Psychiatric Disorders Associated With Infancy, Childhood, and Adolescence

This chapter covers key psychiatric disorders of infancy, childhood, and adolescence. In some instances, the disorders are mentioned briefly herein and covered in more detail in other chapters, as indicated. Attention-deficit/hyperactivity disorder (ADHD) is a neurobiologic disorder present in 11% of US children between the ages of 4 and 17 years and is 3 times more common in boys than in girls. Some symptoms must be present before age 12 years, although the average age at diagnosis is 7 years. The causes of ADHD are unknown. However, several factors have been suggested that likely mediate expression of ADHD, including prematurity, prenatal toxin exposure, mechanical insults to the nervous system, and natal stress.

P.037 Benefits of Treatment with OnabotulinumtoxinA in Naive and Non-naive Patients with Cervical Dystonia are Sustained over Time in CD PROBE

Background: The sustained effects of onabotulinumtoxinA in patients with cervical dystonia (CD) who were naïve or non-naïve to botulinum toxin at enrollment in CD PROBE (CD Patient Registry for Observation of BOTOX® Efficacy) were evaluated. Methods: Patients were included if they completed all three treatment cycles and had accompanying data in this prospective, observational study. Assessments included CD severity, Cervical Dystonia Impact Profile (CDIP-58), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), treatment interval, total dose, and adverse events (AEs). Results: Changes in severity following each onabotulinumtoxinA treatment were generally similar between naïve (n=212) and non-naïve (n=138) patients. Severity scores were maintained or improved in most patients with mild/moderate symptoms, while 30.0-66.7% with the highest severity scores shifted to a lower score across treatments. Sustained improvements were seen in all CDIP-58 subscales and TWSTRS total scores irrespective of baseline CD severity and toxin status. The median time interval between injections was similar in naïve (93.0–98.0 days) and non-naïve patients (96.0–97.0 days); doses tended to be lower in naïve patients. The most common AEs (dysphagia, muscular weakness) were similar. Conclusions: CD severity was attenuated by repeat onabotulinumtoxinA treatments at consistent intervals regardless of prior botulinum toxin exposure. Treatments were well tolerated.

Environmental toxic factors and clinical pattern of Parkinson’s disease

Background: Parkinson’s disease (PD) – the most common neuro-degenerative movement disorder – is considered a result of a multifactorial pathogenic process modulated by cumulative and interactive effects of genes and exposures. An environmental exposure could enhance or create dopaminergic neurons vulnerability and increase PD risk. The purpose of the study was to find if excessive exposure to toxic environmental factors may influence clinical pattern of PD. Material and methods: The study was conducted on 111 patients diagnosed with PD, study group being defined as PD exposed to toxins (33 patients), control group including PD patients without toxin exposure (78 patients). General epidemiological data and clinical data were recorded. Results: Toxin exposure was found in 33 patients (29.73%), more of them – men and rural residents. Toxin exposed PD patients had an insignificantly younger age. The most common disease phenotype in the study group was the akinetic-rigid phenotype (64.7%, p = 0.040), bradykinesia being the most common sign at the disease onset (57.6%, p = 0.008). Levodopa equivalent daily dose also was higher in the study group (659.02 ± 232.46, p = 0.042). Conclusions: Excessive exposure to toxic environmental factors may influence the clinical pattern of PD. In this study the akinetic-rigid type was the predominant disease phenotype associated with toxin exposure. Doses needed for treatment were higher in PD patients exposed to toxins, as an indicator of a more severe motor impairment in this group

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure

Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β-N-methylamino-l-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer’s disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown. Here, we evaluate BMAA exposure by investigating transcription signatures using PCR for dolphin genes homologous to those implicated in AD and related dementias: APP, PSEN1, PSEN2, MAPT, GRN, TARDBP, and C9orf72. Immunohistochemistry and Sevier Münger silver staining were used to validate neuropathology. Methylmercury (MeHg), a synergistic neurotoxicant with BMAA, was also measured using PT-GC-AFS. We report that dolphins have up to a three-fold increase in gene transcription related to Aβ+ plaques, neurofibrillary tangles, neuritic plaques, and TDP-43+ intracytoplasmic inclusions. The upregulation of gene transcription in our dolphin cohort paralleled increasing BMAA concentration. In addition, dolphins with BMAA exposures equivalent to those reported in AD patients displayed up to a 14-fold increase in AD-type neuropathology. MeHg was detected (0.16–0.41 μg/g) and toxicity associated with exposure was also observed in the brain. These results demonstrate that dolphins develop neuropathology associated with AD and exposure to BMAA and MeHg may augment these processes.

