Preventing Mental, Emotional, and Behavioral Disorders Among Young People Progress and Possibilities (2009) / Chapter Skim
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5 Perspectives from Developmental Neuroscience
5 Perspectives from Developmental Neuroscience
Pages 113-150
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From page 113... ...
This chapter illustrates research advances in the framework of developmental neuroscience, including the anatomical and functional development of the brain, molecular and behavioral genetics, molecular and cellular neurobiology, and systems-level neuroscience, that relate to the prevention of MEB disorders. Perspectives from developmental neuroscience provide a foundation for understanding the development of cognitive abilities, emotions, and behaviors during childhood and adolescence, and they thereby reveal valuable opportunities for novel advances in future prevention research.
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From page 114... ...
Next is an examination of neural systems and their role in complex processes that underlie the cognitive and social competence that is essential to healthy emotional and behavioral development. The third section addresses the relationship between developmental neuroscience and prevention science.
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From page 115... ...
The influences of these gene variants on the structural and functional features of cells, neural circuits, and the behaviors they subserve are correspondingly graded as well. Variations in the genetic sequences that encode proteins are only one level of influence on the expression of those genes in the production of cellular proteins.
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From page 116... ...
This extraordinary degree of spatial and temporal control over gene expression makes animal models invaluable in identifying the molecular processes of normal and pathological brain development. The disadvantage of animal models, however, is the difficulty of representing the complex cognitive, behavioral, and emotional symptoms experienced by humans.
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From page 117... ...
interactions can confer both risk and protective effects on the child relative to the effects of either the genetic or environmental influences in isolation. A number of interactions between specific identified genes and specific environmental risk factors have been demonstrated in MEB disorders ( Rutter, Moffitt, and Caspi, 2006)
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From page 118... ...
. Gene–environment correlations can confound cause and effect and hinder measurement of GxE interactions because a genetically determined behavioral trait can produce a systematic variation in environmental exposure, and that environmental variation can be deemed erroneously to be a cause of a behavioral trait under study (Jaffee and Price, 2007; Lau and Eley, 2008)
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From page 119... ...
For example, abundant naturalistic and experimental evidence in humans and animal models has shown that early experience influences reactivity to stress later in life, even into adulthood, and that epigenetic modification of genes that encode components of the stress response can contribute to these enduring effects (Kaffman and Meaney, 2007; Weaver, 2007)
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. BRAIN DEVELOPMENT MEB disorders in children involve disturbances in the most complex, highly integrated functions of the human brain.
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Despite limited data from human and nonhuman primates, the consistency in findings across species suggests that the general features of brain development in animal models are likely to apply to humans as well. Those findings indicate that the wiring of neural architecture is neither fixed nor static.
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From page 122... ...
122 Developmental Phase Early Early Emerging Prenatal Birth Infancy Childhood Childhood Adolescence Adolescence Adulthood Gestation (weeks) 4 8 12 16 20 24 28 32 Neurulation Neuronal Proliferation Neuronal Differentiation Neuronal Migration Synapse Formation Programmed Cell Death Synaptic Pruning Myelination FIGURE 5-2 Timeline of major events in brain development.
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From page 123... ...
. Various physiological and environmental factors can affect prenatal brain development in ways that are either lethal or seriously debilitating (Detrait, George, et al., 2005; Kibar, Capra, and Gros, 2007)
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. Genetic and environmental influences on neuronal migration can produce even more subtle disturbances in the locations of cells that may not be visible at the gross anatomical level but may nevertheless affect functional circuits.
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. The rate of synapse formation increases rapidly after about weeks 24-28 and peaks, at the rate of almost 40,000 new synapses per second, between 3 and 15 months after birth (in the primary sensory and prefrontal cortices, respectively)
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From page 126... ...
Primates are widely believed to have evolved synaptic pruning as a means for removing synaptic connections that are unused and therefore not needed in the environmental context in which the animal finds itself, while conserving and increasing the efficiency of connections that are useful in that context. Thus, survival of most of the synaptic connections that subserve human behavior is influenced by patterns of neural activity, which in turn are the product of environmental influences and experience (Kandel, Schwartz, and Jessell, 2000)
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From page 127... ...
The survival of cells and synapses requires their ongoing neural activity, suggesting that external stimuli and environmental conditions, including relative deprivation, can have important long-term influences on brain development. These influences have been demonstrated in animal models, from rodents to nonhuman primates (Sanchez, Ladd, and Plotsky, 2001)
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From page 128... ...
Changes in brain structure in response to experience, learning, various physiological processes, and pharmacological or environmental agents are known as neural plasticity. Although the molecular mechanisms underlying neural plasticity are not fully understood, experience is known to induce anatomical changes across all levels of the nervous system, from molecular and cellular processes to entire neural pathways.
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From page 129... ...
. The ongoing capacity for change in the brain underlies potential mechanisms through which brain function can compensate for, or even recover from, a disorder, whether that disorder derives primarily from adverse genetic or environmental influences or a combination of both.
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. These effects of childhood maltreatment in humans are consistent with animal models of child abuse and neglect that
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NEURAL SYSTEMS Developmental processes early in brain development establish fundamental brain structure and circuitry. To achieve the complex functions of the brain, signaling circuits that serve similar functions are grouped and integrated in networks both within the cortex and between the cortex and other regions of the brain.
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From page 132... ...
