This systematic review explores the role of the endocannabinoid system (ECS) in prodromal psychosis and its potential as a therapeutic target. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 22 studies published between 2000 and 2025 were analyzed, comprising preclinical research, genetic studies, neuroimaging investigations, and clinical trials. Converging evidence suggests that ECS alterations precede and potentially contribute to the development of psychotic symptoms, with CB1 receptor modifications and endocannabinoid levels correlating with symptom severity and transition risk to full-blown psychosis. Neuroimaging studies revealed reduced CB1 receptor availability in key brain regions in high-risk subjects, and intervention studies, particularly with cannabidiol-though its therapeutic mechanisms likely extend beyond ECS modulation to include dopaminergic and other neurotransmitter pathways-have shown promising results. Proposed mechanisms of action include stress response attenuation, neuroinflammatory modulation, neurodevelopmental stabilization, and normalization of the dopamine-glutamate interface. Despite limitations of existing studies, primarily small size and short duration, this review provides a solid foundation for developing ECS-targeted interventions as a promising approach to modify disease trajectory during the prodromal phase, potentially offering safer and more effective therapeutic options for individuals at clinical high risk for psychosis.

This study aims to investigate the antidepressant properties of Hispidulin, a flavonoid present in Scutellaria barbata D. Don. The selection of Hispidulin stems from its notable inhibitory activity against Xanthine Oxidase (XO), a parameter in the pathophysiology of depression. Mice were subjected to a rigorous evaluation using a murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression for 21 days and antidepressant properties were rigorously assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Imipramine and fluoxetine were used as standard drugs. Additionally, neurochemical analyses were conducted to quantify serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels in the cortex, hippocampus, and hypothalamus. Further mechanistic insights were sought through the estimation of monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in the brain. Plasma nitrite and corticosterone levels were also measured to delineate the underlying mechanism of action. Hispidulin demonstrated significant antidepressant effects, as evidenced by reduced immobility time in TST and FST and increased exploratory behavior in OFT. Neurochemical analysis revealed restoration of 5-HT, NE, and DA levels in key brain regions. Furthermore, Hispidulin modulated MAO activity and enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were elevated, indicating enhanced nitric oxide synthesis, while corticosterone levels were reduced. Our findings indicate that Hispidulin exerts potent antidepressant effects, potentially mediated through its influence on monoaminergic neurotransmitters, MAO activity, and antioxidant defenses. These results provide valuable mechanistic insights into the antidepressant action of Hispidulin, supporting its potential therapeutic application in depressive disorders.

From bladder to brain: How you know when it's time to go.

Combined chronic oral methylphenidate and fluoxetine treatment increases CB1 receptor density in the somatosensory forelimb region.

Harnessing exercise for brain health: BDNF, neuroplasticity & well-being.

Traumatic brain injury (TBI) is a significant public health concern and its rising prevalence in road traffic accidents underscores the need for deeper understanding and tailored investigation. This study explores the feasibility of employing the female finite element head model (FeFEHM) to analyse biomechanical responses in two distinct road traffic accident scenarios, focusing on strain and stress distribution in critical brain structures. Two collision scenarios from the German In-Depth Accident Study (GIDAS) were reconstructed using validated Total Human Model for Safety (THUMS) simulations. The extracted skull kinematics were applied to the FeFEHM in ABAQUS to compute maximum principal strain, von Mises stress, and intracranial pressure across key brain regions, including the corpus callosum and pituitary gland. Simulations revealed strain concentrations in the parietal and temporal lobes, while the mid-body region was the most affected in the corpus callosum. Pituitary gland deformation was minimal under both loading conditions. Our findings align qualitatively with reported injury sites and injury risk was consistent with those observed in the real-world crashes. The findings highlight the potential of integrating sex-specific biomechanical models into crash biomechanics workflows. Future work should extend this approach across larger datasets and impact scenarios to support its implementation in regulatory and engineering contexts, since the actual sample size prevents conclusions regarding sex-specific biomechanics.

Brain histaminergic system: An emerging target for the treatment of feeding and eating-related disorders.

Intracortical functional connectivity during deep sleep reveals prosocial preferences.

Functional characteristics of speech perception decline in healthy aging based on resting-state EEG-fNIRS.

Increased sympathetic outflow induced by ventromedial hypothalamic nucleus activation aggravates cardiac electrophysiology disturbance after myocardial ischemia-reperfusion injury.

An optimized framework for Parkinson's disease classification using multimodal neuroimaging data with ensemble-based and data fusion networks.

Role of amylin in feeding and satiation.

