At its December 2019 meeting, the American Psychiatric Association (APA) Board of Trustees approved "The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia." The full guideline is available at APA's Practice Guidelines website.
Summary
Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function.
Differences in cortisol levels have been found in preterm infants exposed to substantial
procedural stress during neonatal intensive care, compared to infants born full-term, but
only a few studies investigated whether altered programming of the HPA axis persists past
toddler age. Further, there is a dearth of knowledge of what may contribute to these
changes in cortisol. This prospective cohort study examined the cortisol profiles in
response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol,
in children (n=129) born at varying levels of prematurity (24–32 weeks
gestation) and at full-term (38–41 weeks gestation), at age 7 years. Further, we
investigated the relationships among cortisol levels and neonatal procedural pain-related
stress (controlling for multiple medical confounders), concurrent maternal factors
(parenting stress, depressive and anxiety symptoms) and children’s behavioral
problems. For each aim we investigate acute cortisol response profiles to a cognitive
challenge as well as diurnal cortisol patterns at home. We hypothesized that children born
very preterm will differ in their pattern of cortisol secretion from children born
full-term, possibly depended on concurrent child and maternal factors, and that exposure
to neonatal pain-related stress would be associated with altered cortisol secretion in
children born very preterm, possibly in a sex-dependent way. Saliva samples were collected
from 7-year old children three times during a laboratory visit for assessment of cognitive
and executive functions (pretest, mid-test, end - study day acute stress
profile) and at four times over two consecutive non-school days at home (i.e.
morning, mid-morning, afternoon and bedtime - diurnal
rhythm profile). We found that cortisol profiles were similar in preterm and full-term
children, albeit preterms had slightly higher cortisol at bedtime compared to full-term
children. Importantly, in the preterm group, greater neonatal procedural pain-related
stress (adjusted for morphine) was associated with lower cortisol levels on the study day
(p=0.044) and lower diurnal cortisol at home (p=0.023), with effects found
primarily in boys. In addition, child attention problems were negatively, and thought
problems were positively, associated with the cortisol response during cognitive
assessment on the study day in preterm children. Our findings suggest that neonatal
pain/stress contributes to altered HPA axis function up to school-age in children born
very preterm, and that sex may be an important factor.
Long QT interval syndrome (LQTS) type 1 (LQT1) has been reported to arise from mutations in the S3 domain of KCNQ1, but none of the seven S3 mutations in the literature have been characterized with respect to trafficking or biophysical deficiencies. Surface channel expression was studied using a proteinase K assay for KCNQ1 D202H/N, I204F/M, V205M, S209F, and V215M coexpressed with KCNE1 in mammalian cells. In each case, the majority of synthesized channel was found at the surface, but mutant IKs current density at +100 mV was reduced significantly for S209F, which showed ∼75% reduction over wild type (WT). All mutants except S209F showed positively shifted V1/2’s of activation and slowed channel activation compared with WT (V1/2 = +17.7 ± 2.4 mV and τactivation of 729 ms at +20 mV; n = 18). Deactivation was also accelerated in all mutants versus WT (126 ± 8 ms at −50 mV; n = 27), and these changes led to marked loss of repolarizing currents during action potential clamps at 2 and 4 Hz, except again S209F. KCNQ1 models localize these naturally occurring S3 mutants to the surface of the helices facing the other voltage sensor transmembrane domains and highlight inter-residue interactions involved in activation gating. V207M, currently classified as a polymorphism and facing lipid in the model, was indistinguishable from WT IKs. We conclude that S3 mutants of KCNQ1 cause LQTS predominantly through biophysical effects on the gating of IKs, but some mutants also show protein stability/trafficking defects, which explains why the kinetic gain-of-function mutation S209F causes LQT1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.