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Journal = Brain Sciences
Section = Neuropharmacology and Neuropathology

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31 pages, 638 KiB  
Systematic Review
Exploring the Autistic Brain: A Systematic Review of Diffusion Tensor Imaging Studies on Neural Connectivity in Autism Spectrum Disorder
by Giuseppe Marano, Georgios D. Kotzalidis, Maria Benedetta Anesini, Sara Barbonetti, Sara Rossi, Miriam Milintenda, Antonio Restaino, Mariateresa Acanfora, Gianandrea Traversi, Giorgio Veneziani, Maria Picilli, Tommaso Callovini, Carlo Lai, Eugenio Maria Mercuri, Gabriele Sani and Marianna Mazza
Brain Sci. 2025, 15(8), 824; https://doi.org/10.3390/brainsci15080824 - 31 Jul 2025
Viewed by 405
Abstract
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article
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14 pages, 689 KiB  
Systematic Review
The Effect of Mental Health First Aid Training on Pharmacist and Pharmacy Student Confidence and Knowledge: A Systematic Review and Meta-Analysis
by David Frond, Shannon Habba, Brittany Stewart and Kyle J. Burghardt
Brain Sci. 2025, 15(8), 816; https://doi.org/10.3390/brainsci15080816 - 29 Jul 2025
Viewed by 355
Abstract
Background/Objectives: Pharmacists are highly accessible healthcare providers who have frequent, repeated contact with diverse patient populations. They are poised to offer expanded and comprehensive healthcare, including mental health services. One potential barrier to this is a lack of knowledge, confidence, or training in [...] Read more.
Background/Objectives: Pharmacists are highly accessible healthcare providers who have frequent, repeated contact with diverse patient populations. They are poised to offer expanded and comprehensive healthcare, including mental health services. One potential barrier to this is a lack of knowledge, confidence, or training in mental health, which may be overcome with a program like Mental Health First Aid (MHFA) training. The aim of this systematic review and meta-analysis is to fill this gap in knowledge by critically evaluating all studies of MHFA training for pharmacists or pharmacy students that report on knowledge, attitudes, or self-efficacy outcomes. Methods: A systematic review was performed to identify all relevant studies. Data was extracted and a random-effects meta-analysis was performed for knowledge and attitudes/self-efficacy outcomes, respectively. Subgroup analyses were performed based on survey question type, geographic location, and population studied. Results: Overall, MHFA training significantly increased pharmacists’ and pharmacy students’ knowledge (Hedges’ g = 0.228) and combined attitudinal/self-efficacy measures (Hedges’ g = 0.376). Subgroup analyses based on question type, study quality, design, population studied, and location showed similar, significant effects. Conclusions: MHFA training appears to have significant effects on pharmacist and pharmacy student knowledge, attitudes, and self-efficacy. Future work should establish the durability of these effects. Full article
(This article belongs to the Special Issue Pharmacy and Mental Health)
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18 pages, 4065 KiB  
Article
Age-Related Changes in Neuroinflammation and Epigenetic Regulation in Mouse Ischemic Stroke Model
by Mari Kondo, Hayato Tamura, Eri Segi-Nishida and Hiroshi Hasegawa
Brain Sci. 2025, 15(8), 810; https://doi.org/10.3390/brainsci15080810 - 28 Jul 2025
Viewed by 384
Abstract
Background/Objectives: The incidence and prevalence of ischemic stroke, a leading cause of death and disability worldwide, are significantly higher in older adults than in younger individuals. Senescence induces a variety of biological changes that influence the pathogenesis of diseases such as ischemic [...] Read more.
