Adverse childhood experiences and child-to-adult height trajectories in the 1958 British birth cohort

Background Adverse childhood experiences (maltreatment and household dysfunction) are associated with adult cardiovascular disease (CVD). One possible pathway is through physical development, which has been linked to CVD risk. Our aim was to examine whether adverse childhood experiences are associated with child-to-adult height trajectories. Method The 1958 British birth cohort (n=17 638) includes all born in one week in March 1958, followed up to mid adulthood. Height was measured at 7, 11 and 16 years (y) and adulthood (converted to standard deviation scores (SDS);≥1 height measurement n=16 444, adult leg length n=9180). Multivariate response models were used to examine the associations between childhood experiences (ascertained at 7 y and self-reported at 45 y) and child-to-adult height. Results Childhood neglect, prospectively assessed at 7 y, was associated with shorter stature throughout childhood: for each increment across a score ranging 0-7, average height reduced by 0.06 SDS (males) and 0.05 SDS (females) at 7 y (≈0.3 cm), with smaller deficits (0.03 SDS, ≈0.2 cm) in adulthood, after adjustment for parental height, birthweight and socio-economic factors. In males, the adult deficit was mainly due to shorter leg length. Household dysfunction was associated with shorter stature at 7-11 y, with adjusted deficits from 0.04 to 0.07 SDS per increment across a score ranging 0-7, but not at later ages. Adjusted models showed no associations for retrospectively reported abuse or neglect to 16 y. Conclusions Those with a higher neglect score by 7 y grew more slowly, with deficits through to adulthood. No associations were found for abuse over the longer period to 16 y. Deficits associated with early life neglect and household dysfunction might have implications for adult CVD risks.</p

Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons

Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS-R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS-R is located on growth hormone-releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin-induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin-induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin-releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin-induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch-clamp recordings on mouse GHRH-enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS-R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS-R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion