in the same chromosomal region. Although the locus of the mutation is the same, its effects on the behavioral phenotype of the child differ depending on which parent is the origin of the mutation (Goldstone, 2004; Lalande and Calciano, 2007; Nicholls and Knepper, 2001).

Another example of the importance of epigenetic influences in the cause of a disorder is Rett syndrome, a progressive neurodevelopmental disorder characterized by motor, speech, and social behavioral abnormalities (Chahrour and Zoghbi, 2007). Mutations in the MeCP2 gene cause Rett syndrome and, less commonly, other neurodevelopmental disorders, including classic autism, mental retardation, early-onset bipolar disorder, and early-onset schizophrenia. This gene encodes a protein that epigenetically alters the expression of other genes (Chahrour and Zoghbi, 2007; Zlatanova, 2005). In other words, this specific genetic mutation causes disease through epigenetic mechanisms, underscoring how complex, intimate, and interactive genetic and epigenetic factors are in influencing the development of disorders.

Epigenetic modifications of the genome are also necessary for various learning and memory processes in the brain (Levenson and Sweatt, 2005, 2006; Levenson, Roth, et al., 2006; Reul and Chandramohan, 2007; Fischer, Sananbenesi, et al., 2007), suggesting that these processes may be important in the etiology of various mental retardation syndromes. Epigenetic influences play a prominent role as well in changes in the brain and in behavior related to establishing preferences for drugs of abuse in animal models of addiction (Kumar, Choi, et al., 2005). Finally, epigenetic modifications of the genome have been shown to be necessary to produce the behavioral response to antidepressant medications in a mouse model of depression (Newton and Duman, 2006; Tsankova, Berton, et al., 2006).

BRAIN DEVELOPMENT

MEB disorders in children involve disturbances in the most complex, highly integrated functions of the human brain. Understanding from a biological perspective how these functional capacities develop and how they are disrupted is an immense challenge. This section offers a brief overview of current knowledge about the complex processes that contribute to the normal development of the human brain, along with examples of their relationship to the causes of MEB disorders.

Sources of Knowledge of Human Brain Development

Knowledge of normal human brain development and of the abnormalities that produce disorders is limited by the difficulty of studying the human brain at the level of molecules and cells. The human data on brain



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