Background/Objectives: The incidence and prevalence of ischemic stroke, a leading cause of death and disability worldwide, are significantly higher in older adults than in younger individuals. Senescence induces a variety of biological changes that influence the pathogenesis of diseases such as ischemic stroke, thereby necessitating age-specific medical treatments. However, the molecular mechanisms underlying age-related differences in ischemic stroke progression remain poorly understood. Methods: We compared the histological and molecular features of ischemic stroke in a photothrombotic mouse model, focusing on 9-week-old (young) and 90-week-old (old) mice. Results: We found that microglial accumulation at the infarct region of the cerebral cortex was significantly lower in old mice than in young ones. This reduction in the microglial response was accompanied by a decrease in the morphological robustness of the astrocytes forming the glial scar. Furthermore, the mRNA expression of proinflammatory cytokines CXCL10, CCL2, and TNF-α, which were upregulated in the infarct region, was considerably higher in the old mice than in the young ones. Cytokine expression was well correlated with the mRNA levels of Toll-like receptor 4 (TLR4), a key regulator of neuroinflammation in old mice, but less correlated with them in young mice. Interestingly, Tlr4 mRNA expression in young mice was negatively correlated with the mRNA expression of the epigenetic regulator HDAC7, whereas this correlation was positive in old mice. Conclusions: These findings suggest that age-dependent changes in epigenetic regulation, such as the interaction between HDAC7 and TLR4, may contribute to the distinct pathological progression of ischemic stroke in older individuals. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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29 pages, 646 KiB  
Systematic Review
Connected by Boredom: A Systematic Review of the Role of Trait Boredom in Problematic Technology Use
by Ginevra Tagliaferri, Manuel Martí-Vilar, Francesca Valeria Frisari, Alessandro Quaglieri, Emanuela Mari, Jessica Burrai, Anna Maria Giannini and Clarissa Cricenti
Brain Sci. 2025, 15(8), 794; https://doi.org/10.3390/brainsci15080794 - 25 Jul 2025
Viewed by 734
Abstract
Background/Objectives: In an increasingly pervasive digital environment, trait boredom has been identified as a key psychological factor in the onset and maintenance of problematic digital technology use. This systematic review aims to investigate the role of trait boredom in digital behavioral addictions, including [...] Read more.
Background/Objectives: In an increasingly pervasive digital environment, trait boredom has been identified as a key psychological factor in the onset and maintenance of problematic digital technology use. This systematic review aims to investigate the role of trait boredom in digital behavioral addictions, including problematic smartphone use, Internet and social media overuse, and gaming addiction, through theoretical models such as the I-PACE model and the Compensatory Internet Use Theory (CIUT). Methods: A systematic literature search was conducted across multiple scientific databases (PsycINFO, Web of Science, PubMed, and Scopus), yielding a total of 4603 records. Following the PRISMA guidelines after duplicate removal and screening based on title and abstract, 152 articles were assessed for full-text eligibility, and 28 studies met the predefined inclusion and exclusion criteria and were included in the final review. Results: Findings reveal that trait boredom functions as both a direct and indirect factor in problematic technology use. It serves as a mediator and moderator in the relationship between psychological vulnerabilities (e.g., depression, alexithymia, vulnerable narcissism) and dysfunctional digital behaviors. Furthermore, as an independent variable, it has an influence on technological variables through Fear of Missing Out (FoMO), loneliness, low self-regulation, and dysfunctional metacognitions, while protective factors such as mindfulness and attentional control mitigate its impact. Conclusions: Boredom represents a central psychological lever for understanding behavioral addictions in the digital age and should be considered a key target in preventive and therapeutic interventions focused on enhancing self-regulation and meaningful engagement with free time. Full article
(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)
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31 pages, 3963 KiB  
Review
Neuroglobin and Cytoglobin in Mammalian Nervous Systems: About Distribution, Regulation, Function, and Some Open Questions
by Stefan Reuss
Brain Sci. 2025, 15(8), 784; https://doi.org/10.3390/brainsci15080784 - 23 Jul 2025
Viewed by 463
Abstract
Globins are a class of globular proteins that function in the transportation or storage of oxygen. They are critical for cellular metabolism. Notable examples include hemoglobin, which is found in red blood cells, and myoglobin, which is present in muscle cells. Approximately two [...] Read more.
