Anxiety Disorders of Infancy, Childhood, and Adolescence
46.1 Obsessive-Compulsive Disorder of Infancy, Childhood, and Adolescence
Obsessive-compulsive disorder (OCD) is characterized by the presence of recurrent intrusive thoughts associated with anxiety or tension and/or repetitive purposeful mental or physical actions aimed at reducing fears and tensions caused by obsessions. It has become increasingly evident that the majority of cases of OCD begin in childhood or adolescence. The clinical presentation of OCD in childhood and adolescence is similar to that in adults, and the only alteration in diagnostic criteria in the text revision of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for children is that they do not necessarily demonstrate awareness that their thoughts or behaviors are unreasonable. Pediatric OCD has been investigated with respect to treatment with placebo-controlled trials of pharmacologic agents and cognitive-behavioral therapy (CBT); it is the only childhood anxiety disorder with data showing optimal treatment to include a combination of serotoninergic agents and CBT treatment.
EPIDEMIOLOGY
Obsessive-compulsive disorder is common among children and adolescents, with a point prevalence of about 0.5 percent and a lifetime rate of 1 to 3 percent. The rate of OCD rises exponentially with increasing age among youth, with a rate of 0.3 percent in children between the ages of 5 years and 7 years and rising to 0.6 percent among teens. Rates of OCD among adolescents are greater than rates for disorders such as schizophrenia and bipolar disorder. Among young children with OCD there appears to be a slight male predominance, which diminishes with age.
ETIOLOGY
Genetic Factors
OCD is a heterogeneous disorder that has been recognized for decades to run in families. Family studies have documented an increased risk of at least fourfold in first-degree relatives of individuals with early-onset OCD. In addition, the presence of subclinical symptom constellations in family members appears to breed true. Molecular genetic studies have suggested linkage to regions of chromosomes 2 and 9 in certain pedigrees with multiple members exhibiting early-onset OCD. Candidate gene studies have been inconclusive. Family studies have pointed to a relationship between OCD and tic disorders such as Tourette’s syndrome. OCD and tic disorders are believed to share susceptibility factors along with the concept of a broader “obsessive-compulsive spectrum” including eating disorders, and somatoform disorders may account for expression of repetitive and stereotyped symptoms.
Neuroimmunology
The association of emergence of OCD syndromes following a documented exposure to or infection with group A β-hemolytic streptococcus in a subgroup of children and adolescents has led to the studies of immune responses in OCD. Cases of infection-triggered OCD have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococcus and are believed to represent an autoimmune process such as that of Sydenham’s chorea during rheumatic fever. It is hypothesized that exposure to streptococcal bacteria activates the immune system, leading to inflammation of the basal ganglia and resulting in disruption of the cortical-striatal-thalamo-cortical function. Magnetic resonance imaging (MRI) has documented a proportional relationship between the size of the basal ganglia and the severity of OCD symptoms. The presentation of OCD in children and adolescents due to acute exposure to group A β-hemolytic streptococcus represents a minority of OCD cases in this population.
Neurochemistry
Involvement of several neurotransmitter systems, including the serotonin system and the dopamine system, have been postulated to contribute to the emergence of OCD. The observation that serotonin reuptake inhibitors (SSRIs) diminish symptoms of OCD, along with the findings of altered sensitivity to the acute administration of 5-hydroxytryptamine agonists, supports the likelihood that the serotonin system plays a role in OCD. In addition, the dopamine system is believed to be influential in this disorder, especially in light of the frequent comorbidity of OCD with tic disorders in children. Clinical observations have indicated that obsessions and compulsions may be exacerbated during treatment of ADHD (another frequent comorbidity) with stimulant agents. Dopamine antagonists administered along with SSRIs may augment the effectiveness of SSRIs in the treatment of OCD. It is most likely that multiple neurotransmitter systems play a role in OCD.
Neuroimaging
Both computed tomography and MRI of untreated children and adults with OCD have revealed smaller volumes of basal ganglia segments
compared to normal controls. In children, there is a suggestion that thalamic volume is increased. Adult studies have provided evidence of hypermetabolism of frontal cortical-striatal-thalamo-cortical networks in untreated individuals with OCD. Of interest, imaging studies before and after treatment have revealed that both medication and behavioral interventions lead to a reduction of orbit frontal and caudate metabolic rates in children and adults with OCD.
compared to normal controls. In children, there is a suggestion that thalamic volume is increased. Adult studies have provided evidence of hypermetabolism of frontal cortical-striatal-thalamo-cortical networks in untreated individuals with OCD. Of interest, imaging studies before and after treatment have revealed that both medication and behavioral interventions lead to a reduction of orbit frontal and caudate metabolic rates in children and adults with OCD.
