Ovid: Kaplan & Sadock's Comprehensive Textbook of Psychiatry Page 1 of 7

Editors: Sadock, Benjamin J.; Sadock, Virginia A.; Ruiz, Pedro

Title: Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 9th Edition

Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Volume II > 32 - Child Psychiatry > 32.1 - Introduction and Overview

32.1
Introduction and Overview

Caroly S. Pataki M.D.

Evidence Base for Identifying and Treating Childhood Psychiatric

Disorders
Over the last decade the field of child and adolescent psychiatry has demonstrated significant growth in
knowledge of the scientific bases of neuropsychiatric disorders, as well as in the development of
evidence-based psychosocial and psychopharmacologic treatments for these disorders in childhood.
Highlights of many scientific advances pertaining to child and adolescent psychiatry are discussed in this
child psychiatry chapter and include these important areas of investigation. Genetic research, including
genome-wide linkage scans seeking to identify gene loci, have focused on several childhood disorders,
including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), Tourette's
syndrome (TS), and obsessive-compulsive disorder (OCD). Pharmacogenomic studies aiming to identify
genes that predict treatment response or adverse effects are emerging in the area of ADHD with some
promising preliminary results. Neuroimaging studies have elucidated the brain development of typically
developing children, as well as in children with psychiatric disorders. For example, neuroimaging studies
have revealed that whereas total brain volume remains virtually stable after the age of 5 years, there are
two dynamic processessynaptic pruning and myelinationthat continue through adolescence and early
adulthood and profoundly influence cognitive and social decision making and behavior. Furthermore,
neuroimaging studies have led to the conclusion that girls and boys differ in the timing of maximal gray
matter volume and its normal decline after puberty, in that the process occurs about 1 year earlier in
boys than in girls. A variety of neuroimaging techniques, such as magnetic resonance imaging (MRI),
functional MRI, diffusion tensor imaging (DTI), computerized tomography (CT), single photon emission
computerized tomography (SPECT), and positron emission tomography (PET) have been increasingly
employed to uncover both morphology and function of various parts of the brain to further understand
childhood psychiatric disorders such as ADHD, mood disorders, OCD, and anxiety disorders, including
posttraumatic stress disorder (PTSD).

The observed variations in child temperament and personality development have been studied for many
generations, yet accumulating research has identified predictable links between certain temperamental
traits and various psychiatric disorders. Current investigations aimed at further identifying the genetic,
neurobiological, and psychosocial influences on temperament and childhood psychopathology have led to
hypotheses about these relationships, including the following: (1) Temperament and psychopathology
share common etiologic factors, (2) temperament may increase the risk of particular psychopathology,
and (3) temperament and psychopathology are distinct, yet influence each other. These and other
hypotheses about the relationship between temperament and psychiatric disorders continue to be under
investigation. An ever-increasing number of scientifically designed investigations of the safety and
efficacy of psychosocial interventions and psychopharmacological agents for a wide range of child
psychiatric disorders have provided an evidence base for reliable cognitivebehavioral therapies and

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pharmacological modalities as components of treatment for children and adolescents. Large multisite
randomized, placebo-controlled clinical trials (RCTs) and single-site RCTs, most typically investigating
cognitivebehavioral therapies and a variety of psychopharmacologic agents, particularly selective
serotonin reuptake inhibitors (SSRIs) and atypical antipsychotic agents, have provided scientific evidence
for the treatment of multiple childhood psychiatric disorders such as ADHD, major depression, obsessive-
compulsive disorder, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder,
and the pervasive developmental disorders.

Classification of Childhood Psychiatric Disorders

Researchers and clinicians alike depend on a classification system of psychiatric disorders that is both
valid and reliable to maximize clinical investigation and translate the findings into evidence-based
treatment.

The most current version of the Diagnostic and Statistical Manual of Mental Disorders, the text revision of
the fourth edition (DSM-IV-TR), provides a categorical classification that reflects the consensus of current
formulations of psychiatric disorders, with no assumption that each category of disorder is a completely
discrete entity with clear-cut boundaries. Children and adolescents who meet criteria for the same
psychiatric diagnoses may present with heterogeneous clinical pictures. DSM-IV-TR defines a psychiatric
disorder as a clinically significant set of symptoms that is associated with current distress or impairment
in one or more areas of functioning.

The first edition of the World Health Organization's International Statistical Classification of Diseases to
contain a section for mental illness was the sixth (ICD-6). The first formal draft of a U.S. variant of this
document, the DSM, was developed shortly thereafter, in 1952, by the Committee on Nomenclature and
Statistics of the American Psychiatric Association.

Dennis Cantwell, along with multiple colleagues, was instrumental in the field of child and adolescent
psychiatry by suggesting in
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the 1970s revisions to the DSM classification system in an effort to facilitate empirical investigation of
child and adolescent psychiatric disorders. These efforts were first realized in the development of the
DSM-III in 1980. The DSM-III included such methodological innovations as a requirement for explicit
diagnostic criteria for each disorder, use of the multiaxial system, and a diagnostic focus on
phenomenology rather than etiology.