Globins are a class of globular proteins that function in the transportation or storage of oxygen. They are critical for cellular metabolism. Notable examples include hemoglobin, which is found in red blood cells, and myoglobin, which is present in muscle cells. Approximately two decades ago, a third globin, designated as neuroglobin, was identified, expressed predominantly in neuronal cells. This was followed two years later by the fourth, cytoglobin, found in cells of the fibroblast lineage, as well as in neuronal cell populations of the central and nervous systems. Both neuroglobin and cytoglobin have been found in the sensory and endocrine systems, albeit inconsistently, and it is thought that they are engaged in functions such as oxygen transport and storage, scavenging of free radicals, NO metabolism, peroxidase activity, and signaling functions. Neuroglobin is also expressed in astrocytes under challenging conditions. Common neuroscience methods were utilized to study the distribution and regulation of globin tissues and of single brain cells. Despite considerable overlap in the findings of various studies, some results deviate significantly from other studies. The potential causes of these discrepancies may include variations in detection methods, animal age and sex, time of day and year, and differing cell culture conditions. This review will explore factors that may influence functional aspects of globins and their detection in the mammalian brain. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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10 pages, 232 KiB  
Article
Symptom-Triggered Alcohol Detoxification Compared to Fixed-Dose Regimen of Benzodiazepines: A Retrospective Case–Control Study
by Laurent Becciolini, Fabienne Wehrli, Jens Kronschnabel, Carolina Wiesendanger, Norbert Scherbaum and Patrik Roser
Brain Sci. 2025, 15(7), 758; https://doi.org/10.3390/brainsci15070758 - 17 Jul 2025
Viewed by 359
Abstract
Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to [...] Read more.
Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to evaluate the effectiveness and safety of STT using the Hamburg Alcohol Withdrawal Scale (HAES) compared to FDRs in the management of inpatient alcohol detoxification. Methods: In a retrospective case–control study, alcohol detoxification treatment in STT was compared with FDRs. During a twelve-month observation period, a total of 123 patients in the STT group were recruited and compared with 123 controls in the FDR group (matched according to sex, age, and current amount of alcohol consumption) treated in the same hospital before the implementation of STT. The study outcomes included the total benzodiazepine dosage, duration of acute detoxification phase, length of inpatient stay, and occurrence of complications such as epileptic seizures and delirium tremens. Results: STT showed a significantly lower total benzodiazepine dosage (22.50 mg vs. 115.00 mg, p < 0.001), a shorter duration of the detoxification phase (48.00 h vs. 201.75 h, p < 0.001), and a reduced length of inpatient stay (23.00 days vs. 28.00 days, p = 0.003) compared to FDRs. There were no significant differences in the rates of complications between the two settings. Linear mixed model analysis revealed that the differences remained highly significant even after adjusting for various explanatory variables (i.e., age, sex, standard units of alcohol, psychiatric comorbidities, treatment discontinuation, and occurrence of any complication). Conclusions: STT appears to be as effective and safe as traditional fixed-dose regimens of benzodiazepines for the management of inpatient alcohol detoxification. This approach may thereby minimize unnecessary pharmacological exposure, facilitate the earlier integration of patients into psychoeducational and psychosocial interventions, and reduce healthcare costs. Full article
(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)
13 pages, 505 KiB  
Review
Sphenopalatine Ganglion Blocks in Headache Management: A Review
by Andrei Lyle Bautista, Killian Coyne, Alexander Bautista and Alaa Abd-Elsayed
Brain Sci. 2025, 15(7), 672; https://doi.org/10.3390/brainsci15070672 - 22 Jun 2025
Viewed by 1084
Abstract
Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of [...] Read more.
Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of patients remain refractory or intolerant to these therapies. The sphenopalatine ganglion (SPG), a parasympathetic neural structure in the pterygopalatine fossa, is increasingly recognized as a critical node in the pathophysiology of primary headache disorders. SPG blocks—using local anesthetics, neurolytic agents, or electrical neuromodulation—offer a minimally invasive therapeutic approach by disrupting nociceptive transmission and autonomic activation. This narrative review synthesizes the anatomical and physiological rationale for SPG intervention, details various procedural techniques, evaluates clinical evidence across headache subtypes, and explores future research directions. Conditions covered include migraine, cluster headache, tension-type headache, trigeminal neuralgia, and persistent idiopathic facial pain. With expanding evidence and evolving technologies, SPG-targeted interventions have the potential to reshape the management of refractory headaches and facial pain syndromes. Full article
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15 pages, 808 KiB  
Article
Effect of Safinamide on Non-Motor Symptoms and Quality of Life in Parkinson’s Disease Patients According to Sex, Age, Disease Duration and Levodopa Equivalent Daily Dose
by Ángela Solleiro Vidal, Rosa Yáñez Baña, Carmen Labandeira Guerra, Maria Icíar Cimas Hernando, Iria Cabo López, Jose Manuel Paz González, Maria Gema Alonso Losada and Diego Santos García
Brain Sci. 2025, 15(7), 666; https://doi.org/10.3390/brainsci15070666 - 20 Jun 2025
Viewed by 799
Abstract
Background and objective: Safinamide can improve the non-motor symptoms (NMSs) and quality of life (QoL) in patients with Parkinson’s disease (PD). In this post hoc analysis of the SAFINONMOTOR study, we analyzed the effect of safinamide on NMSs and QoL according to age, [...] Read more.
Background and objective: Safinamide can improve the non-motor symptoms (NMSs) and quality of life (QoL) in patients with Parkinson’s disease (PD). In this post hoc analysis of the SAFINONMOTOR study, we analyzed the effect of safinamide on NMSs and QoL according to age, sex, disease duration (DD), and levodopa equivalent daily dose (LEDD). Patients and Methods: The change from baseline to the end of the observational period (6 months) in the Non-Motor Symptoms Scale (NMSS) and the 39-item Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) was analyzed in subgroups according to sex (male vs. female), age (≤75 vs. >75 years old), DD (≤10 vs. >10 years) and LEDD (≤1000 vs. >1000 mg). Nonparametric tests and general linear model (GLM) repeated measures were applied. Results: A total of 44 patients completed the final visit and were valid for the analysis. A significant reduction in the NMSS score was observed in all groups. Regarding QoL, a significant reduction in the PDQ-39 score was observed in females (p < 0.0001) and in patients with a DD > 10 years (p = 0.011) but not in males or those > 75 years old or receiving an LEDD > 1.000 mg. In the GLM, only LEDD at baseline influenced the degree of change in the NMSS total score (p = 0.026; F = 5.23). None of the variables influenced the change in the PDQ39. Conclusions: Safinamide improved NMSs independently of sex, age, DD, and LEDD. QoL improved independently of DD, and in females and non-elderly and very treated patients. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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13 pages, 4782 KiB  
Case Report
Anti-Ri Paraneoplastic Neurological Syndrome Presenting with Ocular Flutter in a Patient with Breast Cancer
by Francesca Cascone, Federica Stella, Christian Barbato, Antonio Minni and Giuseppe Attanasio
Brain Sci. 2025, 15(6), 628; https://doi.org/10.3390/brainsci15060628 - 11 Jun 2025
Viewed by 712
Abstract
Ocular flutter is an uncommon ophthalmic finding that may indicate paraneoplastic phenomena, and it is clinically characterized by intermittent bursts of conjugate, horizontal saccades without an intersaccadic interval. Ocular flutter must be differentiated from opsoclonus, which, although also characteristic of certain paraneoplastic syndromes, [...] Read more.
