Effects of psycho-social stress during pregnancy on neuroendocrine and behavioural parameters in lactation depend on the genetically determined stress vulnerability

The neuroendocrine consequences of repeated exposure of the pregnant mother to relevant stressors have been studied in the offspring, but not in the mothers. As these stress effects might depend on the genetically determined stress susceptibility of the dams, here, we investigated the effects of daily exposure to psycho-social stressors (maternal defeat by an aggressive lactating resident and restraint) between pregnancy days 4 and 18 in female rats selectively and bidirectionally bred for high (HAB) or low (LAB) anxiety-related behaviour. ACTH and corticosterone secretory responses to a mild stressor were found to be low in unstressed lactating HAB and LAB dams (day 8 of lactation) indicating an intact physiological attenuation of the HPA axis at this time. Pregnancy stress significantly increased the reactivity of the hypothalamo-pituitary-adrenal (HPA) axis in lactating HAB, but not LAB rats, reflecting impaired attenuation of the HPA axis selectively in pregnancy-stressed HAB dams. The high and low anxiety phenotypes were consistent in lactation and not significantly altered by pregnancy stress, despite an elevated level of arousal in pregnancy-stressed HAB dams. In general, HAB dams showed signs of a more protective maternal behaviour compared to LAB dams: (i) in the home cage, HAB dams spent more time in direct pup contact (day 1 of lactation), (ii) during two forms of the pup retrieval test, differing in the level of challenging the dam, HAB dams retrieved the pups faster, and (iii) during the maternal defence test, they were more aggressive towards a virgin intruder compared to LAB and NAB dams. Pregnancy stress did not alter any of these behavioural measures, except an increase in the speed of pup collection in a novel environment in HAB dams and increased maternal aggression in LAB dams. The results indicate a robust behavioural phenotype of HAB and LAB dams with respect to anxiety and maternal behaviour which was found to be almost unchanged by exposure to pregnancy stress. However, the finding of differential effects of pregnancy stress on the attenuation of the reactivity of the HPA axis in lactation makes HAB and LAB rats a potential animal model for studying genetically determined differences in stress vulnerability and stress-induced maladaptation of the HPA axis post-partum.     

Evidence for a neural correlate of a framing effect: bias-specific activity in the ventromedial prefrontal cortex during credibility judgments

BACKGROUND: Neural processes within the medial prefrontal cortex play a crucial role in assessing and integrating emotional and other implicit information during decision-making. Phylogenetically, it was important for the individual to assess the relevance of all kinds of environmental stimuli in order to adapt behavior in a flexible manner. Consequently, we can in principle not exclude that environmental information covertly influences the evaluation of actually decision relevant facts ("framing effect"). OBJECTIVE: To test the hypothesis that the medial prefrontal cortex is involved into a framing effect we employed functional magnetic resonance imaging (fMRI) during a binary credibility judgment task. METHODS: Twenty-one subjects were asked to judge 30 normalized news magazine headlines by forced answers as "true" or "false". To confound the judgments by formally irrelevant framing information we presented each of the headlines in four different news magazines characterized by varying credibility. For each subject the susceptibility to the judgment confounder (framing information) was assessed by magazine-specific modifications of the answers given. RESULTS: We could show that individual activity changes of the ventromedial prefrontal cortex during the judgments correlate with the degree of an individual's susceptibility to the framing information. CONCLUSION: We found (i) a neural correlate of a framing effect as postulated by behavioral decision theorists that (ii) reflects interindividual differences in the degree of the susceptibility to framing information.     

Memory of early maltreatment: neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning.

BACKGROUND: While children form an attachment to their abusive caregiver, they are susceptible to mental illness and brain abnormalities. To understand this important clinical issue, we have developed a rat animal model of abusive attachment where odor paired with shock paradoxically produces an odor preference. Here, we extend this model to a seminaturalistic paradigm using a stressed, "abusive" mother during an odor presentation and assess the underlying learning neural circuit. METHODS: We used a classical conditioning paradigm pairing a novel odor with a stressed mother that predominantly abused pups to assess olfactory learning in a seminaturalistic environment. Additionally, we used Fos protein immunohistochemistry to assess brain areas involved in learning this pain-induced odor preference within a more controlled maltreatment environment (odor-shock conditioning). RESULTS: Odor-maternal maltreatment pairings within a seminatural setting and odor-shock pairings both resulted in paradoxical odor preferences. Learning-induced gene expression was altered in the olfactory bulb and anterior piriform cortex (part of olfactory cortex) but not the amygdala. CONCLUSIONS: Infants appear to use a unique brain circuit that optimizes learned odor preferences necessary for attachment. A fuller understanding of infant brain function may provide insight into why early maltreatment affects psychiatric well-being.     

Results of Three Dimensional Conformal Radiotherapy and Hormonal Therapy for Local Recurrence after Radical Prostatectomy

Background and Purpose: Analysis of treatment results of combined three–dimensional conformal radiotherapy (3DCRT) and hormonal therapy in patients with locally recurrent prostate cancer after radical prostatectomy.Patients and Methods: Between 1992 and 1998, 24 patients presented with a rising prostate–specific antigen (PSA) between 4 and 152 months following radical prostatectomy and a local recurrence demonstrated by imaging. Recurrence was biopsy–proven in 13 cases. All patients were treated with 3DCRT to a total dose of 60–70 Gy. 21 patients (88%) received adjuvant hormone therapy up to a maximum of 6 months.Results: All patients showed a response in PSA values after therapy. Median follow–up is 43 months. Overall survival is 80% and 67% at 3 and 5 years, respectively. Biochemical control rates are 53% and 38% at 3 and 5 years, respectively. 14 patients developed a second PSA relapse. Acute and late toxicities, classified with the RTOG score, were moderate.Conclusion: Radiotherapy and short–term adjuvant hormone therapy represent an effective and well–tolerated treatment for locally recurrent prostate cancer after radical prostatectomy resulting in good local control. Long–term prognosis in terms of biochemical control and disease–specific survival remains poor.