Depression, which is increasingly prevalent among older adults, has traditionally been diagnosed through symptom-based questionnaires. However, emerging evidence suggests that retinal changes could serve as objective biomarkers for depression. In this study, we investigated the optic disc signature of depression by leveraging automated fundus morphometrics (deep learning segmentation) and Olink-based plasma proteome profiling to explore potential mechanistic pathways. A total of 412 participants from two independent cohorts, the UK Biobank and the Guangdong Ophthalmic-Psychological Health Study (GD-OPHS), were included in the analysis. Our findings indicate that individuals with depression exhibited increased roundness of the optic disc (UK Biobank: OR = 1.12, 95% CI = 1.01–1.25; GD-OPHS: OR = 1.16, 95% CI = 1.02–1.32) and a larger optic disc tilt angle (UK Biobank: OR = 2.83, 95% CI = 1.61–4.96; GD-OPHS: OR = 1.81, 95% CI = 1.02–3.21). Importantly, optic disc roundness correlated with the expression of two depression-related proteins, LRRN1 (p = 0.010) and PRL (p = 0.022). Both LRRN1 and PRL are enriched in the retina, as well as in key brain regions involved in emotional regulation, including the cerebral cortex, thalamus, and hippocampus. Given the strong connections between the retina and the central nervous system, our results suggest that optic disc morphology may serve as an objective, non-invasive biomarker for depression.

BackgroundBlepharospasm, characterized by involuntary contractions of the orbicularis oculi muscles, significantly impairs the quality of life. Its pathophysiology remains unclear. Inter-hemispheric cooperation is a prominent feature of the human brain. This study utilizes resting-state functional magnetic resonance imaging (rs-fMRI) to explore inter-hemispheric functional cooperation in blepharospasm patients by examining connectivity between functionally homotopic voxels (CFH), aiming to identify neural disruptions associated with the disorder.MethodsWe recruited 30 patients with blepharospasm and 30 age-, sex-, and education-matched healthy controls. All participants underwent rs-fMRI scanning. CFH maps were generated for each participant to quantify inter-hemispheric connectivity at the voxel level. Group differences were assessed, and partial correlation analyses were performed in the patient group to examine the relationship between aberrant CFH values and clinical variables.ResultsCompared to healthy controls, patients with blepharospasm showed significantly increased CFH in the left putamen and left precentral gyrus. However, these aberrant CFH values did not significantly correlate with clinical variables, including disease duration or total Jankovic Rating Scale (JRS) scores and its subscales.ConclusionsThis study identifies increased inter-hemispheric functional connectivity (FC) within key motor-related brain regions in blepharospasm. The observed hyperconnectivity in the putamen and precentral gyrus may reflect a compensatory neural mechanism to counteract motor dysfunction. These findings provide novel insights into the pathophysiology of blepharospasm and suggest that modulating inter-hemispheric communication may be a potential therapeutic target.

Low birth weight and preterm infants may have higher risks of poor health. As the key brain region for learning and memory, normal development of the hippocampus is crucial for the cognitive abilities of preterm infants. This study aimed to analyze hippocampal glutamate (Glu) levels and morphometric changes in preterm infants at term-equivalent age (TEA) with different birth weights. Eighty-seven infants (23 full-term infants and 64 preterm infants) born between 2023 and 2025, underwent magnetic resonance imaging (MRI) at TEA. Glutamate chemical exchange saturation transfer (GluCEST) MRI and 3D-SPACE were used to assess hippocampal Glu levels and morphometric changes. The preterm cohort was categorized by birth weight: preterm infants born at extremely and very low birth weight (Group 1), preterm infants born at low birth weight (Group 2) and preterm infants born at normal birth weight (Group 3). Full-term infants born at normal birth weight (Group 4) were included as controls. Group 1 exhibited elevated Glu levels, Group 2 showed intermediate Glu levels. In infants with normal birth weight, preterm at TEA have higher glutamate levels than full-term infants. No differences were observed in the bilateral hippocampal Glu levels within each group. The bilateral hippocampal volume, surface area, and long diameter in Group 1 were all significantly smaller than those in Group 3. Morphological analysis revealed rightward hippocampal asymmetry in all preterm groups. Birth weight significantly influences hippocampal glutamate levels and morphology in preterm infants. These findings offer new insights into the metabolic variations in preterm neurodevelopment.