Ocular flutter is an uncommon ophthalmic finding that may indicate paraneoplastic phenomena, and it is clinically characterized by intermittent bursts of conjugate, horizontal saccades without an intersaccadic interval. Ocular flutter must be differentiated from opsoclonus, which, although also characteristic of certain paraneoplastic syndromes, is instead defined by multidirectional saccades on both the horizontal and vertical planes. This report describes a very rare presentation of anti-Ri syndrome in a patient with an undiagnosed breast cancer, presenting with ocular flutter, dizziness, blurred vision, photophobia, and vomiting. Comprehensive evaluations, including contrast-enhanced brain Magnetic Resonance Imaging (MRI), brain Computed Tomography (CT) scan, ophthalmological assessment, viral serology, complete blood count and thyroid, renal coagulation, hepatic function assessments, vitamin D and B12 levels, were all normal. Upon excluding other potential etiologies for the neurological symptoms, a paraneoplastic origin was considered. Serological tests confirmed the presence of anti-Ri onconeural antibodies, and a whole-body CT scan identified nodules in the right breast. Despite surgical excision of the primary tumor and subsequent medical therapy, there was no improvement in the neurological symptoms. Follow-up evaluations at 2 months, 6 months, 1 year and 2 years revealed persistent vestibular and neurological symptoms, with serum tests remaining positive for anti-Ri antibodies and no clinical or radiological evidence of neoplastic recurrence. Full article
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27 pages, 612 KiB  
Systematic Review
Cocaine Cues Used in Experimental Research: A Systematic Review
by Eileen Brobbin, Natalie Lowry, Matteo Cella, Alex Copello, Simon Coulton, Jerome Di Pietro, Colin Drummond, Steven Glautier, Ceyda Kiyak, Thomas Phillips, Daniel Stahl, Shelley Starr, Lucia Valmaggia, Colin Williams and Paolo Deluca
Brain Sci. 2025, 15(6), 626; https://doi.org/10.3390/brainsci15060626 - 10 Jun 2025
Viewed by 1375
Abstract
Aims: Cue exposure therapy (CET) is a promising treatment approach for cocaine substance use disorder (SUD). CET specifically targets the psychological and physiological responses elicited by drug-related cues, aiming to reduce their motivational impact. To advance understanding of CET for cocaine treatment, [...] Read more.
Aims: Cue exposure therapy (CET) is a promising treatment approach for cocaine substance use disorder (SUD). CET specifically targets the psychological and physiological responses elicited by drug-related cues, aiming to reduce their motivational impact. To advance understanding of CET for cocaine treatment, this systematic review aims to categorise the range of cocaine cues used in research. Methods: A systematic review of the existing literature with searches conducted on PubMed and Web of Science bibliographic databases with no time constraints in August 2024 (PROSPERO: CRD42024554361). Three reviewers were independently involved in the screening, review and data extraction process, in line with PRISMA guidelines. Data extracted included participant demographics, study design, data on the cocaine cue task, and examples (if provided). Each study was appraised and received a quality score. The secondary outcome was to summarise examples for each category type identified. The data are presented as a narrative synthesis. Results: 3600 articles were identified and screened. 235 articles were included in the analysis. Cues identified included images, paraphernalia, drug-related words, cocaine smell, auditory stimuli presented via audiotapes, video recordings, scripts, and virtual reality environments, often combining multiple modalities. Included studies recruited cocaine-dependent individuals, recreational users, polydrug users, and non-cocaine-using controls. The sample sizes of the studies ranged from a single case study to a study including 1974 participants. Conclusions: This review found that studies employed a wide range of cue categories, but detailed examples were often lacking, limiting replication. The number and combination of cues varied: some studies used only cocaine-related images, while others included images, videos, physical items, and audiotapes. The level of immersion and personalisation also differed considerably. All studies used cocaine-specific cues, most commonly images or representations of cocaine substance, cocaine use or drug paraphernalia, drug preparation items, or conversations of cocaine use and its effects. The overall quality of the included studies was deemed good, with all adhering to standard research norms. While this review highlights the breath of cue types used in the literature, further research should focus on enhancing cue exposure techniques by incorporating more immersive and personalised stimuli, and by providing clearer documentation of cue characteristics to support replication and clinical translation. Full article
(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)
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13 pages, 592 KiB  
Article
Prenatal Planning and Breastfeeding: Buffering Postpartum Depression Through Positive Affect
by Ana Catala, Cecilia Peñacoba and Patricia Catalá
Brain Sci. 2025, 15(6), 591; https://doi.org/10.3390/brainsci15060591 - 29 May 2025
Viewed by 470
Abstract
Background/Objectives: In the context of maternal mental health, this cross-sectional study investigates a moderated mediation model to explore how prenatal planning is associated with postpartum depression. Specifically, we examined whether planned pregnancy (X) is associated with fewer postpartum depression symptoms (Y) through greater [...] Read more.
