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Chapter 52. Neurobiology of Childhood Disorders

Daniel S. Pine, M.D.
DOI: 10.1176/appi.books.9781585623860.433538

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Mental health sciences witnessed a paradigm shift in the late twentieth century through the influence of three research themes. First, a focus on biology emerged following changes in psychiatric nomenclature and psychopharmacology. Second, advances in neuroscience provided heretofore unseen insights on the relationship between neural and information-processing functions, paving the way for a clinical neuroscience approach to mental illness. Third, the school of developmental psychopathology emerged, based on the recognition that most chronic mental illnesses have their roots in childhood. The current chapter, which focuses on the biology of childhood mental disorders, integrates these three themes. Given the breadth of work in each area, let alone the combination of the three, this chapter cannot provide a comprehensive review. Rather, I summarize major themes while providing illustrative examples from research on specific disorders.

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FIGURE 52–1. A conceptual framework for biological research.This figure illustrates a framework in which to place current research on the biology of pediatric mental syndromes. The framework attempts to link understandings of brain function to clinical categorization by examining the relationship between variations in brain function and specific information-processing functions. ADHD = attention-deficit/hyperactivity disorder; DBDs = disruptive behavior disorders; PDDs = pervasive developmental disorders.

FIGURE 52–2. Response reversal and the medial prefrontal cortex.This figure shows details of a probabilistic response reversal task (A). In this task, subjects begin by trying to select a rewarded target (e.g., the giraffe) while avoiding a punished target (e.g., the elephant). Following acquisition of this "giraffe-reward" rule, the contingencies change in the reversal phase of the task. Functional magnetic resonance imaging (B) demonstrates that during this learning-related process, decreased engagement of the medial prefrontal cortex (PFC) occurs in trials when adult subjects commit errors by failing to learn the new "elephant-reward" rule. Deficient medial PFC engagement on such tasks in some pediatric mental syndromes might reflect a role for perturbed medial PFC function in the condition. BOLD = blood oxygenation level–dependent.Source. (A) Reprinted from Finger EC, Marsh AA, Mitchell DG, et al: "Abnormal Ventromedial Prefrontal Cortex Function in Children With Psychopathic Traits During Reversal Learning." Archives of General Psychiatry 65:586–594, 2008. Copyright 2008, American Medical Association. Used with permission.(B) Reprinted from Budhani S, Marsh AA, Pine DS, et al: "Neural Correlates of Response Reversal: Considering Acquisition." Neuroimage 34:1754–1765, 2007. Copyright 2007, Elsevier. Used with permission.

FIGURE 52–3. Changes in cerebral cortex in childhood-onset schizophrenia.Serial acquisition of structural magnetic resonance imaging data was used to map portions of the cerebral cortex (shown in scatterplots on the right side of the figure) where patients with childhood-onset schizophrenia (COS) {} show distinct changes in brain structure relative to healthy peers (control subjects) {}. Part A shows normalization in posterior regions in COS patients; part B shows divergence from control subjects in anterior regions.*A false discovery rate procedure was used to determine the threshold for significance at t = 2. No covariates were included in the model.Source. Reprinted from Greenstein D, Lerch J, Shaw P, et al.: "Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults." Journal of Child Psychology and Psychiatry 47:1003–1012, 2006. Copyright 2006, Wiley-Blackwell. Used with permission.

FIGURE 52–4. Event-related potentials in pediatric bipolar disorder.This figure shows P3 event-related potential (ERP) amplitude at the parietal Pz site during performance of a frustrating task. The task, which requires subjects to quickly identify a target, is made quite difficult, leading to frustration through frequent incorrect responses (A). As shown in B, when patients with bipolar disorder (n = 35; blue) make errors, ERP amplitude, phase-locked to these errors, is significantly lower than in both healthy peers (n = 26; red) (P <0.01) and peers with severe mood dysregulation but without bipolar disorder (n = 21; green) (P <0.05).Source.Rich et al. 2007.

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