Referenced Article: “Bipolar Spectrum Disorders in Children and Adolescents ” The Carlat Child Psychiatry Report, Oct/Nov/Dec 2022
Dr. Feder: Bipolar disorder is challenging to diagnose in children and adolescents, yet timely and accurate diagnosis is crucial. Delayed diagnosis can result in ineffective treatment and substantial morbidity, while a misdiagnosis can risk unnecessarily exposing patients to medication side effects and inaccurate expectations of chronic illness. Despite ongoing controversies about BD in prepubertal children, there is a body of research specific to children and adolescents. In this episode, we will help unpack BD and offer recommendations for assessment.
Welcome to The Carlat Psychiatry Podcast.
This is another episode from the child psychiatry team.
I’m Dr. Josh Feder, The Editor-in-Chief of The Carlat Child Psychiatry Report and co-author of the new second edition of the The Child Medication Fact Book for Psychiatric Practice as well as the other co-authored Prescribing Psychotropics, also from Carlat Publishing.
Mara: And I’m Mara Goverman, a Licensed Clinical Social Worker in Southern California with a private practice.
Dr. Feder: We have some exciting news for you! You can now receive CME credit for listening to this episode and all new episodes going forward on this feed. Follow the Podcast CME Subscription link in the show notes to get access to the CME post-test for this episode and future episodes.
Mara: Let's begin by discussing what exactly the bipolar spectrum is. Many researchers use the term “bipolar spectrum disorder” or BPSD to include cases of bipolar I (BP I), bipolar II (BP II), cyclothymia, and what DSM-IV called “bipolar not otherwise specified” or BP-NOS. Childhood BP-NOS became operationalized by researchers to include cases where the manic episode had one fewer symptom than required for a “classic” manic episode, or the mood episode lasted at least four hours on a minimum of four separate days, compared to “classic” episodes that require symptoms to occur on consecutive days.
Dr. Feder, can you talk about any relevant studies discussing the diagnostic progression of youth with bipolar not otherwise specified disorder (BP-NOS)?
Dr. Feder: Yes, definitely. Over 15 years ago the multicenter Course and Outcome of Bipolar Youth aka COBY study recruited pediatric patients with an average age of 12 years with “subsyndromal” bipolar symptoms and followed them for several years. Within five years, about 45% went on to meet full criteria for bipolar I or bipolar II, while 41% continued to meet the “bipolar not otherwise specified” criteria. Only 14% of kids with bipolar not otherwise specified showed partial or full remission within five years. So think about that. Most of the kids continued to have significant difficulties. This broader definition of BD can capture many young people on their way to developing bipolar I or bipolar II; however, it is still up for debate whether this broader definition includes youth who are moody for other reasons. Well defined or not, bipolar not otherwise specified in youth requires intervention because these children have problematic symptoms and impairment similar to youth with BP I or BP II, including suicide attempts.
Mara: What are some of the strongest risk factors of the development of BD?
Dr. Feder: Family history of BD is among the strongest risk factors for its development. In children with a bipolar parent, also known as high-risk children, bipolar spectrum disorder emerges over years, usually by the mid-20s. The other thing to really watch for is that there can be developmental progression of symptoms in some kids. So it kind of starts with sleep and anxiety symptoms at younger ages from about 4 to 10 years old, and then stress sensitivity or minor depressive disorders in early adolescence ages from about 10 to 13 years old, major depression, psychosis, or nonresponse to SSRI in mid to late adolescence, and then finally hypomanic or manic episodes in late adolescence and early adulthood.
Mara: What about irritability?
Dr. Feder: That's a really good question. Early researchers studying pediatric BD suggest that chronic, intense irritability was a form of BD in prepubertal children. However, 20 years of research have soundly demonstrated that chronic irritability is distinct from bipolar disorder, and so DSM uses disruptive mood dysregulation disorder (DMDD) for youth with chronic severe irritability. Irritability can certainly be a prominent symptom in bipolar spectrum disorder, but the irritability must be episodic and must be accompanied by other symptoms of mania or depression to be considered part of the bipolar spectrum. But the chronic irritability is more of DMDD.
Mara: Another thing we need to think about is how prevalence rates of bipolar spectrum disorder differ between adolescents and children.
Rates of the more broadly defined bipolar spectrum disorder are much higher than rates of narrowly defined BD in children and adolescents, and this more pure form of bipolar spectrum disorder is far more common in adolescents than in younger children. Let’s unpack this a bit. For bipolar spectrum disorder, a meta-analysis of 19 prevalence studies, representing 56,103 subjects from 10 countries, estimated the bipolar spectrum disorder rate among adolescents at a whopping 8.3%, while it was only 1.7% among children under 12. These prevalence rates were similar across countries. For classic bipolar I in children and adolescents, this meta-analysis had 14 studies reporting on rates of bipolar I. Four of these studies had zero cases and three found just one to two cases. This meta-analysis found that among all the 19 studies the estimated rate of bipolar I was only 0.6%.
Dr. Feder: The controversy around this topic persists, particularly regarding heterogeneity in the underlying epidemiological studies. For example, in the studies that found any bipolar spectrum disorder, the rates of adolescent bipolar spectrum disorder ranged from 1.2% to 14.3%. This debate goes beyond child psychiatry, as there is active discussion among adult bipolar researchers about whether current DSM definitions are too restrictive, resulting in underdiagnosis of adult BD. For more information on diagnosing bipolar disorder in adults, see The Carlat Psychiatry Report, Nov/Dec 2021.