Although both categorical and dimensional approaches have merit in describing psychiatric syndromes in
childhood and adolescence, the DSM uses only categorical criteria to identify psychiatric disorders. The
overlap of behavioral and mood symptoms across multiple childhood and adolescent disorders made
defining the boundary between one disorder and another challenging. In addition, it soon became evident
that within more severely psychiatrically impaired child and adolescent populations, comorbidity is the
rule rather than the exception.

Developmental Perspective: Identifying the Emergence of a

Childhood Psychiatric Disorder

Onset
Onset of a psychiatric disorder is a challenging concept in child and adolescent psychiatry because it is
often difficult to pinpoint reliable landmarks for sufficient symptoms and impairment. Defining the onset
of a disorder by a single impairing symptom might lead to the inclusion of a heterogeneous group of

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disorders, whereas inclusion of only a rigid set of symptoms might exclude important subtypes. Age at
onset of a childhood or adolescent psychiatric disorder is a variable of considerable importance because
the emergence of a known constellation of symptoms at a younger-than-expected age might reflect
increased vulnerability genetically or environmentally. For example, an earlier-than-expected age of
onset of major depressive disorders has been associated with an increased probability of depressive
disorders in first-degree relatives and implies an increased genetic vulnerability.

Delayed Onset
The investigation of age at onset of a psychiatric disorder can be applied to models of delayed onset of
illnesses. For example, degeneration is a model of delayed onset of disease that characterizes conditions
such as Alzheimer's disease and Parkinson's diseasethat is, gradual loss of target neurons over time
results in a predictable behavioral and neurological deficit. Developmental failure (i.e., a lack of
physiological development within the nervous system at the appropriate time) is another model of
delayed onset of a disease process.

A theory of delayed onset of a disorder, the two-hit model, hypothesizes that the emergence of a disorder
is related to a primary genetic vulnerability triggered by exposure to a second event that may be
environmental. For example, the rate of emergence of bipolar disorders increases markedly during
adolescence, is maximal in young adulthood, and then gradually diminishes. One model to explain the
emergence of a disorder with this distribution is a genetic predisposition (first hit) leading to vulnerability
for the disorder and a second exposure, possibly the process of puberty itself or an adverse life event
(second hit), that results in the emergence of the disorder.

Genetic anticipation is defined as the emergence of more severe forms of a genetic disorder in successive
generations. This mechanism has been shown to contribute to the severity of pathology in a number of
genetic disorders that are caused by mutations of DNA triplet repeat nucleotide sequences. Increases in
repeat patterns of three nucleotides, (e.g., GACGACGAC) increase the length of DNA sequences and result
in pathological genes. Triplet repeat expansion has been shown to be the mechanism of a number of
genetic disorders, including Huntington's disease and fragile X syndrome. Anticipation has been suggested
as a possible explanation for increasingly severe psychopathology in successive generations in psychiatric
disorders. The investigation of possible molecular bases of anticipation in psychiatric disorders, such as
the increased density of genetic triplet repeat expansions shown in Huntington's disease and fragile X
mental retardation, is on the horizon.

Past Evidence from Neuroimaging Studies

Child and adolescent brains have been described by clinicians and researchers as works in progress,
with a series of predictable pattern of biological processes that extend into and beyond adolescence. The
neuroimaging work of Giedd, Rappoport, Rosenberg, Castellanos, and many others over the last decade
has revealed the typical wave of high production of gray matter among developmentally normal
adolescents emerging just before puberty. Furthermore, investigations have documented the links
between the pruning and myelination processes in various sites in the brain and the subtle increases in
social and emotional problem-solving abilities that typically emerge in later adolescence. Other
investigations have identified areas of the brain targeted in children who learn first and second languages
early in life. Functional MRI scans have determined the spatial relationship of language centers in children
who have first and second languages. In such children both language centers appear in the same cortical
region, whereas, when a second language is acquired in adult life, the new language center is not
represented in the same cortical region as the first language. MRI studies have also provided evidence that
adolescents process emotional stimuli differently than adults. Using functional MRI and presenting

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pictures of faces depicting various emotions, Yurgelun-Todd and colleagues showed that in young teens,
who typically have difficulties with the task, the amygdala (a brain center for fear reactions) is activated
during the task of identifying the emotions presented, whereas in older teens, who perform better on the
task, the frontal lobes are more active in the process of identifying emotions in the stimuli. There were
also additional findings indicating that language tasks correlated with activation of temporal lobes in
young teens and of frontal lobes in older teens. These changes in brain activation are also correlated with
structural changes known to occur in the temporal lobe white matter.

Advances in neuroscience, genetic research, and neuroimaging techniques have opened up doors within
child and adolescent psychiatry to the understanding of developmental changes as children grow and
develop, as well as in single-gene disorders, such as fragile X syndrome and more complex
neuropsychiatric phenotypes.

The foregoing body of neuroimaging work has led the way for investigators to use these techniques to
study childhood-onset psychiatric disorders using biomarkers as potential diagnostic indicators, as well as
for tracking their changes after efficacious treatments have been administered.