DIAGNOSIS AND CLINICAL FEATURES
The most commonly reported obsessions in children and adolescents include extreme fears of contamination—exposure to dirt, germs, or disease—followed by worries related to harm befalling themselves or family members and fear of harming others due to losing control over aggressive impulses. Also commonly reported are obsessional need for symmetry or exactness, hoarding, and excessive religious or moral concerns. Typical compulsive rituals among children and adolescents involve cleaning, checking, counting, repeating behaviors, and arranging items. Associated features in children and adolescents with OCD include avoidance, indecision, doubt, and a slowness to complete tasks. In most cases of OCD among youth, obsessions and compulsions are present. According to DSM-IV-TR, diagnosis of OCD is identical to that of adults, with the modification that, unlike adults, children are not required to recognize that their obsessions or compulsions are excessive or irrational. Table 46.1-1 gives the DSM-IV-TR diagnostic criteria for OCD.
The majority of children who develop OCD have an insidious presentation and may hide their symptoms when possible, whereas a minority of children, particularly boys with early onset, may have a rapid unfolding of multiple symptoms within a few months. OCD is commonly found to be comorbid with other psychiatric disorders, especially other anxiety disorders. There are also higher than expected rates of ADHD and tic disorders, including Tourette’s syndrome, among children and adolescents with OCD. Children with comorbid OCD and tic disorders are more likely to exhibit counting, arranging, or ordering compulsions and less likely to manifest excessive washing and cleaning compulsions. The high comorbidity of OCD, Tourette’s syndrome, and ADHD has led investigators to postulate a common genetic vulnerability to all three of these disorders. It is important to search for comorbidity in children and adolescents with OCD so that optimal treatments can be administered.
Pathology and Laboratory Examination
No specific laboratory measures are useful in the diagnosis of obsessive-compulsive disorder.
When the onset of obsessions or compulsions is believed to be associated with an exposure to or recent infection with group A β-hemolytic streptococcus, antigens and antibodies to the bacteria can be obtained, although a diagnosis of OCD can not be confirmed on the basis of positive results.
Table 46.1-1 DSM-IV-TR Diagnostic Criteria for Obsessive-Compulsive Disorder | ||||||||||||||||||||||||||||||||||||||||||||||||
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DIFFERENTIAL DIAGNOSIS
Developmentally appropriate rituals in the play and behavior of young children must be differentiated from obsessive-compulsive disorder in that age group. Preschoolers often engage in ritualistic play and request a predictable routine, such as bathing, reading stories, or selecting the same stuffed animal at bedtime, to promote a sense of security and comfort. These routines allay developmentally normal fears and lead to reasonable completion of daily activities, in contrast to obsessions or compulsions, which are driven by extreme fears and interfere with normative daily function due to the excessive time that they consume and the extreme distress they cause when not fully completed. The rituals of preschoolers generally become less rigid by the time they enter grade school, and school-aged children usually do not have a surge of anxiety when they encounter small changes in their routine.
Children and adolescents with anxiety disorders such as generalized anxiety disorder, separation anxiety disorder, or social phobia experience more intense worries than children without any anxiety disorders and may express their concerns repeatedly, but these are differentiated from typical obsessions by their more mundane content, whereas obsessions are so excessive that they approach seeming bizarre. A child with generalized anxiety disorder might worry repeatedly about performance on academic examinations, whereas a child with OCD is likely to have intrusive concerns that he or she may lose control and harm a loved one. The compulsions of OCD are not exhibited in other anxiety disorders, but children and adolescents with pervasive developmental disorders often display repetitive behaviors that resemble those of OCD. In contrast to the rituals of OCD, however, children with pervasive developmental disorder are not responding to anxiety, but are more often manifesting stereotyped behaviors that are self-stimulating or self-comforting.
Children and adolescents with tic disorders such as Tourette’s syndrome may exhibit complex repetitive compulsive behaviors that are similar to the compulsions seen in OCD. In fact, children and adolescents with tic disorders are at higher risk for the development of concurrent OCD.
In severe cases of OCD, it may be difficult to differentiate whether psychosis is present, given the extreme and bizarre nature that obsessions and compulsions can possess. In adults and often in children and adolescents with OCD, despite the inability to control the obsessions or the irresistible drive to complete the compulsions, insight about their lack of reasonableness is preserved. When insight is present and underlying anxiety can be described even in the face of significant dysfunction due to bizarre obsessions and compulsion, the diagnosis of OCD is suspect.
COURSE AND PROGNOSIS
OCD with an onset in childhood and adolescence is characterized as a chronic, though waxing and waning, disorder with a great variation in severity and outcome. Follow-up studies suggest that up to 50 percent of affected children and adolescents experience recovery from OCD with minimal remaining symptoms. In a recent study of childhood OCD, treatment with sertraline resulted in close to 50 percent of subjects experiencing complete remission and another 25 percent experiencing partial remission with a follow-up time of 1 year. The predictor of the best outcome was the absence of comorbid disorders, including tic disorders and ADHD. Overall, the prognosis is hopeful for most children and adolescents with mild to moderate OCD. In a minority of cases, however, the OCD diagnosis may be considered a prodrome of a psychotic disorder, which has been found to emerge in up to 10 percent in some samples of children and adolescents with OCD. In children with subthreshold symptoms of OCD, there is a high risk of the development of the full OCD disorder within 2 years. In the majority of studies of childhood OCD, treatment results in improvement if not complete remission in the majority of cases.
