Neuropsychiatric Diseases Research Articles

Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.

Purinergic receptors regulate the processing of neural information in the hippocampus and cerebral cortex, structures related to cognitive functions. These receptors are activated when astrocytic and neuronal populations release adenosine triphosphate (ATP) in an autocrine and paracrine manner, following sustained patterns of neuronal activity. The modulation by these receptors of GABAergic transmission has only recently been studied. Through their ramifications, astrocytes and GABAergic interneurons reach large groups of excitatory pyramidal neurons. Their inhibitory effect establishes different synchronization patterns that determine gamma frequency rhythms, which characterize neural activities related to cognitive processes. During early life, GABAergic-mediated synchronization of excitatory signals directs the experience-driven maturation of cognitive development, and dysfunctions concerning this process have been associated with neurological and neuropsychiatric diseases. Purinergic receptors timely modulate GABAergic control over ongoing neural activity and deeply affect neural processing in the hippocampal and neocortical circuitry. Stimulation of A2 receptors increases GABA release from presynaptic terminals, leading to a considerable reduction in neuronal firing of pyramidal neurons. A1 receptors inhibit GABAergic activity but only act in the early postnatal period when GABA produces excitatory signals. P2X and P2Y receptors expressed in pyramidal neurons reduce the inhibitory tone by blocking GABAA receptors. Finally, P2Y receptor activation elicits depolarization of GABAergic neurons and increases GABA release, thus favoring the emergence of gamma oscillations. The present review provides an overall picture of purinergic influence on GABAergic transmission and its consequences on neural processing, extending the discussion to receptor subtypes and their involvement in the onset of brain disorders, including epilepsy and Alzheimer's disease.

Toward Precise Modeling of Dopamine Release Kinetics: Comparison and Validation of Kinetic Models Using Voltammetry.

Dopamine (DA) is a neurotransmitter present within the animal brain that is responsible for a wide range of physiologic functions, including motivation, reward, and movement control. Changes or dysfunction in the dynamics of DA release are thought to play a pivotal role in regulating various physiological and behavioral processes, as well as leading to neuropsychiatric diseases. Therefore, it is of fundamental interest to neuroscientists to understand and accurately model the kinetics that govern dopaminergic neurotransmission. In the past several decades, many mathematical models have been proposed to attempt to capture the biologic parameters that govern dopaminergic kinetics, with each model seeking to improve upon a previous model. In this review, each of these models are derived, and the ability of each model to properly fit two fast-scan cyclic voltammetry (FSCV) data sets will be demonstrated and discussed. The dopamine oxidation current in both FSCV data sets exhibits hang-up and overshoot behaviors, which have traditionally been difficult for mathematical models to capture. We show that more recent models are better able to model DA release that exhibits these behaviors but that no single model is clearly the best. Rather, models should be selected based on their mathematical properties to best fit the FSCV data one is trying to model. Developing such differential equation models to describe the kinetics of DA release from the synapse confers significant applications both for advancing scientific understanding of DA neurotransmission and for advancing clinical ability to treat neuropsychiatric diseases.

Patterns, outcomes, and preventability of clinically manifest drug-drug interactions in older outpatients: a subgroup analysis from a 6-year-long observational study in North India.

Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion,every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.

The Effect of Maternal High-Fat or High-Carbohydrate Diet during Pregnancy and Lactation on Cytochrome P450 2D (CYP2D) in the Liver and Brain of Rat Offspring.

Cytochrome P450 2D (CYP2D) is important in psychopharmacology as it is engaged in the metabolism of drugs, neurosteroids and neurotransmitters. An unbalanced maternal diet during pregnancy and lactation can cause neurodevelopmental abnormalities and increases the offspring's predisposition to neuropsychiatric diseases. The aim of the present study was to evaluate the effect of maternal modified types of diet: a high-fat diet (HFD) and high-carbohydrate diet (HCD) during pregnancy and lactation on CYP2D in the liver and brain of male offspring at 28 (adolescent) or 63 postnatal days (young adult). The CYP2D activity and protein level were measured in the liver microsomes and the levels of mRNAs of CYP2D1, 2D2 and 2D4 were investigated both in the liver and brain. In the liver, both HFD and HCD increased the mRNA levels of all the three investigated CYP2D genes in adolescents, but an opposite effect was observed in young adults. The CYP2D protein level increased in adolescents but not in young adults. In contrast, young adults showed significantly decreased CYP2D activity. Similar effect of HFD on the CYP2D mRNAs was observed in the prefrontal cortex, while the effect of HCD was largely different than in the liver (the CYP2D2 expression was not affected, the CYP2D4 expression was decreased in young adults). In conclusion, modified maternal diets influence the expression of individual CYP2D1, CYP2D2 and CYP2D4 genes in the liver and brain of male offspring, which may affect the metabolism of CYP2D endogenous substrates and drugs and alter susceptibility to brain diseases and pharmacotherapy outcome.

Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (β [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons.

Stress and trauma are significant risk factors for many neuropsychiatric disorders and diseases, including anxiety disorders. Stress-induced anxiety symptoms have been attributed to enhanced excitability in circuits controlling fear, anxiety, and aversion. A growing body of evidence has implicated GABAergic neurons of the ventral tegmental area (VTA) in aversion processing and affective behavior. We used an unpredictable footshock (uFS) model, together with electrophysiological and behavioral approaches, to investigate the role of VTA GABA neurons in anxiety-related behavior in mice. One day after a single uFS session, C57BL/6J mice exhibited elevated anxiety-related behavior and VTA GABA neuron excitability. The enhanced excitability of VTA GABA neurons was correlated with increased glutamatergic input and a reduction in postsynaptic signaling mediated via GABAA and GABAB receptors. Chemogenetic activation of VTA GABA neurons was sufficient to increase anxiety-related behavior in stress-naïve mice. In addition, chemogenetic inhibition of VTA GABA neurons suppressed anxiety-related behavior in mice exposed to uFS. These data show that VTA GABA neurons are an early substrate for stress-induced anxiety-related behavior in mice and suggest that approaches mitigating enhanced excitability of VTA GABA neurons may hold promise for the treatment of anxiety provoked by stress and trauma.

Bioinformatics Analysis of 5HT2C Gene Cys23ser Polymorphism and Epigenetics Insights into the HTR2C Receptor Gene Regulation: Implications for Physiological Roles in the Brain

The expression profile, signaling and neuronal functions of the 5-HT2C receptor makes it a candidate of interest for the treatment of several neuropsychiatric diseases. The encoded ligand-gated G-protein coupled receptor (GPCR) protein responds to cell signaling through several neurotransmitters. Signal transduction through G-proteins is a prominent feature of several eukaryotes. In this review and analysis paper, we provide background literature on the unique biochemical, structural, and pharmacological properties of the 5-HT2c receptor and gene architecture, regulation, RNA editing and association studies of polymorphisms.Also on the evolutionary, and phylogenetic paths. of the 5HT2C gene. We conduct in silico predictions using bioinformatics tools SIFT and POLYPHEN to assess the effect of Cys23ser substitution in the N-terminal extracellular loop. Further, epigenetic analysis of the promoter and regions flanking the exon such as (DNase I Hypersensitivity, enhancer with TF binding site); methylation analysis of promoter (CpG methylation and CpG island); and histone marks with FAIRE. The results suggested that the cys23ser substitution can affect the 3D-protein structure. The additional cysteine amino acids (position-23,235,341) in human receptor could enable additional structural stability to the protein and may have evolved from previous ancestors (various mammals and primates) to aid the modulation of behavioral traits under evolutionary pressure. The alterations in DNA methylation and associated regulatory elements in promoter and upstream could impact gene expression, inactivation, genome stabilization, and inheritance which could have relevance in pathological states in the Central nervous system (CNS).

The Biomolecular Basis of Gut Microbiome on Neurological Diseases

The human gastrointestinal (GI) tract harbors many microorganisms, including viruses, protozoa, archaea, fungi, and bacteria. Altogether, these microbes constitute what we know as the gut microbiome (GM). These commensal communities have important implications for human health. They influence physiological processes through different mechanisms, including synthesizing neurotransmitters, regulating enzymatic pathways, and releasing molecules responsible for different signal pathways. The interaction between GM and brain function has been associated with the development and pathogenesis of neuropsychiatric diseases. This review discusses current studies targeting the regulation and modulation of GM in nerve, neuroendocrine, and immune pathways. Thus, we analyze current evidence on transcription, changes in composition, and specific interactions between the gut and brain from a biomolecular perspective. Special attention is paid to mood disorders and neurodegenerative diseases.

CLINICAL AND COGNITIVE PHENOTYPING OF COPY NUMBER VARIANTS PATHOGENIC FOR NEURODEVELOPMENTAL DISORDERS FROM A MULTI-ANCESTRY BIOBANK.

