Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders

Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases

A review of feeding methods used in the treatment of anorexia nervosa

Background: Clear evidence based guidelines on the best and safest method of achieving and maintaining normal body weight during inpatient treatment of Anorexia Nervosa (AN) are currently not available. Oral feeding with food alone, high-energy liquid supplements, nasogastric feeding and parenteral nutrition all have the potential to achieve weight gain in the treatment of AN but the advantages and disadvantages of each method have not been comprehensively evaluated. A literature search was undertaken to identify papers describing feeding methods used during inpatient treatment of AN. The selection criteria searched for papers that described the feeding method; and reported weight change variables such as admission and discharge weight in kilograms, or Body Mass Index; or weight change over the course of inpatient treatment.\ud \ud Results: Twenty-six papers were identified, describing a total of 37 samples with a mean sample size of 58.9 participants, and a range from 6 to 318. The majority (84.6%) of papers were observational cohorts and retrospective chart reviews. The most common feeding method described was nasogastric feeding and food, then high-energy liquid supplements and food.\ud \ud Conclusions: There is limited evidence on the efficacy of feeding methods used in the refeeding and nutritional rehabilitation of AN, therefore no conclusion can be made about the most effective method of achieving weight gain during inpatient treatment. While there are a number of papers exploring this issue there is no consistency in the way the information is reported to enable comparisons between the different methods. There is an urgent need for research in this area to guide decision-making in the inpatient management, refeeding and nutritional rehabilitation of AN