Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity.

Clinic-based retrospective analysis of psychopharmacology for behavior in fragile x syndrome.

Fragile X syndrome (FXS) is associated with behavior that limits functioning, including distractibility, hyperactivity, impulsivity, hyperarousal, anxiety, mood dysregulation, and aggression. Medication response and side effect data were reviewed retrospectively for 257 patients (age 14 ± 11 years, range 4-60 years, 203 M, 54 F) attending an FXS clinic. Treatment success rates were defined as the percentage of positive response in the form of documented clinical report of improvement in the behavior(s) being targeted over at least a 6-month period on the medication, without side effects requiring medication discontinuance, while failures were defined as discontinuance of medication due to lack of clinical effectiveness or side effects.

Fibroblast phenotype in male carriers of FMR1 premutation alleles.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder among carriers of premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The clinical features of FXTAS, as well as various forms of clinical involvement in carriers without FXTAS, are thought to arise through a direct toxic gain of function of high levels of FMR1 mRNA containing the expanded CGG repeat. Here we report a cellular endophenotype involving increased stress response (HSP27, HSP70 and CRYAB) and altered lamin A/C expression/organization in cultured skin fibroblasts from 11 male carriers of premutation alleles of the FMR1 gene, including six patients with FXTAS and five premutation carriers with no clinical evidence of FXTAS, compared with six controls.

Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome.

Objective: In fragile X syndrome (FXS), it is hypothesized that absence of the fragile X mental retardation protein (FMRP) disrupts regulation of group 1 metabotropic glutamate receptor (mGluR and mGluR5)-dependent translation in dendrites. Lithium reduces mGluR-activated translation and reverses phenotypes in the dfxr mutant fly and fmr1 knockout mouse. This pilot add-on trial was conducted to evaluate safety and efficacy of lithium in humans with FXS.

Early-phase ERK activation as a biomarker for metabolic status in fragile X syndrome.

Lack of production of the Fragile X Mental Retardation Protein (FMRP) leads to changes in dendritic morphology and resultant cognitive and behavioral manifestations characteristic of individuals with Fragile X syndrome (FXS). FMRP is an RNA-binding protein that is believed to regulate the translation of a large number (probably over 100) of other proteins, leading to a complex and variable set of symptoms in FXS. In a mouse model of FXS, we previously observed delayed initiation of synaptically localized protein synthesis in response to neurotransmitter stimulation, as compared to wild-type mice.

Characterization of potential outcome measures for future clinical trials in fragile X syndrome.

Clinical trials targeting recently elucidated synaptic defects in fragile X syndrome (FXS) will require outcome measures capable of assessing short-term changes in cognitive functioning. Potentially useful measures for FXS were evaluated here in a test-retest setting in males and females with FXS (N = 46). Good reproducibility, determined by an interclass correlation (ICC) or weighted kappa (kappa) of 0.