Background/Objectives: In the context of maternal mental health, this cross-sectional study investigates a moderated mediation model to explore how prenatal planning is associated with postpartum depression. Specifically, we examined whether planned pregnancy (X) is associated with fewer postpartum depression symptoms (Y) through greater positive affect (M), and whether the indirect association is moderated by breastfeeding duration (W). Methods: Data were collected from 117 postpartum mothers via self-report questionnaires that measured the degree of pregnancy planning, positive affect, postpartum depression symptoms, and breastfeeding duration. Bootstrap analyses were performed to assess the conditional indirect effects across two levels of breastfeeding duration. Results: The findings suggest an indirect association between pregnancy planning and postpartum depressive symptoms through positive affect, moderated by breastfeeding duration. This association was statistically significant only among mothers who breastfed for less than six months, indicating that the protective emotional effect of pregnancy planning may be more evident in this group. No significant indirect effects were observed in mothers who breastfed beyond this duration. Conclusions: These exploratory findings suggest that positive affect may be a pathway through which prenatal planning relates to maternal well-being, particularly in the context of breastfeeding practices. Given the cross-sectional design, causal inferences cannot be drawn. Future longitudinal research is needed to confirm these associations. Full article
(This article belongs to the Special Issue Stress, Resilience and Susceptibility)
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27 pages, 6846 KiB  
Article
Chronic Stress Modulates Microglial Activation Dynamics, Shaping Priming Responses to Subsequent Stress
by Junyu Chen, Jiacheng Huang, Taolei Han and Nobuhiko Kojima
Brain Sci. 2025, 15(5), 534; https://doi.org/10.3390/brainsci15050534 - 21 May 2025
Viewed by 1335
Abstract
(1) Background: The high recurrence rate and individual differences in stress susceptibility contribute to the diverse symptoms of depression, making full recovery and relapse prevention challenging. Emerging evidence suggests that fluctuations in microglial activity are closely linked to depression progression under chronic stress [...] Read more.
(1) Background: The high recurrence rate and individual differences in stress susceptibility contribute to the diverse symptoms of depression, making full recovery and relapse prevention challenging. Emerging evidence suggests that fluctuations in microglial activity are closely linked to depression progression under chronic stress exposure. Changes in the brain microenvironment can elicit microglial priming, enhancing their sensitivity to external stimuli. However, few studies have longitudinally examined how microglial characteristics evolve throughout depression progression. (2) Methods: In this study, we investigated microglial morphological changes and their responses to acute stress at different stages of depression using the chronic unpredictable mild stress (CUMS) paradigm in mice. (3) Results: Our findings reveal that in the dentate gyrus, microglial activation indices, including cell number and morphology, exhibit distinct dynamic patterns depending on CUMS exposure duration. Notably, after 2 and 4 weeks of CUMS exposure followed by acute stress re-exposure, microglia display opposing response patterns. In contrast, after 6 weeks of CUMS exposure, primed microglia exhibit dysfunction, failing to respond to acute stress. Notably, depressive behaviors are not prominent after 2 weeks of CUMS exposure but become more pronounced after 4 and 6 weeks of exposure. Additionally, regardless of CUMS duration, body weight demonstrates an intrinsic capacity to normalize after stress cessation. (4) Conclusions: These findings suggest that microglial priming responses are state-dependent, either enhancing or suppressing secondary stimulus responses, or exceeding physiological limits, thereby preventing further activation. This study provides novel insights into the role of microglial priming in stress vulnerability and its contribution to depression progression. Full article
(This article belongs to the Special Issue Stress, Resilience and Susceptibility)
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24 pages, 641 KiB  
Article
Partner-Inflicted Brain Injury: Intentional, Concurrent, and Repeated Traumatic and Hypoxic Neurologic Insults
by Julianna M. Nemeth, Clarice Decker, Rachel Ramirez, Luke Montgomery, Alice Hinton, Sharefa Duhaney, Raya Smith, Allison Glasser, Abigail (Abby) Bowman, Emily Kulow and Amy Wermert
Brain Sci. 2025, 15(5), 524; https://doi.org/10.3390/brainsci15050524 - 19 May 2025
Viewed by 1108
Abstract
(1) Background: Traumatic brain injury (TBI) is caused from rapid head acceleration/deceleration, focal blows, blasts, penetrating forces, and/or shearing forces, whereas hypoxic–anoxic injury (HAI) is caused through oxygen deprivation events, including strangulation. Most service-seeking domestic violence (DV) survivors have prior mechanistic exposures that [...] Read more.