BackgroundFetal Growth Restriction (FGR) is a complex neurodevelopmental condition marked by the failure of a fetus to reach its genetically determined growth potential, leading to significant neurodevelopmental risks. Emerging MR scans exhibit superiority to traditional US-based diagnostic approaches, while quantitative morphological analysis of FGR is still lacking.MethodsThis study explores the effects of FGR on fetal brain development using advanced Magnetic Resonance Imaging (MRI) techniques. A comprehensive analysis of 35 brain regions was conducted, focusing on detailed cortical properties such as curvature, sulcal depth, surface area, cortical gray matter volume, and cortical thickness, while distinguishing between the left and right hemispheres. Our comprehensive analysis leverages super-resolution reconstruction, segmentation, and surface reconstruction algorithms to obtain statistical data.ResultsOur analysis revealed that (1) FGR equally affected both brain hemispheres; (2) In the absence of differentiation between brain regions, different cortical metrics had no significant effect on FGR; and (3) the most significant cortical metrics were primarily observed in cortical thickness and sulcal depth; (4) a regression model based on only seven key brain regions could effectively predict FGR. The findings demonstrate the value of high-resolution MRI in detecting early biomarkers for FGR, paving the way for improved prenatal care and targeted therapeutic strategies.ConclusionsThe findings highlight the importance of high-resolution MRI in identifying early biomarkers for FGR. The study emphasizes the value of advanced cortical analysis in understanding the pathophysiological mechanisms underlying FGR and offers a robust framework for early diagnosis and intervention. These insights could contribute to improved prenatal care and targeted therapeutic strategies, ultimately enhancing outcomes for affected populations.

Mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer’s disease (AD), comprises three potential trajectories: reversion, stability, or progression. Accurate prediction of these trajectories is crucial for disease modeling and early intervention. We propose a novel analytical framework that integrates a healthy control–AD difference template (HAD) with a large-scale Granger causality algorithm based on long short-term memory networks (LSTM-lsGC) to construct effective connectivity (EC) networks. By applying principal component analysis for dimensionality reduction, modeling dynamic sequences with LSTM, and estimating EC matrices through Granger causality, the framework captures both symmetrical and asymmetrical connectivity, providing a refined characterization of the network alterations underlying MCI progression and reversion. Leveraging graph-theoretical features, our method achieved an MCI subtype classification accuracy of 84.92% (AUC = 0.84) across three subgroups and 90.86% when distinguishing rMCI from pMCI. Moreover, key brain regions, including the precentral gyrus, hippocampus, and cerebellum, were identified as being associated with MCI progression. Overall, by developing a symmetry-aware effective connectivity framework that simultaneously investigates both MCI progression and reversion, this study bridges a critical gap and offers a promising tool for early detection and dynamic disease characterization.

Anorexia nervosa (AN) is a complex psychiatric disorder characterized by severe caloric restriction and distorted body image, leading to significant psychological and physiological complications. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognitive function and metabolic regulation. A mutation in the BDNF gene is associated with anorexia nervosa. This study examines the effects of food restriction, refeeding and short-term refeeding on the expression of Bdnf and its receptor (tropomyosin receptor kinase B TrkB/Ntrk2) in key brain regions involved in reward and cognitive function. We assessed BDNF mRNA levels in the dorsal striatum (DS), nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC) of AN-like mice subjected to different feeding regimes combined with or without physical activity. Cognitive flexibility was assessed using the Y-maze test. Whole RNA sequencing was also performed to analyse gene expression changes. Food restriction induced a transient decrease in cognitive flexibility and significantly decreased Bdnf expression in the DS and PFC. Progressive refeeding restored Bdnf in the DS but not the PFC. Short refeeding restored Bdnf levels to baseline. TrkB expression is increased by restriction only in the PFC. The presence of a running wheel cancelled these effects, suggesting an interaction between physical activity and diet. Pathway analysis of dysregulated genes revealed enrichment in immune regulation and cell-cell communication pathways. These findings highlight the complex relationship between diet, exercise, and brain function in AN-like mouse model and suggest avenues for further research into the clinical relevance of BDNF and TrkB as biomarkers of eating disorders.

Foetal alcohol spectrum disorders (FASDs) refer to a range of adverse physical, behavioural and cognitive effects caused by perinatal alcohol exposure. While cognitive impairments are well documented, FASD has also been associated with sleep disturbances and circadian rhythm disruptions. This study aimed to examine the effects of perinatal alcohol exposure on circadian rhythms at behavioural and gene expression levels across two developmental stages (adolescence and adulthood) in both male and female mice. Using a validated prenatal and lactation alcohol exposure (PLAE) protocol, we assessed circadian patterns of locomotor activity under free-running conditions and spatial memory performance during adolescence and adulthood. Additionally, we evaluated the impact of PLAE on circadian expression of clock and non-circadian genes involved in neurotransmission across key brain regions, including the medial prefrontal cortex and hippocampus. PLAE altered circadian rhythmicity and impaired spatial memory. Gene expression analyses revealed disrupted oscillatory patterns in clock genes and in genes related to plasticity and cognition, including those from the expanded endocannabinoid system (e.g. Cnr1, Dagla, Faah) and other neurotransmitter systems (e.g. Oprm1, Slc17a8, Drd1, Gabra1). These findings underscore the impact of early alcohol exposure on biological rhythms and neurobehavioural function, highlighting circadian dysregulation as a contributing factor to FASD.

BackgroundDepression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.MethodsTo investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.ResultsVoxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.ConclusionsOur results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.