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.     

The factor structure of the CVLT-C in pediatric epilepsy.

The current study used archival data to evaluate the fit of six latent variable models, originally generated by Donders (1999), for the California Verbal Learning Test-Children's Version (CVLT-C; Delis, Kramer, Kaplan, & Ober, 1994) in a large (N = 289) sample of pediatric epilepsy cases presenting at three tertiary treatment centers. Using confirmatory factor analysis, we found that a model including factors of Attention Span, Learning Efficiency, Free Delayed Recall, Cued Delayed Recall, and Inaccurate Recall demonstrated the best relative fit for our data. These findings are consistent with those reported by Donders (1999) in his reanalysis of the CVLT-C standardization sample data, supporting the validity of this factorial model in pediatric epilepsy populations.     

A Nonverbal Learning Disability in a Case of Central Hypoventilation Syndrome without a PHOX2B Gene Mutation

This study examines the neuropsychological profile of a boy with congenital central hypoventilation syndrome (CCHS) without a paired-like homeobox gene (PHOX2B) mutation. CCHS is a rare disorder of autonomic nervous system development characterized by an impaired ventilatory response to hypercarbia and hypoxemia. Mild intellectual deficits are common but a specific cognitive profile is not established in CCHS. We describe a nonverbal learning disorder as a CCHS endophenotype and recommend that detailed neuropsychological testing be performed on all individuals with CCHS. Defining the psycho-educational needs in CCHS may avert compounding the emotional and medical stresses of this already debilitating disorder.     

Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adrenocorticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.     

The Factor Structure of the CVLT-C in Pediatric Epilepsy

The current study used archival data to evaluate the fit of six latent variable models, originally generated by Donders (1999) Donders. 1999. Structural analysis of the California Verbal Learning Test—Children's Version in the standardization sample. Developmental Neuropsychology, 15(3): 395–406. [CSA][Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], for the California Verbal Learning Test-Children's Version (CVLT-C; Delis, Kramer, Kaplan, &; Ober, 1994 Delis, D. C., Kramer, J. H., Kaplan, E. and Ober, B. A. 1994. California Verbal Learning Test—Children's Version, San Antonio, TX: Psychological Corporation.  [Google Scholar]) in a large (N = 289) sample of pediatric epilepsy cases presenting at three tertiary treatment centers. Using confirmatory factor analysis, we found that a model including factors of Attention Span, Learning Efficiency, Free Delayed Recall, Cued Delayed Recall, and Inaccurate Recall demonstrated the best relative fit for our data. These findings are consistent with those reported by Donders (1999) Donders. 1999. Structural analysis of the California Verbal Learning Test—Children's Version in the standardization sample. Developmental Neuropsychology, 15(3): 395–406. [CSA][Taylor &; Francis Online], [Web of Science ®] , [Google Scholar] in his reanalysis of the CVLT-C standardization sample data, supporting the validity of this factorial model in pediatric epilepsy populations.     

Cognitive and behavioral functioning in Coffin-Siris syndrome and epilepsy: a case presentation

The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS.