Overlapping characteristics between human depressive phenotypes and mouse behaviors has led to the creation of mouse models that aim to investigate the pathophysiology and treatment of unipolar depression. Behavioral tests in mice are used to assess and quantify the extent to which a mouse model displays a depression-like phenotype. The forced swim test and tail suspension test, sucrose preference test, and novelty suppressed feeding tests all aim to measure different components of depression. However, each one of these tests has different strengths and weaknesses in terms of predictive, face and construct validities. Furthermore, the responses to these tests vary greatly depending on strain of mouse. Depression-related behavioral tests are an extremely useful investigative tool in unearthing causes and predicting treatment outcomes in human depression, but as this review demonstrates, the comprehension of the finer details are extremely important in the design, analysis, and evaluation of such mouse studies. Curr. Protoc. Mouse Biol. 2:119-127 © 2012 by John Wiley & Sons, Inc.

Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. Here, we report that Chd8 heterozygous mice display subtle brain hyperplasia shortly after birth, hypertelorism, early motor delay, pronounced hypoactivity and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at mid-gestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the down-regulated transcripts. Restingstate functional MRI identified increased synchronised activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioural phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring result in distinctive anomalies in functional brain connectivity in Chd8 +/-mice. Human imaging studies have consistently found evidence for changes in functional connectivity in ASD cohorts, most commonly long-range under-connectivity. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/143552 doi: bioRxiv preprint first posted online May. 29, 2017; 3 SIGNIFICANCE STATEMENTDe novo mutations in the chromatin remodeling factor CHD8 cause ASD with high penetrance, making CHD8 one of the leading ASD candidate genes. We established a Chd8 heterozygous mouse model that recapitulates anatomical phenotypes seen in patients with CHD8 haploinsufficiency and displays a unique complement of behavioural phenotypes.Increased functional connectivity observed in cortical and hippocampal areas suggests that neuropsychiatric phenotypes associated with CHD8 deficiency may be the result of distinct connectivity changes. Transcriptomic analyses highlighted dysregulation of axon guidance genes as a possible underlying mechanism. Together, our data suggest that CHD8 haploinsufficiency represents a distinct ASD subtype characterised by a unique set of anomalous behaviours, including increased responsiveness to social stimuli, and functional connectivity changes in mice.not peer-reviewed)

There is significant evidence for genetic factors in the susceptibility to anorexia nervosa (AN). Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found. In the present study variation in the estrogen receptor 1 (ESR1) and ESR2 genes was examined. Estrogen receptors have been localised to areas of the brain involved in behaviour and regulation of food intake. The anorexic effects of estrogen are accentuated by stress and thus it is postulated that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. A cohort of 170 female, Caucasian AN sufferers and 152 female controls were typed for dinucleotide repeat polymorphisms in both ESR1 and ESR2 and two further SNPs at each locus. Variation at ESR1 was not associated with AN. However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed. Analysis of haplotypes at ESR1 and ESR2 showed no significant evidence of association with AN suggesting that the variability in ESR2 alone may contribute to the genetic susceptibility to AN.