Effects of Mineralocorticoid Receptor Overexpression on Anxiety and Memory after Early Life Stress in Female Mice

Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice

Hypothyroidism in an Area of Endemic Goiter and Cretinism in Central Java, Indonesia

In an area of severe endemic goiter in Central Java, Indonesia, clinical overt or mild hypothyroidism appeared to be present in 7 out of 20 cretins and also in 12 out of 94 non-cretinous subjects, all 5–20 years of age, living in the village of Sengi. Hypothyroidism was not found in a control group of 70 subjects of the same age living in Londjong just outside the edemia. In hypothyroid subjects the plasma PBI-concentration was 0.98 ± 0.32 µg/100 ml (mean ± SD) vS 2.72 ± 1.24 µg/100 ml in euthyroid subjects from Sengi and 4.86 ± 0.80 µg/100 ml in controls from Londjong. Values for T3 were 56.3 ± 31.7 ng/100 ml in hypothyroids, 140.5 ± 38.5 ng/100 ml in euthyroids from Sengi and 121.6 ± 27.4 ng/100 ml in controls. The TSH levels (geometric mean and range) in these 3 groups were, respectively, 210.1 (108.0–342), 15.6(3.0– 372) and 4.1 (0.8–7.0) µU/ml. The differences between themean concentration of PBI, T3 and TSH in the hypothyroid and euthyroid groups were highly significant (P < 0.001). These data strengthen the clinical diagnosis of hypothyroidism in cretins as well as in non-cretinous subjects. All hypothyroid subjects had a PBI < 1.8 µg/100 ml and T3 < 120 ng/100 ml and TSH < 100 µU/ml. In 8 hypothyroid subjects, restudied 18 months after iodized oil injection, hypothyroidism was either corrected or markedly improved. It therefore appears that iodine deficiency per se in post natal life may lead to (juvenile) hypothyroidism, which can be corrected by iodine therapy. Our findings have implications for the definition and diagnosis of endemic cretinism. Not all hypothyroid subjects in an area of endemic iodine deficiency should be classified as cretins