. Experimental emulation and manipulation of various emotions in animal models have shown that the interactions between the amygdala and the hippocampus are influenced heavily by the actions of various neurotransmitters and hormones that mediate the effects of emotional experience on the recall of arousing, rewarding, and stressful life events (McGaugh, 2004; Roozendaal, Okuda, et al., 2006)
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. Disturbances in the extinction of conditioned fear responses have been postulated in the pathogenesis of a wide range of anxiety disorders.
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. Mammalian animal models of the attachment of an infant to a caregiver, as well as the behavioral and neuroendocrine responses to separation from that caregiver, have revealed physiological mediators of attachment and separation responses that have specific and long-term regulatory effects on the hormonal, physiological, and behavioral reactivity of the infant (Hofer, 1994)
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From page 135... ...
. That the levels of disturbance in social behavioral and emotional regulation are dramatically greater following an earlier disruption of social bonds suggests that attachment to caregivers may be subject to a sensitive period early in postnatal development and that early deprivation may lead to subsequent social and emotional disturbances in a dose-dependent manner (Nelson, Zeanah, et al., 2007; O'Connor, Marvin, et al., 2003; Smyke, Dumitrescu, and Zeanah, 2002)
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From page 136... ...
Distinct neural systems are likely to subserve each of these components. Extensive evidence from human imaging studies suggests that the neural systems responsible for processing social stimuli are based primarily in the superior temporal cortex (Zilbovicius, Meresse, et al., 2006; Zahn, Moll, et al., 2007)
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From page 137... ...
Activation of the ventral prefrontal cortex correlates inversely with activity in the amygdala, suggesting that cognitive reappraisal activates the frontal cortex and that the frontal cortex in turn modulates emotion-processing activity in the amygdala (Ochsner, Bunge, et al., 2002)
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. Cognitive reappraisal already is a prominent component of the cognitivebehavioral therapies commonly used in the treatment of depression and anxiety disorders.
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Indeed, findings from human brain imaging studies have increasingly suggested that many differences previously documented in disorders may not represent a primary dysfunction but compensatory responses to the presence of neural dysfunction elsewhere. For example, although longitudinal studies suggest that most cortical abnormalities in children with ADHD represent a maturational delay, some of the differences compared with healthy control children appear to represent a compensatory response.
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. The differences are thought to have their basis at least in part in differences in brain structure and function, which are determined largely by the effects on brain development of both sex hormones and genes encoded on sex chromosomes (Arnold, 2004; Davies and Wilkinson, 2006; Hines, 2003)
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From page 141... ...
This sex-specific difference in rates of illness reverses following puberty, when the prevalence of disorders is higher in girls. RELEVANCE OF DEVELOPMENTAL NEUROSCIENCE TO PREVENTION Relationship to Prevention Interventions Developmental neuroscience provides a great deal of knowledge that will increasingly support preventive intervention approaches for MEB dis orders.
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. Another area in which research in developmental neuroscience has implications for prevention of MEB disorders is targeting the appropriate individuals for the delivery of interventions.
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The possibility of targeting interventions based on evidence from developmental neuroscience is genuine and valid if the following criteria are met: (1) the evidence for the association between a marker or exposure and a disorder is sufficient to identify children at risk reliably, (2)
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Rich theories of the pathogenesis of MEB disorders in young people can be developed using animal models and other methods of basic science research, as well as neurobiological studies in humans. Accordingly, theories derived from developmental neuroscience should have a prominent role in informing the design of such interventions.
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From page 145... ...
Such a mismatch could conceivably serve as a risk for pathology, adding a level of complexity to the optimal design of preventive interventions despite the best of intentions in the design and implementation of an intervention. While theories from developmental neuroscience can inform prevention approaches, findings from prevention trials that suggest causal mechanisms should generate hypotheses that can be tested and further elaborated by basic and clinical neuroscientists using animal models and other neurosciencebased approaches.
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From page 146... ...
Intervention strategies that modify environment and experience have great potential to promote healthy development of the brain and to prevent MEB disorders. The growth of knowledge in developmental neuroscience has been particularly rapid in the defining of the roles of genetic, epigenetics, and gene–environment interactions on brain development.
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From page 147... ...
Second, advances in understanding and identifying gene–environment interactions have illuminated the ways in which specific genetic variants and life experiences both confer risk for and protect against developing MEB disorders. Third, much has been learned about the mechanisms of epigenetic modification of the genome that can confer enduring changes in gene expression and behavior.
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From page 148... ...
Thus, efforts to understand the neurological basis of cognitive, emotional, and behavioral development, and especially to understand how these neural substrates can be modified through environmental intervention, are clearly an important basis for prevention research. Although research efforts are justified for intervention strategies at all stages of development in young people, developmental neuroscience has provided overwhelming evidence for the particular importance of fetal and early postnatal development for establishing the fundamental anatomical and functional architecture of the human brain that will endure throughout life, as well as evidence for the existence of sensitive periods for environmental influences in infancy.
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Recommendation 5-3: Research funders, led by the National Institutes of Health, should fund research consortia to develop multidisciplinary teams with expertise in developmental neuroscience, developmental psychopathology, and preventive intervention science to foster transla tional research studies leading to more effective prevention efforts. A well-supported collaborative research approach of this kind would provide an opportunity to investigate the potential use of genotyping and other biological markers as a basis for indicated prevention strategies.
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