Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.     

Problem Behavior in Children of Chronically Ill Parents: A Meta-Analysis

The aim of this meta-analysis is to examine whether children of chronically ill parents differ from norm groups in problem behavior. We report moderator effects and overall effect sizes for internalizing, externalizing and total problem behavior assessed by children and parents. In fixed effect models, we found a significant overall effect size for internalizing problem behavior (number of studies k = 19, total sample size N = 1,858, Cohen’s d = .23, p < .01) and externalizing problem behavior (k = 13, N = 1,525, d = .09, p < .01) but not for total problem behavior (k = 7; N = 896). Effects for internalizing and externalizing problem behavior were larger in non-cancer studies, in samples including younger children and younger ill parents, in samples defined by low average SES and in studies including parents with longer illness duration. In addition, effects for externalizing problem behavior were larger in studies characterized by a higher percentage of ill mothers and single parents. With exclusive self-report, effect sizes were significant for all problem behaviors. Based on these results, a family-centered approach in health care is recommended.     

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.     

Differential Outcomes of Adolescents with Chronically Ill and Healthy Parents

Approximately 10% of children grow up with a parent who has been diagnosed with a chronic medical condition (CMC) and seem to be at risk for adjustment difficulties. We examined differences in behavioral, psychosocial and academic outcomes between 161 adolescents from 101 families with a chronically ill parent and 112 adolescents from 68 families with healthy parents, accounting for statistical dependence within siblings. Children between 10 and 20 years and their parents were visited at home and filled in questionnaires. Multilevel analyses showed that 20–60% of the variance in most adolescent outcomes was due to the family cluster effect, especially in internalizing problem behavior, caregiving variables and quality of parent attachment. Conversely, the variance in stress and coping variables and grade point average (GPA) was mainly due to individual characteristics. Adolescents with parents affected by CMC displayed more internalizing problems than the comparison group and scored higher on frequency of household chores, caregiving responsibilities, activity restrictions, isolation, daily hassles and stress. In addition, their grade point average was comparatively worse. No group differences in externalizing problems, coping skills and quality of parent attachment were found. In conclusion, the family cluster effect largely explains adolescent outcomes and should be accounted for. Adolescents with parents affected by CMC are subject to an increased risk for internalizing problems, adverse caregiving characteristics, daily hassles, stress and a low GPA. According to a family-centered approach, school counselors and health care practitioners should be alert to adjustment difficulties of children with a chronically ill parent.