Neurological and Neurobehavioral Disorders Associated with Toxoplasma gondii Infection in Humans

The intracellular parasite Toxoplasma gondii is estimated to infect up to 30% of the world population, leading to lifelong chronic infection of the brain and muscle tissue. Although most latent T. gondii infections in humans have traditionally been considered asymptomatic, studies in rodents suggest phenotypic neurological changes are possible. Consequently, several studies have examined the link between T. gondii infection and diseases such as schizophrenia, epilepsy, depression, bipolar disorder, dysphoria, Alzheimer’s disease, Parkinson’s disease, and obsessive-compulsive disorder (OCD). To date, there is varying evidence of the relationship of T. gondii to these human neurological or neurobehavioral disorders. A thorough review of T. gondii literature was conducted to highlight and summarize current findings. We found that schizophrenia was most frequently linked to T. gondii infection, while sleep disruption showed no linkage to T. gondii infection, and other conditions having mixed support for a link to T. gondii. However, infection as a cause of human neurobehavioral disease has yet to be firmly established.

RORγt-Expressing Pathogenic CD4+T Cells Cause Brain Inflammation During Chronic Colitis

Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease (IBD) patients remains unknown. Studies have linked the Th17 subset of CD4+T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis (MS), ischemic brain injury, and Alzheimer's disease. To better understand how CD4+T lymphocytes, contribute to brain pathology in chronic intestinal inflammation, we investigated the development of brain inflammation in the T cell transfer model of chronic colitis. Our findings demonstrate that CD4+T cells infiltrate the brain of colitic Rag1-/- mice in proportional levels to colitis severity. Colitic mice developed hypothalamic astrogliosis that correlated with neurobehavioral disorders. Moreover, the brain-infiltrating CD4+T cells expressed Th17 cell transcription factor RORγt and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of RORγt-deficient naive CD4+T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1-/- recipients, with significantly less brain infiltration of CD4+T cells. These findings suggest that pathogenic RORγt+CD4+T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation.

Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

The Global Misdiagnosis of ADHD and the Devastating Long-Term Effects

One of the most globally prevalent neurobehavioral disorders, attention-deficit hyperactivity disorder (ADHD), affects approximately 6.1 million children in the United States alone (CDC, 2020). It was found that childhood ADHD cases from 2003-2011 increased by 42 percent, resulting in questions about the validity of diagnosed cases (NIH, 2017). Furthermore, when compared to other countries, the United States shows an alarmingly high prevalence of ADHD cases in children.

Cesarean Delivery on Maternal Request and Common Child Health Outcomes: A Prospective Cohort Study

Cesarean delivery (CD) versus vaginal delivery was reported to increase the risks of childhood obesity, pneumonia, anemia, and neurobehavioral disorders, but few studies were able to deal with the confounding biases associated with medical conditions indicating cesareans. This prospective cohort study aims to investigate the associations of non-medically indicated CD on maternal request (CDMR) with multiple child health outcomes. Among live-born infants whose mothers participated in a randomized controlled trial on micronutrient supplementation and pregnancy outcomes during 2006-2009 in 5 rural counties in Hebei Province, China, 6972 singletons born by full-term spontaneous vaginal delivery (SVD) and 3626 by CDMR were selected and followed up at 1.5-5 years in 2011. The primary outcome was obesity, defined as a weight-for-height z-score >3. The secondary outcomes included self-reported pneumonia, anemia defined as hemoglobin <110 g/L, and neurobehavioral disorders identified by Child Behavior Checklist and Bayley Scales of Infant Development. Compared with SVD, CDMR was associated with increased risks of obesity (adjusted odds ratio [aOR] 1.41; 95% confidence interval [CI] 1.14-1.75) and anemia (aOR 1.65; 95% CI 1.28-2.12), but not with the risk of pneumonia (aOR 1.16; 95% CI 0.94-1.45) or neurobehavioral disorders (aORs varied from 0.82 to 1.13) in childhood. Conclusion: CD, independent of cesarean indications, is likely associated with childhood obesity and anemia, indicating a need to keep pregnant women informed, especially those seeking CDMR, a need to explore possible improvement on obstetric service, and even a need for main stakeholders to reach a compromise in making a cesarean decision.