(1) Background: Traumatic brain injury (TBI) is caused from rapid head acceleration/deceleration, focal blows, blasts, penetrating forces, and/or shearing forces, whereas hypoxic–anoxic injury (HAI) is caused through oxygen deprivation events, including strangulation. Most service-seeking domestic violence (DV) survivors have prior mechanistic exposures that can lead to both injuries. At the time of our study, some evidence existed about the exposure to both injuries over the course of a survivor’s lifetime from abuse sources, yet little was known about their co-occurrence to the same survivor within the same episode of physical intimate partner violence (IPV). To better understand the lived experience of service-seeking DV survivors and the context in which partner-inflicted brain injury (PIBI) is sustained, we sought to understand intentional brain injury (BI) exposures that may need to be addressed and accommodated in services. Our aims were to 1. characterize the lifetime co-occurrence of strangulation and intentional head trauma exposures from all abuse sources to the same survivor and within select physical episodes of IPV and 2. establish the lifetime prevalence of PIBI. (2) Methods: Survivors seeking DV services in the state of Ohio in the United States of America (U.S.) completed interview-administered surveys in 2019 (n = 47). Community-based participatory action approaches guided all aspects of the study development, implementation, and interpretation. (3) Results: The sample was primarily women. Over 40% reported having Medicaid, the government-provided health insurance for the poor. Half had less than a postsecondary education. Over 80% of participants presented to DV services with both intentional head trauma and strangulation exposures across their lifetime from intimate partners and other abuse sources (i.e., child abuse, family violence, peer violence, sexual assault, etc.), though not always experienced at the same time. Nearly 50% reported an experience of concurrent head trauma and strangulation in either the first or last physical IPV episode. Following a partner’s attack, just over 60% reported ever having blacked out or lost consciousness—44% experienced a loss of consciousness (LOC) more than once—indicating a conservative estimate of a probable brain injury by an intimate partner. Over 80% of service-seeking DV survivors reported either a LOC or two or more alterations in consciousness (AICs) following an IPV attack and were classified as ever having a partner-inflicted brain injury. (4) Conclusions: Most service-seeking IPV survivors experience repetitive and concurrent exposures to abusive strangulation and head trauma through the life course and by intimate partners within the same violent event resulting in brain injury. We propose the use of the term partner-inflicted brain injury (PIBI) to describe the physiological disruption of normal brain functions caused by intentional, often concurrent and repeated, traumatic and hypoxic neurologic insults by an intimate partner within the context of ongoing psychological trauma, coercive control, and often past abuse exposures that could also result in chronic brain injury. We discuss CARE (Connect, Acknowledge, Respond, Evaluate), a brain-injury-aware enhancement to service delivery. CARE improved trauma-informed practices at organizations serving DV survivors because staff felt knowledgeable to address and accommodate brain injuries. Survivor behavior was then interpreted by staff as a “can’t” not a “won’t”, and social and functional supports were offered. Full article
(This article belongs to the Special Issue Shedding Light on the Hidden Epidemic of Violence and Brain Injury)
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14 pages, 1322 KiB  
Article
Examination of Psychotropic Medication Use Following Outpatient Behavioral Assessment and Treatment
by Maria G. Valdovinos, Melissa Trites and Janelle Ausenhus
Brain Sci. 2025, 15(5), 513; https://doi.org/10.3390/brainsci15050513 - 17 May 2025
Viewed by 573
Abstract
Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, [...] Read more.
Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, six months after the assessment, and a later follow-up time point (mean 25 months following the six-month time point, range 1 month to 41 months) were evaluated via a chart review. Alterations in psychotropic medication use were grouped into eight categories according to the type of medication change experienced. Care providers also completed a social validity survey rating their satisfaction with the assessment and interventions developed for their child. Results: This retrospective study revealed that children in this sample were more likely to experience starting a new medication and increases in the dose of psychotropic medication as time passed. Children were also less likely to remain on the same regimen of psychotropic medication as when they were first seen in the clinic. Additionally, although caregivers generally rated their experiences and outcomes with the behavioral clinic as favorable, additions and increases to psychotropic medication regimens still occurred. Conclusions: These findings are consistent with other reports of continued and increased prescribing of psychotropic medication across time in children with neurodevelopmental disorders, however, the results must be interpreted with caution given the small sample size which limits generalizability of these findings. Additionally, the lack of follow-up with the patients in this sample made it difficult to correlate changes in challenging behavior with psychotropic medication prescribing. Full article
(This article belongs to the Special Issue Advances in Psychopharmacology in Neurodevelopmental Disorders (NDDs))
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13 pages, 1252 KiB  
Article
Effectiveness and Safety of CGRP-Targeted Therapies Combined with Lifestyle Modifications for Chronic Migraine in Korean Pediatric Patients: A Retrospective Study
by Ji-Hoon Na, Hayoon Jeon, Ji-Eun Shim, Hyunjoo Lee and Young-Mock Lee
Brain Sci. 2025, 15(5), 493; https://doi.org/10.3390/brainsci15050493 - 8 May 2025
Cited by 2 | Viewed by 926
Abstract
Background/Objectives: Pediatric chronic migraine (CM) is a debilitating condition with challenging management due to diagnostic complexities and a lack of evidence-based treatment. Calcitonin gene-related peptide (CGRP)-targeted therapies have transformed adult CM management, but their use in pediatric populations is underexplored. This study evaluated [...] Read more.
Background/Objectives: Pediatric chronic migraine (CM) is a debilitating condition with challenging management due to diagnostic complexities and a lack of evidence-based treatment. Calcitonin gene-related peptide (CGRP)-targeted therapies have transformed adult CM management, but their use in pediatric populations is underexplored. This study evaluated the safety and efficacy of CGRP-targeted therapies combined with structured lifestyle modifications in Korean pediatric patients with CM. Methods: This retrospective study examined 10 pediatric CM patients treated at Gangnam Severance Hospital from 2021 to 2024. Inclusion criteria were as follows: (1) Pediatric Migraine Disability Assessment Scale (PedMIDAS) score ≥ 30, (2) >2 failed preventive therapies, and (3) ≥8 migraine days per month. Patients received CGRP monoclonal antibodies or antagonists, alongside sleep, dietary, and exercise interventions. Changes in migraine burden, neuropsychological outcomes, and adherence to lifestyle interventions were assessed over 12 months. Results: Migraine frequency significantly decreased from a median of 26.5 to 14 days per month (p < 0.001); PedMIDAS scores declined from 58.5 to 48.0 (p = 0.037); and acute analgesic use was reduced from 14 to 5 days per month (p < 0.001). Adherence to lifestyle interventions improved significantly (p < 0.001). No serious adverse events were reported, and minor side effects, such as injection site pain and dizziness, were self-limiting. Conclusions: CGRP-targeted therapies, combined with structured lifestyle modifications, safely and effectively reduce migraine burden in pediatric CM patients. These therapies have facilitated sustainable improvements in management and support their integration into comprehensive pediatric CM care. This study highlights the importance of integrating pharmacologic and lifestyle-based approaches for holistic pediatric migraine management. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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