TREATMENT
Results from multiple randomized, placebo-controlled trials of both medication and cognitive-behavioral interventions in children and adolescents with OCD show the most successful treatment of this disorder compared to any of the other anxiety disorders of childhood. In a recent multisite National Institute of Health-funded investigation of sertraline and cognitive-behavioral therapy each alone and in combination for the treatment of childhood onset OCD, the Pediatric OCD Treatment Study revealed that the combination was superior to either treatment alone.
Three SSRIs—sertraline (at least 6 years of age), fluoxetine (at least 7 years of age), and fluvoxamine (at least 8 years of age)—have received U.S. Federal Drug Administration approval for the treatment of OCD. The black-box warning for antidepressants used in children for any disorder, including OCD, is applicable, so that close monitoring for suicidal ideation or behavior is mandated when these agents are used in the treatment of childhood OCD.
Cognitive-behavioral therapy geared toward children of varying ages is based on the principle of developmentally appropriate exposure to the feared stimuli coupled with response prevention, leading to diminishing anxiety over time for exposure to feared situations. CBT manuals have been developed to ensure that developmentally appropriate interventions are made and that comprehensive education is provided to the child and parents.
Most treatment guidelines for children and adolescents with mild to moderate OCD recommend a trial of CBT prior to initiating medication. There is evidence that optimal treatment includes the combination of SSRI medication and CBT. In terms of pharmacological interventions, acute treatment of childhood OCD has been shown to occur within 8 to 12 weeks of treatment. The vast majority of children and adolescents who experienced a remission with acute treatment using SSRIs were still responsive over a period of 1 year. Given the lack of data on discontinuation, recommendations for maintaining medication include stabilization and education about relapse risk, and tapering medication during the summer is likely to be advised to minimize academic compromise in case of relapse. For children and adolescents with more-severe or multiple episodes of significant exacerbation of symptoms, treatment for a longer period of time—greater than 1 year—is recommended.
Augmentation strategies enhancing serotonergic effects, for example, atypical antipsychotics such as risperidone, have demonstrated increased response when partial response has been achieved with SSRI agents.
Overall, efficacy of treatment for children and adolescents with OCD is high with appropriate choice of SSRI agent and CBT therapy.
46.2 Separation Anxiety Disorder, Generalized Anxiety Disorder, and Social Phobia
Anxiety disorders are among the most common disorders in youth, affecting more than 10 percent of children and adolescents at some point in their development. Separation anxiety is a universal human developmental phenomenon emerging in infants less than 1 year of age and marking a child’s awareness of a separation from his or her mother or primary caregiver. Normative separation anxiety peaks between 9 months and 18 months and diminishes by about 2.5 years of age, enabling young children to develop a sense of comfort away from their parents in preschool. Separation anxiety, or stranger anxiety as it has been termed, most likely evolved as a human response that has survival value. The expression of transient separation anxiety is also normal in young children entering school for the first time. Approximately 15 percent of young children display intense and persistent fear, shyness, and social withdrawal when faced with unfamiliar settings and people. Young children with this pattern of behavioral inhibition are at higher risk for the development of separation anxiety disorder, generalized anxiety disorder, and social phobia. Behaviorally inhibited children, as a group, exhibit characteristic physiological traits, including higher-than-average resting heart rates, higher morning cortisol levels than average, and low heart rate variability. Separation anxiety disorder is diagnosed when developmentally inappropriate and excessive anxiety emerges related to separation from the major attachment figure. According to the text revision of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), separation anxiety disorder requires the presence of at least three symptoms related to excessive worry about separation from the major attachment figures. The worries may take the form of refusal to go to school, fears and distress on separation, repeated complaints of such physical symptoms as headaches and stomachaches when separation is anticipated, and nightmares related to separation issues.
Separation anxiety disorder and selective mutism are the two anxiety disorders found in the child and adolescent section of DSM-IV-TR, although childhood onset of all of the anxiety disorders is frequent. Children who exhibit recurrent excessive worries pertaining to their performance in school and social settings and experience at least one physiological symptom, such as restlessness, poor concentration, or irritability related to their fears, may be diagnosed with generalized anxiety disorder. Children with generalized anxiety disorder tend to feel fearful in multiple settings and expect more-negative outcomes when faced with academic or social challenges compared with peers. Children who experience recurrent extreme anxiety and avoid social situations in which they fear scrutiny or humiliation may meet the DSM-IV-TR diagnostic criteria for social phobia, a disorder that also occurs in adolescents and adults. Children with social phobia experience distress and discomfort in the presence of peers as well as adults. Separation anxiety disorder, generalized anxiety, and social phobia in children are often considered together in a differential diagnosis and in developing treatment strategies because they are highly comorbid and have overlapping symptoms. A child with separation anxiety disorder, generalized anxiety disorder, or social phobia has a 60 percent chance of having at least one of the other two disorders as well. Of children with one of the aforementioned anxiety disorders, 30 percent have all three of them. Children and adolescents may also have other anxiety disorders described among the adult disorders of DSM-IV-TR, including specific phobia, panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder.
EPIDEMIOLOGY
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