Identification of Breed Differences in Known and New Fescue Toxicosis Associated Phenotypes in Charolais-and Hereford-Sired Crossbred Beef Cows

Beef cattle phenotypes are affected by the consumption of toxic fescue. Toxic fescue’s impact is dependent on heat stress and breed composition, with genetic variability for robustness to toxin exposure believed to exist within and across breeds. The study objective was to characterize the effect of fescue toxicosis across breeds for known and novel heat and fescue stress-associated phenotypes. One-hundred crossbred fall-calving Charolais- and Hereford-sired cows of parities 1–3 were allocated to graze either toxic fescue (n = 50), non-toxic fescue (n = 25), or a rotation between toxic and non-toxic fescue (n = 25) for 156 days. Phenotypes impacted by breed (genetics) included hair coat score (p < 0.0001), hair reduction/shedding rate (p < 0.05), rectal temperature (RT) (p < 0.0001), vaginal temperature (p < 0.05), serum phosphorus concentration (p < 0.02) and respiration rate (RR) (p < 0.003). Cows on toxic fescue experienced reduced hair shedding efficacy (p < 0.0001), higher vaginal temperatures (p < 0.0001), increased systolic blood pressure (p < 0.04), increased RR (p < 0.0001) and reduced average daily gain (p < 0.0001), compared to cows grazing non-toxic fescue. Calves born from cows with higher RT during the last third of gestation had higher RT at weaning (p < 0.02), indicating potential physiological effects of in utero heat stress. The study indicates that beef cows exhibit variable responses to toxic fescue within and across breeds which may impact future calf phenotypes.

The birth-and-death evolution of cytochrome P450 genes in bees

The birth-and-death model of multigene family evolution describes how families can expand by duplication and contract by gene deletion and formation of pseudogenes. The phylogenetic stability of a gene is thought to be related to the degree of functional importance. However, it is unclear how much evolution of a gene in a gene family is driven by adaptive versus neutral processes. The cytochrome P450s are one of the most diverse and well-studied multigene families, involved in both physiological and xenobiotic functions. Bees have a high toxin exposure due to their diet of nectar and pollen, as well as the resin-collecting behavior exhibited by some bees. Here, we describe the P450s of the orchid bee Euglossa dilemma. Orchid bees are a neotropical clade in which males form perfume bouquets used in courtship displays by collecting a diverse set of volatile compounds, resulting in high chemical compound exposure. We conducted phylogenetic and selection analyses across ten bee species encompassing three bee families. We do not find a relationship between the ecology of a bee species and its P450 repertoire. Our analyses reveal that P450 clades can be classified into stable and unstable clades, and that genes involved in xenobiotic metabolism are more likely to belong to unstable clades. Furthermore, we find that unstable clades are under more dynamic evolutionary pressures, with signals of adaptive evolution detected, suggesting that both gene duplication and positive selection driving sequence divergence have played a role in the diversification of bee P450s. Our works highlights the complexity of multigene family evolution which does not always follow generalized predictions.

Memory Potential Herb: A Review

Memory is an important aspect of cognition. For its health-promoting qualities, Ayurveda is gaining popularity and attention in many areas of the globe. Dementia is a condition in which a person's mental and cognitive abilities gradually deteriorate. Dementia has been related to a number of risk factors and circumstances, including inadequate cerebral blood flow, toxin exposure, mitochondrial malfunction, and oxidative damage, and it often coexists with other neurodegenerative diseases, such as Dementia and memory loss. As a consequence, the present research focuses on the many herbal ayurvedic medicinal plants and their connection to memory functions.

Delayed, transient and self-resolving neutropenia following COVID-19 pneumonia

A novel coronaravirus, identified as SARS-CoV-2, spread throughout the world in 2020. The COVID-19 pandemic has led to many discoveries and clinical manifestations. A young patient is presented with new, self-resolving neutropenia presenting weeks after a prolonged hospital stay for COVID-19 pneumonia. Workup included analysis for underlying infection, nutritional abnormalities, malignancy, medication and toxin exposure, all of which were negative. From 2020 to the present, few reports have described neutropenia associated with a recent COVID-19 infection. In particular, no reports have described a delayed presentation of neutropenia. The authors would like to propose that the significant inflammatory response associated with COVID-19 is likely what led to this patient’s postviral neutropenia. Furthermore, in young healthy patients, bone marrow biopsy may be deferred and a watchful-waiting approach may be taken to assess for neutropenia resolution.