Risk and Protective Factors

Risk factors include all variables that increase the probability that a given child or adolescent will develop
psychopathology. Protective factors decrease the risk of developing psychopathology. Demographics,
psychosocial factors, biological factors, genetics, family environment, and external environment interact
to produce risk and protection from psychiatric disorders. Rarely can a single risk factor account for the
entire variance between the emergence and inhibition
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of a psychiatric disorder. Thus, the study of psychiatric risk is complicated and multifactorial. Risk factors
often studied for influence on the emergence of psychiatric disorders among children and adolescents
include family history of psychiatric disorders, social class, intellectual function, adverse life events,
temperamental factors, and the quality of family and peer relationships. Developmental delays, child
maltreatment, and high levels of family conflict increase the risk of psychiatric disorder. Protective
factors that have been identified and studied include individual temperamental predisposition, positive
family relationship, and other attributes of the external environment.

Types of Interventions
Interventions that can be investigated for efficacy include clinical interventions, targeted interventions,
and universal interventions. Intervention studies are an important outcome component of an empirical
model of study within child and adolescent psychiatry.

Clinical interventions are those in which a family with a child or adolescent who has been identified as
having a psychiatric problem seeks treatment. Psychosocial, psychopharmacological, and other
environmental interventions can be compared with a placebo condition and with each other. Such efficacy
studies are necessary to substantiate the benefit of the treatments. Because close to one half of families
who begin psychiatric treatment terminate prematurely, the nature and delivery of the treatments also
merit investigation.

Targeted interventions are those designed for children who have been identified as having an increased
risk of a psychiatric disorder but whose families are not seeking treatment. Children can be identified
either by an external factor, such as a family characteristic (e.g., drug-addicted parent, family receiving
state assistance), or through a behavior (e.g., defiance or aggression in the classroom). Thus, a child can
be monitored or receive some psychosocial intervention on the basis of the risk factorin some cases,

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correlated with an already existing psychiatric disorder and, in other cases, pre-empting the emergence
of a psychiatric disorder. The difficulty with these interventions is that the families may not want the
intervention or the threshold for identification is not correlated with a clinically relevant behavior.

Universal interventions are received by all children and families within a particular geographical
distribution. They may occur throughout a targeted school or community or on a citywide, statewide, or
national basis. This prevention strategy, also termed primary prevention, obviously reaches more children
than any other method of intervention, but questions arise about the benefit and need of the intervention
for the population at large, as well as the costbenefit ratio.

Study of the risk factors and protective factors is leading the field to develop the most effective
combination of prevention strategies for children and adolescents. Randomized clinical trial investigations
of interventions for child and adolescent psychiatric disorders are accelerating in frequency, and evidence
is increasingly guiding clinical strategies in the treatment of childhood psychiatric disorders. The goals for
the field of child and adolescent psychiatry are to diminish risk factors, enhance protective factors,
prevent the emergence of psychiatric disorders, and, when prevention is not possible, to provide
efficacious treatments.

Suggested Cross-References
In-depth reviews of the following areas of child and adolescent psychiatry can be found in Chapters 32,
33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 and 49. Chapter 32 details normal child and
adolescent development; Chapter 33 discusses the psychiatric examination of the infant, child, and
adolescent. Chapter 34 covers mental retardation; Chapters 35, 36 and 37 detail learning disorders, motor
skills disorders, and communication disorders. Chapter 38 reviews the pervasive developmental disorders;
Chapter 39, the attention-deficit disorders; and Chapter 40, the disruptive behavior disorders. Chapter 41
covers feeding and eating disorders of infancy and early childhood. Chapter 42 covers tic disorders;
Chapter 43 discusses elimination disorders; and Chapter 44 details stereotypic movement disorders and
other disorders of infancy, childhood, and adolescence and reactive attachment disorder of infancy or
early childhood. Chapter 45 discusses mood disorders; Chapter 46 reviews anxiety disorders of childhood,
including separation anxiety disorder, obsessive-compulsive disorder, and selective mutism. Chapter 47
discusses schizophrenia with childhood onset. Chapter 48 details psychiatric therapies, including
individual psychotherapy, short-term psychotherapy, cognitive and behavioral therapies, group
psychotherapy, pharmacotherapy, residential and inpatient treatment, community-based treatments,
partial hospital and ambulatory services, and psychiatric treatment of adolescents. Chapter 49 includes
special areas of interest within child and adolescent psychiatry, including psychiatric aspects of day care;
adoption; foster care; physical abuse, sexual abuse, and neglect of children; children's reaction to illness,
hospitalization, and surgery; psychiatric sequelae of human immunodeficiency virus infection and
acquired immune deficiency syndrome; childhood or antisocial behavior; borderline intellectual function
and academic problems; dissociative disorders; posttraumatic stress disorder; gender identity and sexual
issues; identity problem and borderline disorders; adolescent substance abuse; forensic child psychiatry;
ethical issues in child psychiatry; school consultation; and psychiatric prevention in children.

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