BACKGROUND: Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis.
METHODS: Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane\'s Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis.
RESULTS: For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson\'s disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015).
CONCLUSIONS: Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.

UNASSIGNED: Levetiracetam (LEV) is commonly prescribed for epilepsy management. However, neuropsychiatric disorders (NPDs) are concerning adverse effects that may result in medication discontinuation. This study aims to examine the incidence and factors influencing LEV associated NPDs in adult patients aged 50 years and above.
UNASSIGNED: A retrospective analysis was conducted on patients aged 50 years and above prescribed LEV between 2010 and 2020, with at least one follow-up appointment six months post-treatment initiation. The incidence of new-onset or aggravated NPDs and variables potentially influencing this risk were examined. Independent t-test, chi-squared, and Fisher\'s exact test were used, in addition to univariate and multivariate logistic regression.
UNASSIGNED: The study included 100 patients with a mean age at LEV start of 63.31 years (SD = 16.48). Neuropsychiatric symptoms were observed in 6 (6.0%) patients. Factors associated with new-onset NPDs were younger age at epilepsy diagnosis (p=0.005), younger age at LEV start (p=0.004), and concurrent use of Carbamazepine/Oxcarbazepine (p=0.004). On multivariate analysis, only the association with Carbamazepine/Oxcarbazepine remained significant (OR 14.62, 95% CI 1.86-114.70, p=0.011).
UNASSIGNED: The findings indicate that the incidence of NPDs in elderly patients is relatively low (6%). Further research with larger samples is needed in comparison with a younger sample as a control group to confirm these findings.

BACKGROUND: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T. gondii antibody positivity and neuropsychiatric disorders through a comprehensive prospective cohort study.
METHODS: The cohort study utilized the UK Biobank database to recruit 8814 individuals with no prior diagnosis of neuropsychiatric disorders. Cox proportional hazards models were employed to investigate the associations between T. gondii P22 antibody seropositivity (P22+) and the development of various types of neuropsychiatric disorders.
RESULTS: Of the population, 14.65 % tested positive for T. gondii P22 antibody. The presence of T. gondii P22 antibody showed a slight inverse association with epilepsy (HR: 0.28; 95 % CI: 0.10-0.77), while it was positively associated with an increased risk of developing anxiety disorders (HR: 1.38; 95 % CI: 1.04-1.83).
CONCLUSIONS: The study sample consisted mostly of white British individuals aged 40 to 69 years old. Although we adjusted for potential confounders, there may be other unmeasured and residual confounding factors that could have influenced our reported associations.
CONCLUSIONS: The findings suggested an increased risk of anxiety and potential evidence of epilepsy associated with T. gondii P22+. However, our analysis did not reveal an increased risk of several other neuropsychiatric conditions including Alzheimer\'s disease, dementia, substance abuse disorders, depression, and neurodegenerative disorders, associated with P22 antibody seropositivity.

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.

BACKGROUND: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies.
METHODS: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer\'s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses.
RESULTS: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00-2.02), ADHD (1.51, 1.15-1.98), schizophrenia (1.47, 1.15-1.87), and AD (1.57, 1.16-2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%.
CONCLUSIONS: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer\'s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

UNASSIGNED: Previous observational research has indicated a correlation between ferritin levels and neuropsychiatric disorders, although the causal relationship remains uncertain.
UNASSIGNED: The objective of this study was to investigate the potential causal link between plasma ferritin levels and neuropsychiatric disorders.
UNASSIGNED: A two-sample Mendelian randomization (MR) study was conducted, wherein genetic instruments associated with ferritin were obtained from a previously published genome-wide association study (GWAS). Summary statistics pertaining to neuropsychiatric disorders were derived from five distinct GWAS datasets. The primary MR analysis employed the inverse variance weighted (IVW) method and was corroborated by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were employed to identify potential pleiotropy and heterogeneity in the results.
UNASSIGNED: The fixed effects IVW method revealed a statistically significant causal relationship between plasma ferritin level and the occurrence of Alzheimer\'s disease (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.00-1.12, p = 0.037), as well as Parkinson\'s disease (OR = 1.06, 95% CI: 1.00-1.13, p = 0.041). Various sensitivity analyses were conducted, which demonstrated no substantial heterogeneity or pleiotropy. Conversely, no compelling evidence was found to support a causal association between ferritin and amyotrophic lateral sclerosis, schizophrenia, or major depressive disorder.
UNASSIGNED: This MR study provides evidence at the genetic level for a causal relationship between plasma ferritin and an increased risk of Alzheimer\'s disease and Parkinson\'s disease. The exact genetic mechanisms underlying this connection necessitate further investigation.

