Lizette Perez Psychiatry Rotation Bipolar Disorder in Children Introduction Due to recent publications, bipolar disorder (BPD) has

been diagnosed with increased frequency in the last ten years, and this increase is the cause of much debate. Bipolar disorder in children is poorly defined and can lead to misdiagnosis and inappropriate treatment. The DSM-IV-TR does not explicitly define BPD in children. Currently, according to the DSM-IV-TR, the diagnostic criteria for a manic episode are the same for children as for adults. However, the classic manic episode described in the DSM-IV-TR is uncommonly seen in children. Instead, atypical manic episodes with no discrete mood cycle are most often observed. The symptoms seen in these atypical manic episodes are extreme mood variability (or lability), intermittent aggressive behavior, high levels of distractibility, poor attention span, and extreme irritability. Also, in adolescents, mania may presents with higher incidence of psychotic features and hospitalization is often necessary. Adolescents may present with delusions and hallucinations and may have grandiose notions about their power, worth, knowledge, family, or relationships. Also they may have persecutory delusions, flight of ideas, and gross impairment of reality testing. Since these aforementioned symptoms do not fully satisfy the diagnostic criterion that has been established by the DSM-IV-TR, this makes the diagnosis and treatment of BPD in children very controversial. Instead of using the BPD label, some psychiatrist (and even the authors of the DSM-V) are leaning towards diagnosing these children with Severe Mood Dysregulation or alternatively, Temper Dysregulation Disorder with Dysphoria (TDD). Epidemiology Bipolar disorder in children and adolescents is rare worldwide. Strong heritability has been shown in twin studies where the concordance rate in monozygotic twins is 0.67-0.85 (3), whereas that of dizygotic twins and siblings is much lower. Childhood-onset BPD is also associated with a family history of BPD, particularly in first-degree relatives. In pre-pubertal children there is 0.2%-0.4% lifetime prevalence and in older adolescents there is a 1% lifetime prevalence (1). The numbers of those diagnosed are higher in the United States and it is believed that the US is the only country where BPD is the diagnosed in pre-school-aged children. This brings about the question about whether the diagnostic practices in the US are different, whether the genetic makeup of the children is different, or whether there is an environmental cause for these higher numbers. Most believe that practitioners in the US use less stringent criteria for diagnosing BPD in children, thus increasing the number of those receiving the diagnosis. On the other side of the argument, according to Sadock, a recent epidemiological survey of current illness in children less than 13 years old found no cases of classic bipolar illness (1). Furthermore, longitudinal studies are needed to determine if children with earlyonset atypical bipolar disorder become adults with bipolar disorder.

Etiology Genetic factors The children of one parent with BPD have a 25% chance of having a mood disorder. The offspring of two parents with BPD have a 50%-75% risk of developing a mood disorder (1). Neurobiological factors Studies to identify such factors are underway. The few studies with children with BPD suggest a dysfunction in neural circuitry in the amygdala, striatal, thalamic, and prefrontal structures of the brain (1). Neuropsychological factors A curious study has shown that children and adolescents with BPD may make more mistakes in facial emotion recognition compared with controls. For example, when shown adult faces, children with BPD report the faces as angry (1). These mistakes did not occur when shown children s faces. Adults with BPD make similar interpretations. Diagnosis and Clinical Features Diagnosis in children is not easy due to the difficulty in ascertaining the facts when taking the history and due to differences in interpretation of symptoms. Most children are not aware of the details about their symptoms and it is difficult for them to identify the time of onset and duration of symptoms. This makes taking the history of present illness difficult, although parents help a lot in this aspect. Another conflict is one of interpretation. Who decides what actions are developmentally appropriate versus those that are pathologic? For example, if a 4-year-old says that she is superwoman, is this just her imagination or she displaying grandiosity? Also, since the DSM-IV-TR criteria for diagnosing children with BPD is the same as that for adults, three schools of thought have arisen to solve this problem. Some say that the definition of BPD in children should be expanded; others claim that the definition should be tightened; and others have come up with a new diagnosis called Severe Mood Dysregulation (SMD). Expanding the definition Geller et al. describes what manic episodes with elevated mood look like in children. Other than presenting with irritability, to be diagnosed with BPD the children had to exhibit elevated or expansive mood or be grandiose. He proposed that manic looked different in children and adults, and the DSM criteria should be modified to allow mania diagnosis in a child who is a rapid cycler (2). Woziak et al. and Biederman et al. described what irritability looks like in children. Children meet the criteria for BPD if they presented with chronic irritability (2). There are many critics of these two views stating that many children exhibit labile mood and irritability as normal childhood behavior, and that

