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CONTEXT Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics. OBJECTIVE To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22(More)
BACKGROUND Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown. OBJECTIVE To evaluate the effect of leptin on neurocognitive development. METHODOLOGY A 5-year-old boy with a nonconservative(More)
Leptin replacement rescues the phenotype of morbid obesity and hypogonadism in leptin-deficient adults. However, leptin's effects on insulin resistance are not well understood. Our objective was to evaluate the effects of leptin on insulin resistance. Three leptin-deficient adults (male, 32 yr old, BMI 23.5 kg/m(2); female, 42 yr old, BMI 25.1 kg/m(2);(More)
To describe our 10-year experience in treating leptin-deficient humans. Three adults and one boy presented with childhood-onset morbid obesity, hypogonadism and family history of obesity and early death. Serum leptin was inappropriately low. A recessive C105T leptin gene mutation was identified. Metabolic and endocrine assessments were conducted, before and(More)
DEFICITS IN NEUROPLASTICITY ARE HYPOTHESIZED TO UNDERLIE THE PATHOPHYSIOLOGY OF MAJOR DEPRESSIVE DISORDER (MDD): the effectiveness of antidepressants is thought to be related to the normalization of disrupted synaptic transmission and neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has received considerable attention for its role(More)
A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During(More)
The hormone leptin profoundly affects body weight and metabolism. Three human adults (two women, 35 and 40 yr old; one man, age 27) have been identified with a recessive mutation in the ob gene, which is homologous to the mutation in ob/ob mice, and produces leptin deficiency and morbid obesity. Because leptin replacement increases brain weight and changes(More)
BACKGROUND To study the potential association of antidepressant use and suicide at a population level, we analyzed the associations between suicide rates and dispensing of the prototypic SSRI antidepressant fluoxetine in the United States during the period 1960-2002. METHODS AND FINDINGS Sources of data included Centers of Disease Control and US Census(More)
There has been considerable promise and hope that pharmacogenomics will optimize existing treatments for major depression, as well as identify novel targets for drug discovery. Immediately after the sequencing of the human genome, there was much hope that tremendous progress in pharmacogenomics would rapidly be achieved. In the past 10 years this initial(More)
The hypothesis that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of major depression is supported by several research findings; however, genetic studies assessing the relationship between BDNF and psychiatric disorders have produced conflicting results. We examined the effect of a BDNF polymorphism on depression susceptibility in(More)