Literature Collection

Unique from other fetal anatomical systems, the central nervous system (CNS) starts development early in the embryonic period shortly after fertilization before most patients are even aware they are pregnant. Maturation throughout pregnancy involve complicated structural and functional changes, most likely below the resolution of testing to detect. During this time, the fetal CNS is susceptible to lesions that reflect trimester-specific adverse events. Neonatal neurological status with childhood sequelae can result from combinations of antenatal, peripartum and neonatal adverse events. Person-specific clinical management choices must consider the timing of multiple mechanisms that can alter neurodevelopment including genetic causes, aetiologies after conception as well as communicable and non-communicable conditions that result in anomalous or destructive brain lesions. The appearance of the fetal brain also changes significantly through gestation as different structures mature and the cerebral cortex in particular increases in size and complexity. Therefore, obstetrical imagers and maternal fetal medicine physicians need to be aware of the expected evolving appearances of the healthy fetal brain as the fetus advances in gestation. Often when fetal CNS pathology is detected or anticipated during pregnancy, there is understandably significant parental anxiety regarding the long-term implications of their child's neurodevelopmental prognosis. In these instances, Maternal Fetal Medicine specialists often collaborate with Pediatric Neurologists in the antenatal period regarding diagnoses that anticipate neonatal or later childhood neurologic sequelae. Potential adverse outcomes are discussed with prospective parents to be integrated into choices based on shared decisions.

The leaves of Mitragyna speciosa (kratom), a plant native to Southeast Asia, are increasingly used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that metabolism of kratom's major alkaloid, mitragynine, in mice leads to formation of (a) a potent mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A-mediated pathway, which exhibits reinforcing properties, inhibition of gastrointestinal (GI) transit and reduced hyperlocomotion, (b) a multifunctional mu agonist/delta-kappa antagonist, mitragynine pseudoindoxyl, through a CYP3A-mediated skeletal rearrangement, displaying reduced hyperlocomotion, inhibition of GI transit and reinforcing properties, and (c) a potentially toxic metabolite, 3-dehydromitragynine, through a non-CYP oxidation pathway. Our results indicate that the oxidative metabolism of the mitragynine template beyond 7-hydroxymitragynine may have implications in its overall pharmacology in vivo.

BACKGROUND: The prevalence of methamphetamine use disorder (MUD) in the United States has risen dramatically in the past four decades and is concentrated in populations such as men who have sex with men (MSM). Despite the public health consequences of MUD, there are no FDA-approved psychopharmacological treatments. Psychosocial treatment alone has been shown to reduce methamphetamine use, but high attrition rates limit treatment efficacy. Promising findings from animal models of MUD using exogenous oxytocin, a social neuropeptide, have set the stage for translational work. Along with unique anti-addiction effects, oxytocin holds a primary role in enhancing social salience and modulating stress. In humans, oxytocin administration, combined with evidence-based psychosocial interventions, may act synergistically to improve addiction treatment outcomes and improve retention rates in current MUD treatment. METHODS/DESIGN: We are conducting a randomized, double-blind, placebo-controlled trial of oxytocin-enhanced motivational interviewing group therapy (MIGT). Oxytocin or placebo 40 IU is administered intranasally in conjunction with six, weekly MIGT sessions. We will recruit 50 MSM, initiating treatment for MUD from specialized community health programs in San Francisco, CA, USA. Individuals will be randomized (1:1) to receive six, weekly sessions of MIGT with or without oxytocin. Our primary outcome is session attendance. Other outcomes of interest include: measures of group cohesion, anxiety, psychophysiology, and stimulant craving and use. DISCUSSION: This will be the first study of oxytocin's effects in humans with MUD. Findings from this novel protocol will attempt to bridge existing animal data with the need for innovative clinical treatments for MUD, inform the growing field of pharmacologically-enhanced psychotherapy, and help to elucidate mechanisms behind oxytocin's potential anti-addiction effects. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02881177 . Registered on 26 August 2016.

BACKGROUND: The p factor represents the overall liability for the development of mental illness. While evidence supporting the p factor in adults has been reported, studies in children are fewer, and none have examined the p factor in children with chronic physical illness (CPI). OBJECTIVE: We aimed to model the p factor in a longitudinal sample of children with CPI using a parent-reported checklist and examine its construct validity against a structured diagnostic interview. METHODS: We used data from 263 children aged 2-16 years diagnosed with a CPI who were enrolled in the Multimorbidity in Children and Youth across the Life-course (MY LIFE) study. The p factor was modelled using the Emotional Behavioural Scales over 24 months using confirmatory factor analysis. Validation of the p factor was set against the Mini International Neuropsychiatric Interview for Children and Adolescents. RESULTS: Factorial evidence supported the p factor, modelled using a bi-factor structure, compared to a standard correlated-factors (i.e., two-factor) structure [Δχ(2) = 9.66(4), p = 0.047]. p factor scores were correlated with the number of different mental illness diagnoses (r = 0.71) and total number of diagnoses (r = 0.72). Dose-response relationships were shown for the number of different diagnoses (p < 0.001) and total number of diagnoses (p < 0.001). CONCLUSION: In this first study of the p factor in children with CPI, we showed evidence of its bi-factor structure and associations with mental illness diagnoses. Mental comorbidity in children with CPI is pervasive and warrants transdiagnostic approaches to integrated pediatric care.