these symptoms should appear in clear and distinct episodes in order to be diagnosed as mania. Tightening the definition Some researchers have come up with two categories of BPD in children: narrow phenotype BPD and broad phenotype BPD. Narrow phenotype BPD is essentially the same as Bipolar I disorder. Broad phenotype BPD has been given to children without the episodes that distinguish bipolar I disorder. These children may eventually develop Bipolar II disorder, dysthymia, major depression disorder (MDD), or another disruptive behavior disorder. Severe Mood Dysregulation These debates led Leibenluft et al. to propose that some children may be better off with a different diagnosis called Severe Mood Dysregulation (SMD) (3). The diagnosis of SMD replaces broad phenotype BPD. Brotman et. al. described children who have severe irritability and hyperarousal symptoms but demonstrate chronic irritability and do not have the elevated mood or grandiosity. Children show reactivity to negative emotional stimuli, such as outbursts characterized by screaming or violent acts, occurring more than three times per week and is inappropriate for age. Symptoms must cause impairment in at least two settings (home, school, peers), and must exhibit symptoms for one year with no more than two symptom-free months, and with onset before 12 years of age (2). Rich et. al. found that when playing frustrating games, the brains of children with SMD and BPD respond differently as measured by EEG (2). Critics of the new SMD diagnosis says that the diagnosis of attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) already encompass these children. Regardless, authors of DSM-V are considering adding a new diagnostic category based on SMD and will possibly be called Temper Dysregulation Disorder with Dysphoria (TDD) (2). Comorbid conditions The high degree of psychiatric comorbidity in BPD in children makes this diagnosis even more difficult. Comorbidity with ADHD is present in 60%-90% of children, and has many diagnosis criteria in common (distractibility, hyperactivity, and talkativeness). However, even when the overlapping symptoms are removed from the diagnostic count, 89% of children with bipolar disorder continue to meet the full criteria of ADHD, demonstrating that both conditions are present (1). Comorbidity with Conduct Disorder (CD) is seen in 48%-69% of children (1). According to Biederman, physical restlessness and poor judgment are most common in comorbid CD. Comorbid anxiety disorders, especially panic disorder, is common. There is an estimated 21% lifetime prevalence of panic disorder with bipolar disorder versus 0.8% lifetime prevalence in those without mood disorder (1). These patients are also more likely to abuse alcohol and commit suicidal acts (1).

Pathology and Laboratory Examinations No specific laboratory findings are currently useful in the diagnosis of earlyonset BPD. Differential Diagnosis When deciding on a diagnosis of BPD in children and adolescents, other causes of symptoms must be ruled out. A full work-up should be undertaken to rule out a general medical conditions such as temporal lobe epilepsy, cerebral trauma, cerebral neoplasm, encephalitis, and vitamin deficiency, among others. If substance abuse is suspected, urine toxicology may be considered. Medications, such as steroids, causing manic symptoms should also be ruled out. Other conditions that should be considered are ADHD, ODD, obsessive-compulsive disorder (OCD), CD, MDD, adjustment disorder, learning disorder, pervasive developmental disorder (PDD), post-traumatic stress disorder (PTSD), and mental retardation. Some researchers claim that children are now receiving the diagnosis of BPD when in the past they would have received one of these differential diagnoses. Course and Prognosis Whether the natural history of early-onset BPD is the same as adult-onset is under investigation. A recent longitudinal study of 263 children with BPD followed for about two years found that about 70% recovered from their index episode within those two years (1). About 50% had at least one recurrence of a mood disorder during this time (usually a depressive episode). Approximately 58% changed polarity more than ten times per year and 30% changed polarity 20 times per year (1). The predictors of rapid cycling are: lower socioeconomic status (SES), presence of lifetime psychosis, and a previous diagnosis of BPD not otherwise specified (NOS). Research conducted by Birmhamer suggests that low SES is predictive of worse long-term bipolar outcome (2). Furthermore, longitudinal studies have demonstrated that when BPD is found in young children, recovery rates are lower (2). Treatment Only very few randomized, placebo controlled treatment trials have been conducted with children and youth. Treatment of children with BPD has been poorly successful thus far. Pharmacotherapy is the first-line of treatment, with psychosocial treatment being used as a compliment. In children, controlled trials have provided evidence suggesting that lithium is effective in the management of aggression behavior disorders. Open trials and retrospective chart reviews of children with BPD suggests that valproate (Depacon) is effective in the treatment of mania in children. A recent randomized clinical trial comparing divalproex (Depakote) and quetiapine (Seroquel) in the treatment of 50 adolescent patients with mania suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms and quetiapine may work quicker (1). More investigation is needed to confirm whether it can be used as monotherapy. An open trial of another atypical antipsychotic, risperidone (Risperal) has been shown to be effective in treating