UNASSIGNED: Observational studies have reported associations between gut microbiota composition and central nervous system diseases. However, the potential causal relationships and underlying mechanisms remain unclear. Here, we applied Mendelian randomization (MR) to investigate the causal effects of gut microbiota on cortical surface area (SA) and thickness (TH) in the brain.
UNASSIGNED: We used genome-wide association study summary statistics of gut microbiota abundance in 18,340 individuals from the MiBioGen Consortium to identify genetic instruments for 196 gut microbial taxa. We then analyzed data from 56,761 individuals from the ENIGMA Consortium to examine associations of genetically predicted gut microbiota with alterations in cortical SA and TH globally and across 34 functional brain regions. Inverse-variance weighted analysis was used as the primary MR method, with MR Egger regression, MR-PRESSO, Cochran\'s Q test, and leave-one-out analysis to assess heterogeneity and pleiotropy.
UNASSIGNED: At the functional region level, genetically predicted higher abundance of class Mollicutes was associated with greater SA of the medial orbitofrontal cortex (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002), as was higher abundance of phylum Tenericutes (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002). Additionally, higher abundance of phylum Tenericutes was associated with greater SA of the lateral orbitofrontal cortex (β = 10.51 mm2, 95% CI: 3.24-17.79 mm2, p = 0.0046). No evidence of heterogeneity or pleiotropy was detected.
UNASSIGNED: Specific gut microbiota may causally influence cortical structure in brain regions involved in neuropsychiatric disorders. The findings provide evidence for a gut-brain axis influencing cortical development, particularly in the orbitofrontal cortex during adolescence.

BACKGROUND: Recent studies show that neuropsychiatric disorders are the most frequent sequelae of COVID-19 in children.
OBJECTIVE: Our work aimed to evaluate the impact of SARS-CoV-2 infection on behavior and sleep in children and adolescents.
METHODS: We enrolled 107 patients aged 1.5-18 years who contracted COVID-19 between one year and one month prior to data collection, referred to the University of Campania Luigi Vanvitelli in Italy. We asked their parents to complete two standardized questionnaires for the assessment of behavior (Child Behavior CheckList (CBCL)) and sleep (Sleep Disturbance Scale for Children (SLDS)). We analysed and compared the results with a control group (pre-COVID-19 pandemic).
RESULTS: In the COVID-19 group, the major results were found for sleep breathing disorders, sleep-wake transition disorders and disorders of initiating and maintaining sleep for the SDSC questionnaire, and internalizing scale, total scale and anxiety/depression for the CBCL questionnaire. The comparison of the CBCL results of the cases with the controls revealed statistically significant differences for the following items: internalizing scale, externalizing scale, somatic complaints, total score, thought problems [(p < 0.01)], anxious/depressed problems and withdrawn [(p < 0.001)].
CONCLUSIONS: COVID-19 has impacted children\'s and adolescents\' mental health. Adolescents were the most affected patient group for internalizing problems, including anxiety and depression.

Nerve Growth Factor (NGF) and Brain derived Neurotrophic Factor (BDNF) mature/precursor imbalance in tears and serum is suggested as a risk factor and symptomatology aggravation in ophthalmology and neuropsychiatric disturbances. Cognitive and mood alterations are reported by patients with Graves\' Orbitopathy (GO), indicating neurotrophin alterations might be involved. To address this question, the expression levels of NGF and BDNF and their precursors in serum and tears of GO patients were analyzed and correlated with the ophthalmological and psycho-cognitive symptoms. Hamilton Rating Scale for Anxiety (HAM-A) and Depression (HAM-D), Temperament and Character Inventory (TCI), and Cambridge Neuropsychological Test Automated Battery (CANTAB) test were used as a score. NGF and BDNF levels were measured using ELISA and Western Blot and statistically analyzed for psychiatric/ocular variable trend association. GO patients show memorization time and level of distraction increase, together with high irritability and impulsiveness. HAM-A and CANTAB variables association, and some TCI dimensions are also found. NGF and BDNF expression correlates with ophthalmological symptoms only in tears, while mature/precursor NGF and BDNF correlate with the specific psycho-cognitive variables both in tears and serum. Our study is the first to show that changes in NGF and BDNF processing in tears and serum might profile ocular and cognitive alterations in patients.