthermore, AD etiology involves oxidative stress, neuroinflammation, and mitochondrial dysfunction, all of which are regulated by protein kinases. This study will cover the effects of protein kinases in AD, focusing on their role in tau phosphorylation, an attribute of the disease. We will also address the role of protein kinase in the development of amyloid-beta, synaptic malfunction, and neuroinflammation.

Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-CD20 Monoclonal Antibodies for Multiple Sclerosis Treatment

2026-04-07

The therapeutic scenario for multiple sclerosis (MS) has expanded rapidly over the last few years. Among the available treatments, anti-CD20 monoclonal antibodies, including rituximab, ocrelizumab, ofatumumab, and ublituximab, have shown significant results in reducing disease activity and slowing progression, particularly in relapsing MS. The distinct mechanisms of action, including the pharmacokinetic and pharmacodynamic profiles as well as the immunogenicity of these drugs, require careful consideration to tailor treatment for individual patients. A comprehensive review of the literature was conducted by searching PubMed and evaluating key studies, trials, and congress abstracts related to the use of anti-CD20 monoclonal antibodies. The analysis focused on the pharmacokinetic and pharmacodynamic profiles, as well as the immunogenicity, of anti-CD20 therapies currently available, with particular emphasis on the recently approved ublituximab. Ocrelizumab is effective in both relapsing-remitting and primary-progressive MS, using antibodydependent cellular cytotoxicity (ADCC) as its primary mechanism of action, with intravenous and subcutaneous administration options ensuring flexible treatment delivery. Ofatumumab depletes B-cells through enhanced complement-dependent cytotoxicity, offering convenient monthly subcutaneous self-administration. Ublituximab’s unique glycoengineered fragment crystallizable region enhances ADCC, resulting in rapid B-cell depletion and potentially improving its safety profile. Ublituximab allows for a shorter infusion time without requiring post-infusion monitoring after the second dose, provided there have been no prior reactions. Understanding the characteristics of different anti-CD20 monoclonal antibodies is critical for optimizing treatment, enhancing patient outcomes, and minimizing treatment burden. Ublituximab represents a promising option, offering a shorter infusion time and higher ADCC activity, which complements existing treatments such as ocrelizumab and ofatumumab.

Neural Circuit Mechanisms of General Anaesthesia Induction: Current Advances and Future Directions

2026-04-07

General anaesthesia is traditionally divided into three distinct stages: induction, maintenance, and recovery. However, much of the existing literature has primarily focused on elucidating the mechanisms involved in the recovery phase, yielding several notable advancements. It is essential to recognize, however, that the induction and recovery phases represent two distinct processes. Studies in the induction phase have mainly centred on the impact of inhalational and intravenous anaesthetics on neural circuits, particularly those in the cortical and subcortical nuclei, as well as their specific effects on various neurotransmitters. Yet, the precise neural circuit mechanisms underlying anaesthetic induction still require further exploration. General anaesthetics influence neural circuitry by targeting neurons in particular nuclei, with their effects varying according to the distinct properties of individual anaesthetic agents. During the induction of anaesthesia, both the cortex and subcortical nuclei are significantly involved, with the inhibition of the subthalamic nucleus considered a core mechanism underlying this process. Notably, the periventricular thalamus, as part of the thalamus structure, holds particular importance in regulating the loss of consciousness. Additionally, the spinal cord and peripheral nervous system may play a potentially important role during the induction phase of general anaesthesia. Gaining a deeper understanding of the mechanisms underlying anaesthetic induction could reveal potential neuroanatomical targets that elucidate the alterations in consciousness during this phase of general anaesthesia. Such insights are invaluable in the quest for more effective, precise, and controllable anaesthetic practices, thereby enhancing the selection and combination of anaesthetic agents.

Assessment Value of Electromyography for Bortezomib-Related Peripheral Neuropathy

2026-04-07

Introduction: This study investigates the relationship between National Cancer Institute Common Terminology Criteria (NCI-CTC) for grading bortezomib-induced peripheral neuropathy (BIPN) and objective motor/sensory nerve dysfunctions assessed by nerve conduction studies (NCS). It also evaluates the correlation between specific nerve conduction abnormalities and progression- free survival (PFS).

Methods: Thirty-three patients with multiple myeloma developing peripheral neuropathy during bortezomib treatment were enrolled. Participants were grouped based on NCI-CTC toxicity scores (< 2, n=17; ≥ 2, n=16). Comprehensive NCS were performed, assessing compound muscle action potentials (CMAP), motor conduction velocities (MCV), sensory nerve action potentials (SNAP), and sensory conduction velocities (SCV) across ulnar, median, tibial, peroneal, sural, and superficial peroneal nerves. Correlation analyses were used to examine the association between NCS parameters and PFS.

Results: Patients with higher NCI-CTC grades (≥ 2) exhibited significant reductions in motor and sensory nerve conduction parameters. Notably, the peroneal nerve showed significant decreases in CMAP (p=0.0059) and MCV (p=0.0223). The superficial peroneal nerve displayed a significant reduction in SCV (p=0.0189). A strong positive correlation was found between median nerve SNAP and longer PFS (r=0.558, p=0.001).

Discussion: The findings indicate that higher clinical grades of BIPN (NCI-CTC ≥ 2) are associated with objective neurophysiological evidence of worsened nerve function, with the peroneal nerve being particularly affected. The correlation between median nerve SNAP and PFS suggests that NCS parameters could potentially serve as prognostic markers in patients with BIPN.