Neuropsychiatric Aspects in a Patient Diagnosed with Frontotemporal Dementia: Clinical Case of Low Incidence and Prevalence Disease in Colombia

Frontotemporal dementia (FTD) is a neuropsychiatric pathology characterized by dysfunctions in the frontal lobe of the brain, especially in planning, execution, and inhibition tasks, with an inability to make decisions and handle different sequences, also affecting the temporal lobe. The patient presents alterations to store, consolidate, and recall information. These neurocognitive deficits are accompanied by neurobehavioral disorders such as depression, anxiety, and apathy that contribute to the worsening of the quality of life, with a high impact on the individual, social, and family level. To identify the neurobehavioral disorders and neurocognitive deterioration that present a patient diagnosed with FTD: clinical case of low incidence and prevalence disease in Colombia. A 40-year-old man, with progressive deterioration of his immediate verbal memory, low verbal fluency, aberrant motor behavior, sexual impulsivity, alterations in his executive functions, especially in planning tasks, decision-making, and inhibition was found to have a lesser degree of affectation in his visuospatial functioning and visuoconstructive abilities. It was found that the patient presents a severe dysexecutive syndrome associated with a clinical picture of FTD, correlated with an inability to process and recall information, accompanied by disorders such as depression, anxiety, and apathy. It is necessary to generate a functional neurorehabilitation plan that aims to improve the quality of life in these patients. In the same way, it is necessary to create new lines of research and intervention that have the purpose to create a greater field of heuristics or new questions in this type of neurodegenerative pathologies.

Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse

Altered structure, expression, and regulation of the presynaptic serotonin (5-HT) transporter (SERT) have been associated with multiple neurobehavioral disorders, including mood disorders, obsessive-compulsive disorder (OCD), and autism spectrum disorder (ASD). Opportunities to investigate mechanistic links supporting these associations were spurred with the identification of multiple, rare human SERT coding variants in a study that established a male-specific linkage of ASD to a linkage marker on chromosome 17 which encompassed the location of the SERT gene (SLC6A4). We have explored the most common of these variants, SERT Ala56, in vitro and in vivo. Results support a tonic elevation of 5-HT transport activity in transfected cells and human lymphoblasts by the variant in vitro that leads to an increased 5-HT clearance rate in vivo when studied in the SERT Ala56 mouse model, along with altered sensitivity to SERT regulatory signaling pathways. Importantly, hyperserotonemia, or an elevated whole blood 5-HT, level, was found in SERT Ala56 mice, reproducing a well-replicated trait observed in a significant fraction of ASD subjects. Additionally, we found multiple biochemical, physiological, and behavioral alterations in the SERT Ala56 mice that can be analogized to those observed in ASD and its medical comorbidities. The similarity of the functional impact of the SERT Ala56 variant to the consequences of p38α MAPK activation, ascribed to the induction of a biased conformation of the transporter toward an outward-facing conformation, has resulted in successful efforts to restore normal behavioral and bowel function via pharmacological and genetic p38α MAPK targeting. Moreover, the ability of the inflammatory cytokine IL-1β to enhance SERT activity via a p38α MAPK-dependent pathway suggests that the SERT Ala56 conformation mimics that of a chronic inflammatory state, supporting findings in ASD of elevated inflammatory cytokine levels. In this report, we review studies of the SERT Ala56 variant, discussing opportunities for continued insight into how chronically altered synaptic 5-HT homeostasis can drive reversible, functional perturbations in 5-HT sensitive pathways in the brain and periphery, and how targeting the SERT regulome, particularly through activating pathways such as those involving IL-1β/p38α MAPK, may be of benefit for neurobehavioral disorders, including ASD.

“Clinical Study of Memory Disorders in Aging Patients with Associated Cardiovascular, Neurological, Neurobehavioral and Metabolic Diseases”. A Review

We have observed semantic memory and episodic memory disorders (100%) in patients ranging from 40 to 92 years-old, associated to cardiovascular diseases and blood hypertension (82%), sleep disorders (50%), neurobehavioral disorders (44%), such as depression, anxiety, aggression, and vascular demencia, disorders of language (36%), neurosensory disorders (28%), as diminution of visual and hearing acuity, dizziness (26%), Parkinson disease (34%), Alzheimer disease (21%), gait disturbances (10%), vertigo (10%), cervicalgia and cervicogenic headache (10%) trigeminal neuralgia (2%,), We observed as comorbidities the following non-nervous diseases: metabolic diseases as diabetes (21%) and hypothyroidism (5%), gastrointestinal pathology (21%), such as constipation, loss of sphincter control, and gastritis, arthritis (13%), prostatic hypertrophy (1%) and loss of weight (1%). We consider that according to their high frequency the most risk factors associated to memory disorders are cardiovascular diseases and blood hypertension (82%), sleep disorders (50%), neurobehavioral disorders (44%), such as depression, anxiety, aggression, and vascular demencia, disorders of language (36%), neurosensory disorders (28%), as diminution of visual and hearing acuity, dizziness (26%), and Parkinson disease (34%).