Neuroendocrine strategies in affective disorders

1. 1. Neuroendocrine strategies in affective disorders have explored both resting values of hormones and hormonal responses to stimuli such as hypoglycemia, TRH, LHRH, dexamethasohe, methadone and morphine. The abnormalities established to date have involved growth hormone, cortisol and TSH responses in particular. Prolactin has not been investigated to the same extent. We therefore describe several prolactin studies exemplifying selected neuroendocrine strategies.

2. 2. Our studies of prolactin responses included acute cases of either primary or secondary depression, stabilized bipolar patients, and healthy controls both off and on lithium. We found prolactin response to hypoglycemia significantly reduced in primary but not secondary depressions.

3. 3. Lithium administration led to flattened prolactin responses to hypoglycemia in stabilized bipolar patients but not in healthy controls. The flattened response in patients was observed already after 3 weeks of lithium, and remained flattened after years of treatment. The findings suggest a greater degree of prolactin reponse reduction in those patients showing most pronounced stability on lithium treatment.

Lithium isotopes: differential effects on renal function and histology

Objectives: Reduction in renal concentrating ability has been reported in patients undergoing chronic lithium treatment. Prior work has demonstrated differences in physiological effects of the stable lithium isotopes, ⁶Li and ⁷Li. Here, we measured the degree of polyuria, polydipsia and kidney histological changes induced in rats by equimolar amounts of ⁶LiCl, ⁷LiCl and the commercially available mixture of both isotopes.

Methods: Rats were given 1.0 mEq/kg of either ⁶LiCl, ⁷LiCl or ‘ⁿLiCl’ (isotope mixture, 93% ⁷LiCl) by subcutaneous injection twice daily for up to 49 days. Twenty‐four‐hour urine volume and water intake were measured daily. Kidneys from rats treated for 7 days with 1.5 mEq/kg ⁶LiCl, ⁷LiCl and vehicle were examined under light microscopy and histopathologic changes graded on a 4‐point scale of severity.

Results: All rats showed loss in renal concentrating ability manifested by increasing urine volume and water intake. Peak effects occurred after 9–13 days treatment, then declined to stable levels at two to three times pre‐treatment level. Mean peak effect was significantly greater for ⁶LiCl than for ⁷LiCl. Chronic effects of ⁶LiCl (weeks 3–7 of treatment) on polyuria and polydipsia were persistently higher than that of ⁷LiCl. ⁿLiCl effect was intermediate. Kidneys from rats treated for 7 days with ⁶LiCl showed more frequently severe lesions in renal tubules than did ⁷LiCl‐treated rats.

Conclusions: Our current data and prior studies suggest that elimination or reduction of ⁶Li from pharmaceutical preparations may merit further evaluation as a possibly less potentially nephrotoxic form of lithium treatment.     

Gonadal steroid hormones and the hypothalamo–pituitary–adrenal axis

The hypothalamo–pituitary–adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, prior to generating an appropriate response is the animal’s reproductive status. Thus, PVN neurons express androgen and estrogen receptors and receive input from sites that also express these receptors. Consequently, changes in reproduction and gonadal steroid levels modulate the stress response and this underlies sex differences in HPA axis function. This review examines the make up of the HPA axis and hypothalamo–pituitary–gonadal (HPG) axis and the interactions between the two that should be considered when exploring normal and pathological responses to environmental stressors.     

Electroconvulsive therapy,depression, the immune system and inflammation: A systematic review

Background

The management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.