Search Results (520)

Delirium is a complex neuropsychiatric syndrome with multifactorial pathophysiology, encompassing a wide range of neuropsychiatric symptoms, and its management remains a significant challenge in critical care. Although often managed with antipsychotics, like haloperidol, current research has predominantly focused on dopamine dysregulation as the primary driver of delirium, overlooking its broader neuroanatomical and neurochemical underpinnings. This has led to a majority of research focusing on haloperidol as a treatment for intensive care unit (ICU) delirium. Our review critically evaluates the role of haloperidol in ICU delirium management, particularly in light of recent large-scale randomized controlled trials (RCTs) that have primarily focused on delirium-free days and mortality as the primary endpoints. These studies highlight an limited understanding of the true nature of delirium treatment, which requires a broader, neuropsychiatric approach. We argue that future research should shift focus to neuropsychiatric symptoms such as agitation and psychosis and explore the clinical and functional benefits of reducing these distressing symptoms. Additionally, the stratification of delirium by subtypes and etiology, the enhancement of detection tools, and the adoption of multi-intervention and multi-disciplinary care approaches should be prioritized. Despite the methodological flaws in these studies, the findings support the safety of haloperidol in the ICU setting, with minimal risk of adverse events, particularly cardiac and neuropsychiatric. Moving forward, delirium research must integrate modern neuroscientific understanding and adopt more multi-disciplinary input and nuanced, patient-centered approaches to truly advance clinical care and outcomes. Full article

Background/Objectives: Multiple sclerosis (MS) is the most prevalent incurable nontraumatic neurological disability in young individuals. It causes numerous symptoms, including tingling, fatigue, muscle spasms, cognitive deficits, and neuropsychiatric disorders. This disease significantly worsens quality of life (QoL), and this dimension of general functioning provides valuable information about the effectiveness of treatment and well-being. There are psychological interventions that can improve QoL, but their number is limited. Therefore, searching for new methods that are as effective and safe as possible is ongoing. Methods: This review examines the potential effectiveness of transcranial direct current stimulation (tDCS) in improving the quality of life in patients with MS. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. Results: The search yielded seven studies in which QoL was a primary or secondary outcome. Stimulation protocols displayed heterogeneity, especially concerning the choice of the stimulation site. Four studies demonstrated the effectiveness of tDCS in improving QoL, all of which (two) used anodal stimulation of the left DLPFC. Stimulation of the motor cortex has produced mixed results. The potential mechanisms of action of tDCS in improving QoL in MS are explained. These include improved synaptic plasticity, increased cerebral blood flow, salience network engagement through tDCS, and reduction of beta-amyloid deposition. The limitations are also detailed, and recommendations for future research are made. Conclusions: While the evidence is limited, tDCS has shown potential to improve QoL in MS patients in some studies. Prefrontal stimulation appears promising, and further research is recommended to explore this approach. Full article

In this article, we focus on kynurenic acid metabolism in neuropsychiatric disorders and the biochemical processes involved in memory and cognitive impairment, followed by different approaches in the fight against dementia. Kynurenic acid—a biochemical part of L-tryptophan catabolism—is synthesized from L-kynurenine by kynurenine aminotransferases. Experimental pharmacological studies have shown that elevated levels of kynurenic acid in the brain are associated with impaired learning and that lowering kynurenic acid levels can improve these symptoms. The discovery of new compounds with the ability to block kynurenine aminotransferases opens new therapeutic avenues for the treatment of memory impairment and dementia. The newly developed Helix pomatia snail model of memory can be used for the assessment of novel pharmacological approaches. Dietary supplementation with natural molecular/herbal extracts, exercise, and physical activity have significant impacts on endogenous pharmacology by reducing kynurenic acid synthesis, and these factors are likely to significantly modulate steady-state biological conditions and delay the negative consequences of aging, including the onset of pathological processes. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and neuropsychiatric symptoms resulting from the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). Dopamine transporter scan (DATSCAN), based on single-photon emission computed tomography (SPECT), is commonly used to evaluate the loss of dopaminergic neurons in the striatum. This study aims to identify a biomarker from DATSCAN images and develop a machine learning (ML) algorithm for PD diagnosis. Using 13 DATSCAN-derived parameters and patient handedness from 1309 individuals in the Parkinson’s Progression Markers Initiative (PPMI) database, we trained an AdaBoost classifier, achieving an accuracy of 98.88% and an area under the receiver operating characteristic (ROC) curve of 99.81%. To ensure interpretability, we applied the local interpretable model-agnostic explainer (LIME), identifying contralateral putamen SBR as the most predictive feature for distinguishing PD from healthy controls. By focusing on a single biomarker, our approach simplifies PD diagnosis, integrates seamlessly into clinical workflows, and provides interpretable, actionable insights. Although DATSCAN has limitations in detecting early-stage PD, our study demonstrates the potential of ML to enhance diagnostic precision, contributing to improved clinical decision-making and patient outcomes. Full article