mania in children. Other trials using risperidone and lithium/valproate suggest this combination to be effective in treating mania. An open trial of olanzapine used for eight weeks in treating childhood BPD found improvement in mania and depression at doses 2.5mg-20mg per day (1). An open-label trial of lamotrigine (Lamictal) in the treatment of BPD depression among adolescents provides preliminary support for its use in children and adolescents. Critics of using these pharmacological interventions mention the safety risks of these medications, for example, the risk a child developing juvenile diabetes as a result of taking an atypical antipsychotic. Since much investigation is still underway, the effectiveness of these treatments are also an issue of controversy. The research of Miklowitz with children and adolescents has demonstrated that one or more of the following psychosocial therapies should accompany pharmacotherapy for early-onset BPD: 1) family focused psychoeducational treatment (FFT), 2) Interpersonal and social rhythm therapy (IPSRT), 3) Cognitivebehavioral therapy (CBT), 4) Psychoeducation. He states that the goals of each treatment individually are not always clear, but the targets of there therapies are: stress and trauma management, modifying treatment adherence (compliance), improving family and peer relationships, improving ability to recognize and act on prodromal symptoms, teaching children problem-solving skills, teaching parents to reward positive child behavior. Miklowitz also recommends 12 or more sessions of psychosocial therapy (2). The issues with such therapies are the high cost and the commitment that is required of the child, family, and therapist. Lastly, it is important to treat comorbid psychiatric conditions, such as ADHD. Ethics Psychiatrist should be open about the shortcoming of the diagnosis and treatment of BPD in children. Parents should be told that the diagnostic criteria in children is not well established and that the medications used for treatment are not well tested in children for efficacy and safety. Another ethical concern for psychiatrist is whether they should diagnose a child with BPD with the purpose of insurance companies covering the cost of office visits and medication. Lastly, the diagnosis of BPD carries a stigma in the minds of the patient, their family members, and in the society. The label of BPD should be applied sparingly, keeping in mind the repercussions it may have on the child, family, and others. Conclusion The diagnosis of Bipolar Disorder in children is difficult because it remains poorly defined. The DSM-IV-TR has not helped to solve the problem, since it does not have individual diagnostic criteria for diagnosing children. Further complicating the problem, mania does not usually present as distinct episodes in children. Instead they may present as chronically irritable or as rapid cyclers. In adolescents there may even be psychotic symptoms. When a diagnosis is not clear, treatment may be compromised. Therefore, we have children that are symptomatic, while clinicians do not have clear guidelines on how to best treat them. To alleviate these problems a

new diagnosis, called severe mood dysregulation, has been proposed, and is thankfully being considered by the authors of the DSM-V. This will hopefully alleviate the problem and encourage more research on how to better treat these children and adolescents.

References 1. Sadock, Benjamin J., and Virginia A. Sadock. Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/clinical Psychiatry. Philadelphia: Wolter Kluwer/Lippincott Williams & Wilkins, 2007. 2. Parens, Erik, and Josephine Johnston. "CAPMH | Full Text | Controversies concerning the Diagnosis and Treatment of Bipolar Disorder in Children." Child and Adolescent Psychiatry and Mental Health. The Hastings Center, 10 Mar. 2010. Web. 17 Jan. 2012. <http://www.capmh.com/content/4/1/9>. 3. Brotman, Melissa A., Layla Kassem, Michelle M. Reising, Amanda E. Guyer, Daniel P. Dickstein, Brendan A. Rich, Kenneth E. Towbin, Daniel S. Pine, Francis J. McMahon, and Ellen Leibenluft. "PsychiatryOnline | American Journal of Psychiatry | Parental Diagnoses in Youth With Narrow Phenotype Bipolar Disorder or Severe Mood Dysregulation." PsychiatryOnline | The American Journal of Psychiatry | Home. 1 Aug. 2007. Web. 17 Jan. 2012. <http://ajp.psychiatryonline.org/article.aspx?articleID=98799>.