DNA methylation, the early-life social environment and behavioral disorders

One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed

Evolution of Shapes in 59Cu

High-spin states in Cu-59 were populated using the fusion-evaporation reaction Si-28 + Ca-40 at a beam energy of 122 MeV. The Gammasphere Ge-detector array in conjunction with the 4pi charged-particle detector array Microball allowed for the detection of gamma-rays in coincidence with evaporated light particles. The resulting extensive high-spin decay scheme of Cu-59 is presented, which comprises more than 320 gamma-ray transitions connecting about 150 excited states. Their spins and parities have been assigned via directional correlations of gamma-rays emitted from oriented states. Average quadrupole moments of rotational bands have been determined from the analysis of residual Doppler shifts. Shell model calculations in the fp shell are invoked to study some of the low-spin states, while the experimental characteristics of the rotational bands are analyzed in the configuration-dependent cranked Nilsson-Strutinsky (CNS) approach

Doorway States in the Gamma Decay-out of the Yrast Superdeformed Band in 59Cu

The decay-out process of the yrast superdeformed band in Cu-59 has been investigated. The firm determination of spin, parity, excitation energy, and configuration of the states involved in this process constitutes a unique situation for a detailed understanding of the decay-out mechanism. A theoretical model is introduced that includes a residual interaction and tunneling matrix element between bands, calculated in the configuration-dependent cranked Nilsson-Strutinsky model. This interaction causes the decay to occur via a small number of observed doorway states

Tardive Dyskinesia: Outcome of Antipsychotic Treatment and Brain Damage?

Tardive dyskinesia (TD), marked by abnormal involuntary movements and frequently expressed as perioral activity, represents an adverse outcome of prolonged antipsychotic therapy, occurring in approximately 5 % of patients per treatment year. Although neuronal mechanisms underlying TD are largely unknown, more recent experimental studies in animal models of TD are providing insight into the neuronal mechanisms associated with TD and implicating newer treatment approaches. It is now evident that a predominance in the ratio of dopamine (DA) D1:D2 receptor (R) activation accounts for induction of perioral movements in rodent models of TD, in nonhuman primate models of TD, and in humans with TD. Experimentally, TD is produced in animal models of TD, in a manner analogous to that by which TD is produced in humans - by continuous and prolonged administration of a DA D2R antagonist (i.e., an antipsychotic drug). More recently, in a rodent model of TD, it has been shown that a lesion of dopaminergic - mainly nigroneostriatal - neurons reduces the time latency for occurrence of TD, also increases the severity of perioral activity, and results in permanence of TD after complete removal of D2R antagonist treatment. The induction of perioral activity is related to DAR supersensitivity but unrelated to numbers of D2R and D2R in the neostriatum, a brain region associated with perioral activity. More apropos, serotoninergic systems are now recognized as having a greater role in effecting perioral activity, and it appears that 5-HT2C receptor antagonists are most effective in abating perioral activity in a rodent model of TD. These processes and mechanisms, topics addressed in this chapter, highlight a newer understanding of mechanisms underlying TD and provide insight into new approaches towards treatment of TD in humans