The substantial evidence supporting the ketogenic diet (KD) in epilepsy management has spurred research into its effects on other neurological and psychiatric conditions. Despite differences in characteristics, symptoms, and underlying mechanisms, these conditions share common pathways that the KD may influence. The KD reverses metabolic dysfunction. Moreover, it has been shown to support neuroprotection through mechanisms such as neuronal energy support, inflammation reduction, amelioration of oxidative stress, and reversing mitochondrial dysfunction. The adequate intake of dietary nutrients is essential for maintaining normal brain functions, and strong evidence supports the role of nutrition in the treatment and prevention of many psychiatric and neurological disorders. Obsessive–compulsive disorder (OCD) is a neuropsychiatric condition marked by persistent, distressing thoughts or impulses (obsessions) and repetitive behaviors performed in response to these obsessions (compulsions). Recent studies have increasingly examined the role of nutrition and metabolic disorders in OCD. This narrative review examines current evidence on the potential role of the KD in the treatment of OCD. We explore research on the KD’s effects on psychiatric disorders to assess its potential relevance for OCD treatment. Additionally, we identify key gaps in the preclinical and clinical research that warrant further study in applying the KD as a metabolic therapy for OCD. Full article

Efavirenz (EFV) causes neuropsychiatric effects such as anxiety, depression, and suicidal thoughts in people with HIV (PWH). Depressive disorders have been associated with the Tryptophan hydroxylase type 2 (TPH2) gene. Objectives: This study determines the genotypes and allelic frequencies of three TPH2 single nucleotide polymorphisms (SNPs) in a Mexican cohort of HIV-1 treatment-naïve-patients and the severity of depressive symptoms at baseline and after a four-week clinical follow-up of antiretroviral treatment. Methods: In a pilot prospective study, eighty-one antiretroviral treatment-naïve patients were recruited from the Infectious Disease Hospital, National Medical Center “La Raza”, in Mexico City. Of these, 39 were treated using a set-dose combination regimen of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus EFV and 42 were treated with TDF/FTC plus atazanavir/ritonavir (ATV/r), and fifty-nine control volunteers. Genomic DNA was obtained from peripheral blood mononuclear cells. All DNA samples underwent qPCR utilizing TaqMan probes for the three TPH2 SNPs studied. All participants underwent evaluation utilizing the Beck Depression Inventory. Results: Of the three SNPs examined, none exhibited any notable differences in the distribution of the alleles between the groups; nevertheless, rs4570625 TT and rs1386493 GG presented a twofold and fivefold greater risk of severe depression in PWH, respectively, independently of the treatment. Among PWH, those treated with EFV experienced severe depression at a higher rate of 90.4% after four weeks, compared to 87.5% in those treated with ATV/r. Conclusions: High rates of severe depression were identified in PWH, who presented the rs4570625 TT and rs1386493 GG polymorphic variants. Depression increased after four weeks of treatment and was higher with EFV than ATV/r. It is crucial to emphasize the necessity of conducting psychiatric monitoring for every patient with HIV and administering prompt antidepressant treatment. Full article

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal–midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS. Full article

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD). mTOR inhibitors, notably everolimus, have become central to TSC management, with documented efficacy in reducing the sizes of SEGAs and AMLs and showing promise in addressing additional TSC-related symptoms. Case Presentation: We report the case of an 11-year-old male diagnosed with TSC, presenting with hallmark features including hypopigmented macules, early-onset infantile spasms, SEGA, and AMLs. Initial interventions included adrenocorticotropic hormone (ACTH) therapy and sodium valproate for seizure management and a minimally invasive keyhole craniotomy for SEGA reduction. At age 12, oral everolimus therapy was introduced to address both SEGA recurrence risk and ASD-related social deficits. Over the course of 24 weeks, a reduction in the size and erythema of the patient’s FAs was observed, alongside improvements in social engagement, suggesting potential added benefits of systemic mTOR inhibition beyond tumor control. Results: Treatment with everolimus over a 24-month period led to significant reductions in both FA and AML size, as well as measurable improvements in ASD-associated behaviors. Therapeutic drug monitoring maintained serum levels within the effective range, minimizing adverse effects and underscoring the tolerability and feasibility of long-term everolimus administration. Conclusions: This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care. Full article

Background/Objectives: Olfactory dysfunction (OD) is associated with a variety of neurologic deficits and impacts socialization decisions, mood, and overall quality of life. As a common symptom comprising the long COVID condition, persistent COVID-19-associated olfactory dysfunction (C19OD) may further impact the presentations of neuropsychiatric sequelae. Our study aims to characterize the longitudinal burden of depression, anxiety, and neuropsychiatric symptoms in a population with C19OD. Methods: Individuals with perceived C19OD completed a psychophysical screening evaluation of their sense of smell using the comprehensive Sniffin’ Sticks olfactory assessment. Only those with validated psychophysical OD were included in this prospective longitudinal study for baseline and one-year follow-up. Participants also completed PHQ-9, Beck Anxiety Inventory (BAI), and neuropsychiatric symptom questionnaires at each time point. Anxiety, depression, and neuropsychiatric symptom prevalence was calculated and compared between time points with Pearson’s chi-squared, Fisher’s exact, and Wilcoxon rank sum tests. Results: Each neuropsychiatric symptom evaluated in this study was reported by 13–49% of longitudinal cohort participants at both baseline and follow-up, except for seizure (0% at baseline and follow-up) and word-finding difficulty (61–68% at baseline and follow-up). Word-finding and focus difficulties were the most commonly reported symptoms. In total, 41% of participants reported some level of depression at baseline and 38% of participants reported depression at one-year follow-up, while 29% and 27% of participants reported some level of anxiety at respective time points. Conclusions: Individuals with C19OD are at risk for developing persistent neuropsychiatric conditions. These neurologic and psychiatric sequelae are persistent with repeated longitudinal assessment, even at nearly 2.5 years following initial COVID-19 diagnosis. Full article

Background: Chronobiology has gained attention in the context of paediatric neurological and neuropsychiatric disorders, including migraine, epilepsy, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Disruptions in circadian rhythms are associated with key symptoms such as sleep disturbances, mood dysregulation, and cognitive impairments, suggesting a potential for chronobiology-based therapeutic approaches. Methods: This narrative review employs a systematic approach to identify relevant studies through searches of three major scientific databases, NCBI/PubMed, ScienceDirect, and Scopus, up to July 2024. We used a combination of broad and condition-specific keywords, such as “chronobiology”, “biorhythm”, “pediatric”, “epilepsy”, “ADHD”, and “ASD”, among others. Articles in English that focused on clinical features, treatments, or outcomes related to circadian rhythms in paediatric populations were included, while non-peer-reviewed articles and studies lacking original data were excluded. Rayyan software was used for article screening, removing duplicates, and facilitating consensus among independent reviewers. Results: A total of 87 studies were included in the analysis. Findings reveal a consistent pattern of circadian rhythm disruptions across the disorders examined. Specifically, dysregulation of melatonin and cortisol secretion is observed in children with ASD, ADHD, and PTSD, with altered circadian timing contributing to sleep disturbances and mood swings. Alterations in core clock genes (CLOCK, BMAL1, PER, and CRY) were also noted in children with epilepsy, which was linked to seizure frequency and timing. Chronotherapy approaches showed promise in managing these disruptions: melatonin supplementation improved sleep quality and reduced ADHD symptoms in some children, while light therapy proved effective in stabilizing sleep–wake cycles in ASD and ADHD patients. Additionally, behaviour-based interventions, such as the Early Start Denver Model, showed success in improving circadian alignment in children with ASD. Conclusions: This review highlights the significant role of circadian rhythm disruptions in paediatric neurological and neuropsychiatric disorders, with direct implications for treatment. Chronobiology-based interventions, such as melatonin therapy, light exposure, and individualized behavioural therapies, offer potential for improving symptomatology and overall functioning. The integration of chronotherapy into clinical practice could provide a paradigm shift from symptom management to more targeted, rhythm-based treatments. Future research should focus on understanding the molecular mechanisms behind circadian disruptions in these disorders and exploring personalized chronotherapeutic approaches tailored to individual circadian patterns. Full article

