Catatonia responsive to corticosteroids in a patient with an SCN2A variant.

Variants in SCN2A are a known risk factor for developing autism spectrum disorder (ASD). Catatonia is a complex neuropsychiatric syndrome, which occurs at a higher rate in individuals with ASD. Catatonia has also been associated with COVID-19 infection, though the majority of these cases are associated with increased serum inflammatory markers.

Influence of CYP2D6 Metabolizer Status on Risperidone and Paliperidone Tolerability in Children and Adolescents.

Risperidone and, to a lesser extent, paliperidone are metabolized by CYP2D6; however, there are limited data related to variation in CYP2D6 phenotypes and the tolerability of these medications in children and adolescents. Furthermore, the impact of CYP2D6 on the association of risperidone and paliperidone with hyperprolactinemia in youth is not well understood. A retrospective chart review was performed in psychiatrically hospitalized children and adolescents prescribed risperidone ( = 263, age = 3-18 years, mean age = 13 ± 3 years, 49% female) or paliperidone ( = 124, age = 5-18 years, mean age = 15 ± 2 years, 44% female) who had CYP2D6 genotyping performed as part of routine care.

Machine Learning-Based Prediction of Escitalopram and Sertraline Side Effects With Pharmacokinetic Data in Children and Adolescents.

Selective serotonin reuptake inhibitors (SSRI) are the first-line pharmacologic treatment for anxiety and depressive disorders in children and adolescents. Many patients experience side effects that are difficult to predict, are associated with significant morbidity, and can lead to treatment discontinuation. Variation in SSRI pharmacokinetics could explain differences in treatment outcomes, but this is often overlooked as a contributing factor to SSRI tolerability.

Pediatric Psychopharmacology for Depressive and Anxiety Disorders.

Anxiety and depressive disorders are the most common psychiatric illnesses among children and adolescents. These disorders are associated with impairments in social, family, and educational functioning. This article summarizes the evidence base for psychopharmacologic interventions; the developmental pharmacology of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); and pharmacokinetic and pharmacodynamic differences between youths and adults that call for differences in dosage and affect response and tolerability.

The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.

The neuropharmacology of marijuana, including its effects on selective serotonin reuptake inhibitor (SSRI)/antidepressant metabolism and the subsequent response and tolerability in youth, has received limited attention. We sought to (1) review clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) interactions between cannabinoids and selected SSRIs, (2) use PK models to examine the impact of cannabinoids on SSRI exposure (area under curve (AUC)) and maximum concentration (C) in adolescents, and (3) examine the frequency of adverse events reported when SSRIs and cannabinoids are used concomitantly. Cannabinoid metabolism, interactions with SSRIs, impact on relevant PK/PD pathways and known drug-drug interactions were reviewed.

The need for a refined understanding of CYP2D6 in second-generation antipsychotic outcomes in children and adolescents.

Tweetable abstract High-quality studies examining the influence of CYP2D6 on the exposure and tolerability of antipsychotics in youth are needed to mitigate the limitations of prior studies.

The neuromechanics of proleg grip release.

Because soft animals are deformable, their locomotion is particularly affected by external forces and they are expected to face challenges controlling movements in different environments and orientations. We have used the caterpillar to study neuromechanical strategies of soft-bodied scansorial locomotion. locomotion critically depends on the timing of proleg grip release, which is mediated by the principal planta retractor muscle and its single motoneuron, PPR.

Lupus risk variants in the PXK locus alter B-cell receptor internalization.

Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls.

The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls.

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects.

Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways.

Over 50 genetic variants have been statistically associated with the development of SLE (or lupus). Each genetic association is a key component of a pathway to lupus pathogenesis, the majority of which requires further mechanistic studies to understand the functional changes to cellular physiology. Whereas their use in clinical practice has yet to be established, these genes guide efforts to develop more specific therapeutic approaches.

Natural fatal Sarcocystis falcatula infections in free-ranging eagles in North America.

Three bald eagles (Haliaeetus leucocephalus) and 1 golden eagle (Aquila chrysaetos) were admitted to rehabilitation facilities with emaciation, lethargy, and an inability to fly. Intravascular schizonts and merozoites were present in 2 bald eagles, mainly in the lung tissue, whereas the third bald eagle and the golden eagle had lymphohistiocytic encephalitis with intralesional schizonts and merozoites. In all eagles, protozoal tissue cysts were present in skeletal musculature or heart.