Rare copy number variants (CNVs) are pathogenic for neurodevelopmental disorders (NDDs) and effect neurocognitive impairment. In aggregate, NDD CNVs may present in up to 2% of population cohorts with implications for neuropsychiatric disease risk and cognitive health. However, analyses of NDD CNVs in biobanks or population cohorts have been hindered by limited clinical or cognitive phenotypes, and a lack of ancestral diversity. In the current proof-of-concept study, NDD CNV carriers were recontacted from BioMe, a multi-ancestry biobank derived from the Mount Sinai healthcare system, to enable 'deep phenotyping' beyond electronic health record outcomes. From BioMe biobank, 892 adult participants were recontacted, including 335 harboring NDD CNVs, 217 with schizophrenia and 340 neurotypical controls as comparators. Clinical and cognitive assessments were administered to each recruited participant. Seventy-three participants completed study assessments (mean age=48.8 years; 66% female; 36% African, 26% European, 34% Hispanic), or 8% of the recontacted subset, including 30 NDD CNV carriers across 15 loci. Among NDD CNV carriers, assessments indicated 40% with mood and anxiety disorders, 30% with learning disorders, and 13% with a history of special education. NDD CNV carriers were significantly cognitively impaired compared to controls on digit span backwards (Beta=-1.76, FDR=0.04) and digit span sequencing (Beta=-2.01, FDR=0.04). Feasibility of "recall-by-genotype" from a multi-ancestry biobank was established for NDD CNV carriers, along with comparator groups. The current study corroborated past reports of NDD CNVs effects of cognitive impairment, while elucidating clinical phenotypes for recalled individuals. Future "recall-by-genotype" studies may further facilitate clinical characterization of disease-relevant genomic variants.

Soft drug inhibitors for the epigenetic targets lysine-specific demethylase 1 and histone deacetylases.

Epigenetic modulators such as lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) are drug targets for cancer, neuropsychiatric disease, or inflammation, but inhibitors of these enzymes exhibit considerable side effects. For a potential local treatment with reduced systemic toxicity, we present here soft drug candidates as new LSD1 and HDAC inhibitors. A soft drug is a compound that is degraded in vivo to less active metabolites after having achieved its therapeutic function. This has been successfully applied for corticosteroids in the clinic, but soft drugs targeting epigenetic enzymes are scarce, with the HDAC inhibitor remetinostat being the only example. We have developed new methyl ester-containing inhibitors targeting LSD1 or HDACs and compared the biological activities of these to their respective carboxylic acid cleavage products. In vitro activity assays, cellular experiments, and a stability assay identified potent HDAC and LSD1 soft drug candidates that are superior to their corresponding carboxylic acids in cellular models.

Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives.

Lipids represent the most abundant molecular type in the brain with a fat content of approximately 60% of the dry brain weight in humans. Despite this fact, little attention has been paid to circumscribe the dynamic role of lipids in brain function and disease. Membrane lipids such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid and endocannabinoids finely regulate both synaptic receptors and ion channels that insure critical neural functions. After a brief introduction on brain lipids and their respective properties, we review here their role in regulating synaptic function and ion channel activity, action potential propagation, neuronal development, functional plasticity and their contribution in the development of neurological and neuropsychiatric diseases. We also provide possible directions for future research on lipid function in brain plasticity and diseases.

Whole exome sequencing analysis identifies genes for alcohol consumption

Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.

ELFN1 is a new extracellular matrix (ECM)-associated protein

AimsThe ELFN1, discovered in 2007, is a single-pass transmembrane protein. Studies conducted thus far to elucidate the function of the Elfn1 have been limited only to animal studies. These studies have reported that ELFN1 is a universal binding partner of metabotropic glutamate receptors (mGluRs) in the central nervous system and its functional deficiency has been associated with the pathogenesis of neurological and neuropsychiatric diseases. In 2021, we described the first disease-associated human ELFN1 pathogenic gene mutation. Severe joint laxity, which was the most striking finding of this new disease and was clearly seen in the patients since early infancy, showed that the ELFN1 may have a possible function in the connective tissue besides the nervous system. Here, we present the first experimental evidence of the extracellular matrix (ECM)-related function of the ELFN1. Materials and methodsPrimary skin fibroblasts were isolated from the skin biopsies of ELFN1 mutated patients and healthy foreskin donors. For the clinical trial in a dish, in vitro ECM and DEM (decellularized ECM) models were created from skin fibroblasts. All the in vitro models were comparatively characterized and analyzed. Key findingsThe mutation in the ELFN1 signal peptide region of patients resulted in a severe lack of ELFN1 expression and dramatically altered the characteristic morphology and behavior (growth, proliferation, and motility) of fibroblasts. SignificanceWe propose that ELFN1 is involved in the cell-ECM attachment, and its deficiency is critical enough to cause a loss of cell motility and soft ECM stiffness.

Maternal diseases and congenital anomalies of the kidney and urinary tract in offspring: a cohort study.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

Effects of psychedelic, DOI, on nucleus accumbens dopamine signaling to predictable rewards and cues in rats.

Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic 5-HT2A/2C agonist, DOI, effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients following acute DOI administration in rats during well learned Pavlovian tasks in which sequential cues predict rewards. We find that DOI (0.0-1.2 mg/kg, i.p.) increases dopamine signals, photometrically measured using GRABDA optical sensor, to rewards and proximal reward cues, but not to the distal cues that predict these events. We determine that the elevated dopamine produced by DOI to reward cues occurs independently of DOI-induced changes in reward value. The increased dopamine associated with predictable reward cues and rewards supports DOI-induced increases in prediction error signaling. These findings lay a foundation for developing psychedelic strategies aimed at engaging error-driven learning mechanisms to disrupt entrenched associations or produce new associations.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P<0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P<0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

The Effect of Neuropsychiatric Drugs on the Oxidation-Reduction Balance in Therapy.

The effectiveness of available neuropsychiatric drugs in the era of an increasing number of patients is not sufficient, and the complexity of neuropsychiatric disease entities that are difficult to diagnose and therapeutically is increasing. Also, discoveries about the pathophysiology of neuropsychiatric diseases are promising, including those initiating a new round of innovations in the role of oxidative stress in the etiology of neuropsychiatric diseases. Oxidative stress is highly related to mental disorders, in the treatment of which the most frequently used are first- and second-generation antipsychotics, mood stabilizers, and antidepressants. Literature reports on the effect of neuropsychiatric drugs on oxidative stress are divergent. They are starting with those proving their protective effect and ending with those confirming disturbances in the oxidation-reduction balance. The presented publication reviews the state of knowledge on the role of oxidative stress in the most frequently used therapies for neuropsychiatric diseases using first- and second-generation antipsychotic drugs, i.e., haloperidol, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole, mood stabilizers: lithium, carbamazepine, valproic acid, oxcarbazepine, and antidepressants: citalopram, sertraline, and venlafaxine, along with a brief pharmacological characteristic, preclinical and clinical studies effects.

Androgen effects on mesoprefrontal dopamine systems in the adult male brain

Epidemiological data show that males are more often and/or more severely affected by symptoms of prefrontal cortical dysfunction in schizophrenia, Parkinson’s disease and other disorders in which dopamine circuits associated with the prefrontal cortex are dysregulated. This review focuses on research showing that these dopamine circuits are powerfully regulated by androgens. It begins with a brief overview of the sex differences that distinguish prefrontal function in health and prefrontal dysfunction or decline in aging and/or neuropsychiatric disease. This review article then spotlights data from human subjects and animal models that specifically identify androgens as potent modulators of prefrontal cortical operations and of closely related, functionally critical measures of prefrontal dopamine level or tone. Candidate mechanisms by which androgens dynamically control mesoprefrontal dopamine systems and impact prefrontal states of hypo- and hyper-dopaminergia in aging and disease are then considered. This is followed by discussion of a working model that identifies a key locus for androgen modulation of mesoprefrontal dopamine systems as residing within the prefrontal cortex itself. The last sections of this review critically consider the ways in which the organization and regulation of mesoprefrontal dopamine circuits differ in the adult male and female brain, and highlights gaps where more research is needed.

Autoimmune Encephalitis: A Hidden Enigma Demystified.

Autoimmune encephalitis is a condition marked by inflammation in the brain due to an immune system response targeting self-antigens within the central nervous system (CNS). This class of disorders is at least as prevalent as infectious causes of encephalitis and encompasses a wide range of conditions. The field has rapidly expanded thanks to the identification of various pathogenic autoantibodies responsible for varied neurological and neuropsychiatric diseases. These disorders often present with distinct cognitive, seizure, and movement disorder phenotypes, making them clinically identifiable. Swift identification and treatment are pivotal for improving patient outcomes and promptly diagnosing associated tumors. This article zeroes in on autoantibody-mediated encephalitis syndromes involving neuronal cell-surface antigens. It sheds light on practical aspects of diagnosis and treatment, drawing from clinical experiences in managing such cases. Additionally, it underscores the ongoing importance of neuroimmunological advances that will shape the future diagnosis and treatment of these conditions.

Vitactions: vitamins for the brain

A novel concept has been recently put forward in the mind/body interface (https://doi.org/10.37349/ent.2024.00074). The new concept has led to a new word: vitaction. Vitactions offer benefits to the brain and mind comparable to the advantages vitamins provide for the body’s overall health. The field of vitactions is as it was the vitamin field one century ago, i.e., without tools to make a complete classification. I propose to classify vitactions into five categories according to the behaviours necessary to maintain balanced brain functionality. A deficit of vitactions would contribute to the enormous prevalence in developed countries of diseases ranging from type 2 diabetes to neuropsychiatric diseases. The concept should help to identify which vitactions are deficient and to outline how they can be progressively implemented to improve the quality of life. The parallelism vitactions/vitamins also extends to overdosing; both hypervitaminosis and hypervitactinosis may be detrimental. This perspective article argues that vitactions should be considered at the practical and the scientific research levels, and that a balanced vitamin and vitaction supply is essential for a better life. In addition, reasons for proposing a synonym, “vitactin”, are given.