Conclusion: Bortezomib-induced neurotoxicity leads to significant impairments in both motor and sensory nerve conduction. Median nerve SNAP shows promise as a predictor for PFS, underscoring the potential value of NCS in monitoring neurotoxicity and guiding clinical management in patients receiving bortezomib.

Maternal Multiple Sclerosis and Offspring’s Developmental and Behavioral Profile: A Case-control Study

2026-04-07

Introduction: Maternal chronic immune and inflammatory conditions may predispose newborns to atypical developmental trajectories, identifying pregnancy as a key period for the etiopathogenesis of neurodevelopmental disorders. The possible long-term impact of maternal multiple sclerosis (MS) on the offspring’s cognitive and behavioral development and its pharmacological treatment during pregnancy is mostly unknown. This study aims to delineate the cognitive and behavioral profile of offsprings exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, in comparison to a control group.

Methods: We retrospectively enrolled 39 children (23 males; 16 females; mean age 45.82 ± 35.46 months) exposed to maternal MS, untreated or treated with Natalizumab throughout pregnancy, and 36 children (24 males; 12 females, mean age 38.03 ± 21.52 months) of healthy mothers. All offspring underwent a standardized evaluation of their intellectual or developmental quotient, adaptive functioning, and behavioral issues, including symptoms of autism.

Results: The clinical profile of the included offspring was characterized by an adequate cognitive profile and a good level of adaptive skills (MS offspring: Griffiths III mean total DQ (N = 30) 114.57; WISC-IV mean Full IQs (N= 9) 115.44; mean ABAS GAC 97.28/Control offspring: Griffiths III mean total DQ (N = 31) 105.42; WISC-IV mean Full IQs (N= 4) 119.25 ± 11.32; mean ABAS GAC 97.82 ± 21.4). Furthermore, no significant behavioural problems or autism symptoms emerged in the entire group, regardless of MS treatment.

Conclusion: Offspring's developmental and behavioral phenotypes do not appear to be influenced by maternal treatment with Natalizumab until late pregnancy, nor by maternal variables directly related to MS (age at the time of MS diagnosis, disease duration, and severity).

Experimental Evaluation of QY-69: A Butyrylcholinesterase Inhibitor with Anti-Glioblastoma Efficacy

2026-04-07

Introduction: Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, characterized by poor prognosis. Moreover, cognitive impairment from the tumor and its treatments compromises patients' quality of life. Butyrylcholinesterase (BChE) inhibition enhances cognitive function. Notably, BCHE is overexpressed in GBM tissues; its downregulation suppresses tumor cell proliferation, migration, and invasion. This study aimed to identify a BChE inhibitor with dual functionality: anti-GBM efficacy and cognitive protection via modulation of neuroinflammation.

Methods: QY-69 was identified from an in-house BChE inhibitor library through cytotoxicity-based screening. Its anti-GBM effects were evaluated through colony formation, wound healing, and transwell assays. Orthotopic GBM mice were treated with QY-69 orally for 15 days. Tumor progression, cognitive function (Morris water maze), and neuroinflammation (microglia and astrocyte immunofluorescence) were analyzed.

Results: QY-69 exhibited significant antiproliferative activity at micromolar concentrations. In vitro assays demonstrated significant inhibition of GBM cell growth, migration, and invasion. Behavioral impairment in mice was improved, and the activation of astrocytes and microglia in peritumoral tissues was reduced, indicating a decrease in neuroinflammation.

Discussion: QY-69 demonstrated dual therapeutic potential in GBM by inhibiting tumor progression and alleviating cognitive impairment. However, its precise molecular mechanisms remain to be elucidated. Future research should employ transcriptomic and proteomic approaches to elucidate the molecular basis of its anti-GBM activity.

Conclusion: QY-69, a BChE inhibitor, exhibits potent anti-GBM activity and confers cognitive protection, positioning it as a promising dual-action therapeutic candidate. By inhibiting tumor progression and reducing neuroinflammation, it may enhance both survival and quality of life in GBM patients.

Delivery of Nerve Growth Factor via Exosome Attenuates Neuropathic Pain in a Rat Model of Chronic Constriction Injury

2026-04-07

Introduction: The nerve growth factor (NGF) is a crucial neurotrophic factor with the ability to induce neuronal differentiation. However, whether NGF-loaded exosomes (Exo-NGF) can alleviate neuropathic pain in chronic constriction injury (CCI) rats remains unclear.

Methods: A neuropathic pain model was established using CCI rats. The pain was assessed using the von Frey test and the hot plate test. Exo-NGF was collected from HEK293 cells transfected with an NGF plasmid. The diameter of Exo-NGF was determined using transmission electron microscopy. Protein levels of inflammatory factors, including IL-18, IL-1β, and TNF-α, were measured using enzyme- linked immunosorbent assay, and their mRNA levels were evaluated using qPCR. The NODlike receptor family pyrin domain-containing protein 3 (NLRP3) protein levels were determined using immunostaining and Western blot.

Results: NGF protein and mRNA were highly expressed in Exo-NGF. The mRNA in Exo-NGF was successfully delivered into neural stem cells and promoted their differentiation. Injection of Exo- NGF into the spinal dorsal horn significantly alleviated mechanical allodynia and thermal hyperalgesia. Additionally, Exo-NGF reduced levels of IL-18, IL-1β, and TNF-α. NLRP3 and its key components, including apoptosis-associated speck-like protein and caspase-1, were also reduced by Exo- NGF treatment in CCI rats.

Discussion: Our findings highlight the therapeutic potential of exosome-based NGF delivery for treating chronic pain conditions.

Conclusion: Exo-NGF significantly alleviates neuropathic pain by suppressing inflammation and NLRP3 activation.