Stefan Wüst

The aim of the present study was to determine the association between prenatal stress and immune function in human adults. Peripheral blood mononuclear cells (PBMCs) from 34 healthy young women whose mothers experienced major negative life events during their pregnancy (Prenatal Stress, PS group, mean age 25, SD ± 4.34 years), and from a female comparison group (n = 28, CG, mean age 24 ± 3.40 years), were stimulated with phytohemagglutinin (PHA), and subsequent cytokine production was measured. A bias for T‐helper 2 (Th2) cytokine production due to an overproduction of IL‐4 relative to IFN‐γ after PHA stimulation was observed in PS subjects. In addition, IL‐6 and IL‐10 were also significantly elevated. To the best of our knowledge, this study is the first to suggest a direct association between prenatal stress exposure and alterations in immune parameters in adult women. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 579–587, 2008.

Abstract: From the perspective of psychobiological stress research we present a brief overview of findings documenting a significant impact of genetic factors on the activity of the hypothalamus‐pituitary‐adrenal (HPA) axis. Quantitative genetic studies in twins as well as association studies, primarily on polymorphisms in the glucocorticoid receptor gene, are depicted. Recent findings suggest that the collaboration of psychobiology and molecular genetics is a promising interdisciplinary approach that will significantly contribute to the understanding of the mechanisms underlying the link between stress, the HPA axis, and HPA‐related clinical states.

Chronic dysregulation of hypothalamus-pituitary-adrenal axis activity is related to several stress-related disorders. Evidence suggests that polymorphisms in the glucocorticoid receptor (GR) gene may have an impact on this neuroendocrine system. In the present investigation, 112 healthy males were studied to estimate the impact of three GR gene polymorphisms (BclI RFLP, N363S, ER22/23EK) on cortisol and ACTH responses to psychosocial stress (Trier Social Stress Test) and pharmacological stimulation (1 microg ACTH(1-24), 0.5 mg dexamethasone). Because only four ER22/23EK heterozygotes were identified, these subjects were not statistically analyzed. Compared with subjects with the wild-type GR genotype (n = 36), 363S allele carriers (n = 10) showed significantly increased salivary cortisol responses to stress, whereas the BclI genotype GG (n = 18) was associated with a diminished cortisol response. BclI heterozygotes and homozygotes (GG) exhibited a trend toward lower ACTH responses, compared with wild-type subjects and 363S carriers. The cortisol response to ACTH(1-24) administration was not significantly different between genotypes. After dexamethasone ingestion, 363S carriers showed a trend toward an enhanced cortisol suppression. This is the first report documenting an impact of GR gene polymorphisms on cortisol (and perhaps ACTH) responses to psychosocial stress. These variants may contribute to the individual vulnerability for hypothalamus-pituitary-adrenal-related disorders.