Animal models early life stress

Similar to findings in animal models of early-life stress, elevated 24-hour urinary NE, epinephrine (E), and dopamine (DA) excretion as well as decreased platelet adrenergic receptors have been measured in abused children with PTSD (Perry, 1994 DeBellis et al., 1999a). Abused children with PTSD also exhibit... 

A number of studies have repeatedly measured increased CRF-like immunoreactivity in the CSF of untreated patients with major depression (e.g., Nemeroff et ah, 1984). A recent study using serial CSF sampling over 30 hours has provided evidence for inadequately high CRF activity in major depression in the face of sustained hypercortisolism (Wong et ah, 2000). Postmortem studies have further provided evidence for increased CRF concentrations and CRF mRNA expression in hypothalamic tissue of depressed patients as well as decreased CRF receptor binding, likely due to chronic CRF hypersecretion, in the frontal cortex of suicide victims (Nemeroff et ah, 1988 Raadsheer et ah, 1994, 1995). These findings are consistent with indices of increased CRF activity in the hypothalamus and other structures in animals models of early-life stress. Direct measures of central CRF release in humans with early-life stress are still unavailable. 

Interestingly, while peripheral neuroendocrine function appears normal in patients with panic disorder, decreased basal cortisol concentrations have been reported in most studies in PTSD patients. This relative hypocortisolism occurs in the context of increased feedback inhibition of the HPA axis (see Yehuda, 2000). However, a dissociation between central and adrenocortical (re)activity has been found in animal models of severe early-life stress as well as in abused children and women, suggesting that adrenal dysfunction may, at least in part, contribute to hypocortisolism in PTSD. In the face of hypocortisolism, it seems surprising that hippocampal atrophy is one of the most prominent findings in patients with PTSD, including adult survivors of childhood abuse with PTSD (see Newport and Nemeroff, 2000). While increased glucocorticoid sensitivity of hippocampal cells may play a role in the development of hippocampal atrophy, another potential mechanism may involve toxic effects of markedly increased cortisol responses to everyday stress in patients with PTSD. 

The third part. Developmental Psychopathology, delves into detailed disease-specific overviews. Each of the chapters covers issues pertaining to nosology and classification, to genetic determinants, brain systems implicated, environmental influences, and nature-nurture interactions. Neurotransmission and neuromodulation, and hormonal and other developmental influences are addressed and, whenever available, relevant animal models are incorporated into the discussion. The interplay of normative and derailed development is a core concept for these chapters. Of the part s 12 chapters, 9 are devoted to traditionally defined disease categories, and 3 cover the overarching areas of early-life stress, aggression, and affiliative behaviors. 

Lyons, D.M., Parker, K.J., Schatzberg, A.R, 2010. Animal models of early life stress implications for understanding resilience. Dev. Psychobiol. 52, 616-624. 

The first inflammatory stage of atherosclerosis starts early in life with more severe lesions developing only if classical risk factors, especially cholesterol, remain present. Immune responses mounted against antigens cross-react with homologous host proteins in a form of molecular mimicry, for example, HSP are secreted by C. pneumoniae, H. pylori, mammalian vascular cells exposed to stress such as CVD risk factors, and cells within atherosclerotic plaques In addition, serum titers of anti-HSP antibodies are correlated positively with the future risk of CHD, and purified anti-HSP antibodies lyse stressed human EC and macrophages in vitro. Furthermore, immunization with HSP exacerbate athersclerosis in animal models (reviewed in refs. 212,213). However, there is molecular mimicry between epitopes of oxLDL and Streptococcus pneumonia in LDLR -/- mice pneumococcal immunization led to increased IgM levels against oxLDL and decreased the extent of atherosclerosis (214). 

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