Mara: What about bipolar spectrum disorder in prepubertal children?
Dr. Feder: People agree more about rates of bipolar spectrum disorder in adolescence but there’s a lot of debate about bipolar spectrum disorder in prepubertal children. Five studies of genetically high-risk prepubertal children with one parent with bipolar disorder found no evidence of bipolar spectrum disorder. None. Zero. In contrast, US-based researchers consistently describe bipolar spectrum disorder in prepubertal children. Compared to other cohorts, US kids also have higher rates of comorbid attention deficit hyperactivity disorder (ADHD) and other disruptive behavior disorders, as well as higher rates of social adversity. These research differences are reflected in dramatic differences in inpatient discharge diagnosis. The US rates of discharge diagnosis of BD for 5- to 9-year-olds are hundreds of times higher than in several other countries.
Mara: Social inequity and trauma can also impact the diagnosis and treatment of BD.
In the US, Black adults and adolescents with BD tend to be misdiagnosed with schizophrenia and on top of that they tend to be undertreated with medication. And the opposite happens too. Economic disadvantage often results in lack of access to specialty care in the US, and this is associated with overdiagnosis and overtreatment of BD. For example, in Kentucky, 2.4% of 6-year-olds are prescribed antipsychotics, often with a diagnosis of BD, but the diagnosis and prescriptions are usually not made by child psychiatrists.
Additionally, social disadvantage brings childhood adversity, trauma, and psychopathology. Aggressive children with histories of trauma and social disadvantage have disruptions in mood, thought, and behavior, which contribute to overdiagnosis of BD, including in prepubertal children. And to complicate matters even more, childhood abuse, neglect, exposure to parental psychiatric symptoms, and attachment difficulties may all increase the risk of early onset of bipolar spectrum disorder.
So given the complexities surrounding the definition of bipolar conditions, what tools or tips can help us sort out the diagnosis?
Dr. Feder: It is really complicated, and you’re right Mara, we need to have some reliable ways to sort it all out. First look at risk factors, especially family history. Children of parents with BD have an estimated eight- to 10-fold higher lifetime risk of developing BD than the general population. Also make sure to ask about family treatment as lithium response has a genetic component.
Also check for that developmental trajectory of symptoms which might show you an unfolding syndrome. It doesn't happen in every kid, it is maybe a percentage and not even a majority, but when it is there it is interesting and you will want to be the one to spot it. And also look for substance use, which is so common too especially when there is mood instability and people are self medicating, and kind of a chicken and egg problem, where some kids try to settle themselves down with substances, others may be triggering their mood instability especially with withdrawal such as mood withdrawal, and both of those problems may be happening simultaneously.
You also need to think about other conditions that might be causing the symptoms. Differentiating bipolar spectrum disorder from disruptive mood dysregulation disorder, ADHD, posttraumatic stress disorder, or oppositional-defiant disorder requires attention to whether symptoms occur episodically or chronically. Ask multiple informants about the time course of symptoms, onset and resolution of the symptoms. Mood rating scales or checklists can help you and your patients more consistently identify those symptoms, but also improve diagnostic decisions and track treatment. The Parent General Behavior Inventory or the Child Mania Rating Scale are great examples of scales you might use. A good social history can identify maltreatment, trauma, or extreme adversity contributing to mood dysregulation and inform your differential diagnosis as well.
US researchers have developed a risk calculator that uses clinical symptoms and family risk factors to estimate the probability that a patient will meet full criteria for BD within five years; you can also use it periodically to track care. This approach may motivate families to watch for symptoms and return for follow-up. The calculator is available for free at: www.cabsresearch.pitt.edu/bpriskcalculator/
Mara: Can you talk a bit more about the relationship between substance use disorders and bipolar spectrum disorder?
Dr. Feder: Yes. Substance use disorders or SUDs occur in up to 33% of adolescent patients with BD, including alcohol, marijuana, and tobacco. This combination is associated with earlier onset of BD, severe symptoms, rapid cycling, and suicidality. One quick way you can assess for substance use symptoms is with a checklist such as the CRAFFT. That stands for Car; Relax; Alone; Forget; Friends; and Trouble. If your patient has a co-occurring substance use disorder, you need to treat both conditions together. For patients without substance use problems, talk to them and their parents about prevention strategies to avoid drug and alcohol use. For more resources about CRAFFT, co-occurring SUD, and prevention strategies you can click the links on our website.
Mara: Patients often feel demoralized by the time they are in the office. Sometimes they’ve spent years trying to help their child with little or no luck and sometimes getting worse. How should providers discuss the developmental course of mood symptoms with parents?
Dr. Feder: Explain to parents that the shifting symptoms and they are not responding to treatment, it might be part of this complicated illness and that it can take a long time for the symptoms of BD to become clearly visible.
Mara: So there you have it. Bipolar spectrum disorder is rare in prepubertal children, and bipolar I is vanishingly rare. Family history and history of adversity are important as are clear symptoms of mania and depression. There is vigorous debate about narrow vs broad definitions of BD. With no age-based standards for “appropriate levels'' of grandiosity, elation, or irritability, your diagnosis of bipolar spectrum disorder depends upon methodical assessment of symptoms, time course, episodic patterns, and family history. Manic symptoms often emerge from a developmental trajectory of symptoms, so reassess bipolar symptoms as patients age and explain to patients and their families that this might happen.
Dr. Feder: The newsletter clinical update is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully, people will check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits.
Mara: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry.
Dr. Feder: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us to bring you unbiased information that you can trust.
Thanks for listening and have a great day!