BDNF val66met association with serotonin transporter binding in healthy humans.

The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [11C]DASB positron emission tomography (PET) in a comparatively large cohort of 144 healthy individuals. We used a latent variable model to determine genetic effects on a latent variable (5-HTTLV), reflecting shared correlation across regional 5-HTT binding (amygdala, caudate, hippocampus, midbrain, neocortex, putamen and thalamus). Our data supported a significant BDNF val66met effect on 5-HTTLV such that met-carriers showed 2-7% higher subcortical 5-HTT binding compared with val/val individuals (P=0.042). Our data did not support a BDNF val66met effect in neocortex and 5-HTTLPR did not significantly predict 5-HTTLV. We did not observe evidence for an interaction between genotypes. Our findings indicate that met-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT level emerges and may represent an important molecular mediator of BDNF val66met effects on behavior and related risk for neuropsychiatric illness.

Fibrogenesis imperfecta ossium with early onset: observations after 20 years of illness.

Fibrogenesis imperfecta ossium is a rare, acquired disorder of bone mineralization characterized by a morphologic abnormality of bone collagen that presents with bone pain and tenderness and usually results in the patient becoming bedridden. Onset of symptoms in the six previously reported cases of this disorder occurred in patients over 50 years of age. We report a case of fibrogenesis imperfecta ossium with symptoms starting at age 39 where the diagnosis was not made even after three bone biopsies because of the failure to recognize the characteristic morphologic abnormality of collagen. Elevated serum alkaline phosphatase, increased urinary hydroxyproline, and numerous osteoclasts on a bone biopsy are compatible with increased bone turnover. There was no apparent abnormality of vitamin D metabolism contributing to this disorder. Treatment with sodium fluoride, synthetic salmon calcitonin, and 24,25-dihydroxyvitamin D did not result in any apparent benefit.

Case report of conversion catatonia: indication for hypnosis.

The author describes the successful hypnotic treatment of a patient with an acute catatonic reaction. Because conversion mechanisms may underlie some presentations of catatonia, hypnosis may assist clinicians in the differential diagnosis of acute catatonic conditions.

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism.

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.

Early radiographic manifestations of secondary hyperparathyroidism associated with chronic renal disease.

The hands of 29 chronic dialysis patients were evaluated every 3 months for subperiosteal, intracortical, and endosteal bone resorption using fine-detail radiography and optical magnification. All patients with significant endosteal resorption also had progressive subperiosteal resorption and substantial or progressive intracortical resorption. All patients with a significantly elevated parathyroid hormone or alkaline phosphatase level had radiographic evidence of progressive bone loss. Fourteen (61%) of the 23 patients with well-controlled serum phosphate levels (mean 4.7 +/- 0.2 mg/dl) treated with supplemental calcium and dihydrotachysterol nevertheless had increased subperiosteal or endosteal resorption. Serial radiography proved to be a valuable method of evaluating progressive bone resorption.