Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain

Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions between two commonly prescribed psychotropic medications with sterol inhibiting side effects, trazodone (TRZ), an antidepressant, and aripiprazole (ARI), an antipsychotic. In vitro cell culture experiments revealed that both medications alone disrupted neuronal and astroglial sterol biosynthesis in dose-dependent manners. Furthermore, when ARI and TRZ were combined, exposure resulted in an additive 7-dehydrocholesterol (7-DHC) increase, as well as desmosterol (DES) and cholesterol decreases in both cell types. In adult mice, at baseline, we found that the three investigated sterols showed significant differences in distribution across the eight assessed brain regions. Furthermore, experimental mice treated with ARI or TRZ, or a combination of both medications for 8 days, showed strong sterol disruption across all brain regions. We show ARI or TRZ alone elevated 7-DHC and decreased DES levels in all brain regions, but with regional differences. However, the combined utilization of these two medications for 8 days did not lead to additive changes in sterol disturbances. Based on the complex roles of 7-DHC derived oxysterols, we conclude that individual and potentially simultaneous use of medications with sterol biosynthesis-inhibiting properties might have undesired side effects on the adult brain, with as yet unknown long-term consequences on mental or physical health.     

Genetic evidence for asymmetric hybridization between menhadens (Brevoortia spp.) from peninsular Florida

Hybridization between the North American menhadens Brevoortia smithi , Brevoortia tyrannus and Brevoortia patronus has been reported by numerous authors, based primarily on the morphological intermediacy of hybrids relative to each parental type. In this study, genetic characterization of individuals in areas previously designated as hybrid zones validates the presence of F₁ hybrids. Evidence from microsatellite genotypes indicates that B. patronus and B. smithi are parental species of hybrids on both sides of the Florida peninsula, and mitochondrial DNA (mtDNA) haplotypes suggest a maternal contribution by B. smithi in each case. Hybrids between B. tyrannus and B. smithi were not identified in this study. The presence of B. patronus on the Atlantic coast of Florida, coupled with admixture between this species and B. tyrannus , has likely influenced the mixed lineage assortment of mtDNA haplotypes demonstrated in this study and in previous studies.     

Reduced Visual Cortex Gray Matter Volume and Thickness in Young Adults Who Witnessed Domestic Violence during Childhood

Exposure to interparental violence is associated with negative outcomes, such as depression, post-traumatic stress disorder and reduced cognitive abilities. However, little is known about the potential effects of witnessing domestic violence during childhood on gray matter volume (GMV) or cortical thickness. High-resolution 3.0 T volumetric scans (Siemens Trio Scanner) were obtained on 52 subjects (18–25 years) including 22 (6 males/16 females) with a history of visually witnessing episodes of domestic violence, and 30 (8 males/22 females) unexposed control subjects, with neither a current nor past DSM-IV Axis I or II disorder. Potential confounding effects of age, gender, level of parental verbal aggression, parental education, financial stress, full scale IQ, and total GMV, or average thickness were modeled using voxel based morphometry and FreeSurfer. Witnessing domestic violence subjects had a 6.1% GMV reduction in the right lingual gyrus (BA18) (P = 0.029, False Discovery Rate corrected peak level). Thickness in this region was also reduced, as was thickness in V2 bilaterally and left occipital pole. Theses regions were maximally sensitive to exposure to witnessing domestic violence between 11–13 years of age. Regional reductions in GMV and thickness were observed in both susceptible and resilient witnessing domestic violence subjects. Results in subjects witnessing domestic violence were similar to previously reported results in subjects with childhood sexual abuse, as the primary region affected was visual cortex. Brain regions that process and convey the adverse sensory input of the abuse may be specifically modified by this experience, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. These findings fit with preclinical studies showing that visual cortex is a highly plastic structure.     

A sex-specific test of selection in utero

We find support for the hypothesis that changes in the monthly odds of a twin among live-born males predict subsequent and opposite changes in the odds of a twin among live-born females. The hypothesis arises from the long standing argument that natural selection has conserved mechanisms by which pregnant women in stressed populations spontaneously abort fetuses least likely to yield grandchildren. Previous attempts to empirically test this argument focus almost entirely on males. We contribute to the literature by showing that, consistent with the logic of natural selection, maternal adaptations to environmental changes likely have effects on the survival of both male and female conceptuses and fetuses.     

Agar Diffusion Method for Negative Staining of Microbial Suspensions in Salt Solutions

Microbial suspensions in a saline medium can be prepared for negative staining by a simple agar diffusion method that achieves a high degree of particle concentration.     

Partial proteolytic protein maps: Cleveland revisited

Low concentrations of sodium dodecyl sulfate have a dramatic effect on the partial proteolytic products obtained by digesting bovine serum albumin with chymotrypsin or trypsin. The effect observed may be important for the interpretation of peptide maps obtained by the method of D. W. Cleveland et al. [(1977) J. Biol. Chem. 252, 1102-1106].