The fibronectin domain-containing protein 5 (FNDC5), or irisin, is an adipo-myokine hormone produced during exercise, which shows therapeutic potential for conditions like metabolic disorders, osteoporosis, sarcopenia, obesity, type 2 diabetes, and neurodegenerative diseases, including Alzheimer’s disease (AD). This review explores its potential across various pathophysiological processes that are often considered independent. Elevated in healthy states but reduced in diseases, irisin improves muscle–adipose communication, insulin sensitivity, and metabolic balance by enhancing mitochondrial function and reducing oxidative stress. It promotes osteogenesis and mitigates bone loss in osteoporosis and sarcopenia. Irisin exhibits anti-inflammatory effects by inhibiting NF-κB signaling and countering insulin resistance. In the brain, it reduces amyloid-β toxicity, inflammation, and oxidative stress, enhancing brain-derived neurotrophic factor (BDNF) signaling, which improves cognition and synaptic health in AD models. It also regulates dopamine pathways, potentially alleviating neuropsychiatric symptoms like depression and apathy. By linking physical activity to systemic health, irisin emphasizes its role in the muscle–bone–brain axis. Its multifaceted benefits highlight its potential as a therapeutic target for AD and related disorders, with applications in prevention, in treatment, and as a complement to exercise strategies. Full article

Background/Objectives: Individuals with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), an immune-modulated disorder, experience exacerbation-related neuropsychiatric symptoms, functional impairments, and high rates of developmental diagnosis. The literature describes links between giftedness and mental illness, and giftedness and autoimmune disorders. We sought to explore rates of giftedness among children with PANS as perceived by their caregivers, and to examine whether giftedness was related to PANS symptom severity, persistence, or duration. Methods: Data were extracted from a larger, 146-item survey, with 680 respondents meeting inclusion criteria of being a parent/guardian of a child with PANS and answering questions regarding perceived giftedness in empathy, social skills, verbal ability, reading, memory, math, creativity, or “other.” Results: In all, 604 respondents indicated some type of giftedness; the categories of giftedness were each endorsed by 30–57% of respondents. We found no significant associations between giftedness and severity of worst symptoms, persistence of symptoms, or length of time since symptom onset, once Bonferonni corrections were applied. Significantly more females than males were identified as gifted in creativity, but no other sex-related differences were seen. Thematic analysis of optional comments revealed three themes: (1) Elaboration on Types of Giftedness; (2) Objective Basis for Perceptions of Giftedness; and (3) Impact of PANS on Giftedness. Conclusions: The rate of giftedness reported by parents of PANS subjects in this study is much higher than would be expected in the general population, even when adjusting generously for potential overestimation. This study of the “flip side” of PANS should serve as impetus for future studies regarding giftedness in this population; a robust finding of exceptionally high rates of giftedness would have implications for diagnosis, interpretation of symptoms (for example, perfectionism and social challenges) and disease management. Full article

Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible. Full article

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS. Full article

Neuropsychiatric disorders are a public health concern, in which diagnosis and prognosis may be based on clinical symptoms that might often diverge across individuals. Schizophrenia is a major neuropsychiatric disorder, which may affect millions worldwide. However, the biochemical alterations of this disorder have not been comprehensively distinguished. In addition, there is less confidence in finding specific biomarkers for neuropsychiatric disorders, including schizophrenia, but rather a specific characteristic behavioral pattern. In general, maternal immune activation is considered to be one of the important factors in the development of neuropsychiatric disorders. Here, a mouse model of neuropsychiatric disorders was created, in which poly I:C, sodium dextran sulfate (DSS), and κ-carrageenan (CGN) were utilized for maternal immune activation during the pregnancies of mother mice. Subsequently, we examined the link between biochemical changes in p62 and/or glutamate aspartate transporter (GLAST) in the brains of offspring mice and the alteration in their experimental behavior scores. Furthermore, a therapeutic study was conducted on these neuropsychiatric disorder model mice using butyric acid, piceid, and metformin. It was found that some molecules could effectively improve the behavioral scores of neuropsychiatric model mice. Importantly, significant correlations between certain behavioral scores and p62 protein expression, as well as between the scores and GLAST expression, were recognized. This is the first report of a significant correlation between pathological behaviors and biochemical alterations in neuropsychiatric disorder model animals. This concept could contribute to the development of innovative treatments to at least ameliorate the symptoms of several psychiatric disorders. Full article