Both bipolar disorder and unipolar depression often begin in childhood or adolescence, but it can be difficult to distinguish the two using symptoms only. People with bipolar illness may go a decade without receiving a correct diagnosis. Researcher Jorge Almeida and colleagues recently performed a meta-analysis of previous studies to determine what neural activity is typical of children with bipolar disorder versus children with unipolar depression while processing images of facial emotion. They found that youth with bipolar disorder were more likely to show limbic hyperactivity and cortical hypoactivity during emotional face processing than youth with unipolar depression. Almeida and colleagues hope that this type of data may eventually be used to diagnose these disorders or to measure whether treatment has been successful.
Three articles in the September 2014 issue of the journal Psychiatric Annals (Volume 44 Issue 9) discussed differentiating pediatric bipolar disorder from attention deficit hyperactivity disorder (ADHD). The first article, by Regina Sala et al., said that reasons to suspect bipolar disorder in a child with ADHD include:
- The ADHD symptoms appear for the first time after age 12.
- The ADHD symptoms appear abruptly in an otherwise healthy child.
- The ADHD symptoms initially responded to stimulnts and then did not.
- The ADHD symptoms come and go and occur with mood changes.
- A child with ADHD begins to have periods of exaggerated elation, grandiosity, depression, decreased need for sleep, or inappropriate sexual behaviors.
- A child with ADHD has recurring severe mood swings, temper outbursts, or rages.
- A child with ADHD has hallucinations or delusions.
- A child with ADHD has a strong family history of bipolar disorder in his or her family, particularly if the child does not respond to appropriate ADHD treatments.
The second article, by this editor Robert Post, Robert Findling, and David Luckenbaugh, emphasized the greater severity and number of symptoms in childhood onset bipolar disorder versus ADHD. Children who would later develop bipolar disorder had brief and extended periods of mood elevation and decreased sleep in the early years of their lives. These, along with pressured speech, racing thoughts, bizarre behavior, and grandiose or delusional symptoms emerged differentially from age three onward. In contrast, the typical symptoms of ADHD such as hyperactivity, impulsivity, and decreased attention were equal in both diagnoses.
In the third article, Mai Uchida et al. emphasized the utility of a family history of bipolar disorder as a risk factor. Moreover, a child with depression plus ADHD is at increased risk for a switch into mania on antidepressants if there is a family history of mood disorders, emotional and behavioral dysregulation, subthreshold mania symptoms, or psychosis.
The differential diagnosis of ADHD versus bipolar disorder (with or without comorbid ADHD) is critical, as drug treatment of these disorders is completely different.
Bipolar disorder is treated with atypical antipyschotics; anticonvulsant mood stabilizers, such as valproate, carbamazepine, or lamotrigine; and lithium. Only once mood is stabilized should small doses of stimulants be added to treat residual ADHD symptoms.
ADHD, conversely, is treated with short- or long-acting stimulants such as amphetamine or methylphenidate from the onset, and these may be augmented by the noradrenergic alpha-2 agonists guanfacine or clonidine. The selective noradrenergic re-uptake inhibitor atomoxetine is also approved by the Federal Drug Administration (FDA) for the treatment of ADHD. The dopamine-active drug bupropion and the anti-narcolepsy drugs modafinil and armodafinil have mild anti-ADHD effects but have not been FDA-approved for that purpose.
At the 2014 meeting of the International Society for Bipolar Disorders, researcher B.N. Kim discussed symptoms that could distinguish between bipolar disorder and attention deficit hyperactivity disorder (ADHD) in childhood. Both disorders are characterized by decreased attention, concentration, and frustration tolerance, and increased activity, impulsiveness, and irritability.
Kim shared several differential symptoms that are more indicative of a bipolar diagnosis and that are inconsistent with a simple ADHD diagnosis (and this editor Robert Post has added several more). Signs and symptoms that suggest bipolar disorder and not ADHD include: decreased need for sleep, brief and extended periods of euphoria, hypersexuality, delusions, hallucinations, suicidal or homicidal impulses and/or actions, extreme aggression, and multiple areas of extreme behavioral dyscontrol. ADHD, on the other hand, is characterized by more difficulty focusing attention, and by less extreme symptoms in general.
An article published by N. Drancourt et al. in the journal Acta Psychiatra Scandinavica this year examined the duration of the period between a first mood episode and treatment with a mood stabilizer among 501 patients with bipolar disorder. The time between a first episode of depression, mania, or hypomania and first treatment averaged 9.7 years. The authors conclude that more screening, better recognition of the early stages of the illness, and greater awareness are needed to decrease this long delay.
Editor’s Note: The article by Dancourt et al. replicates earlier findings of an average treatment delay of 10 years among bipolar patients from the treatment network in which this editor (Robert Post) is an investigator (formerly the Stanley Foundation Bipolar Network, now called the Bipolar Collaborative Network). The duration of the untreated interval (DUP) for patients with bipolar disorder is unacceptably long and carries a heavy price.
Those with the earliest age of onset experience the longest delay to first treatment. Early onset is associated with poor outcome compared to adult onset bipolar disorder, and the duration of time untreated adds a separate, independent risk of a worse outcome in adulthood, especially more frequent and severe depression, more episodes, and less time well.
What patients and doctors can do to shorten this interval to first treatment: Know the risk factors for early onset bipolar disorder so you can seek evaluation and advise treatment as appropriate. Read more
It is hoped that measuring biochemical substances in blood will help in the diagnosis of mood disorders and help direct patients to the most effective therapeutic regimens. J.L. Billbielo reported at the 51st Annual Meeting of the National Institute of Mental Health’s New Clinical Drug Evaluation Unit (NCDEU) in 2011 that investigators from Ridge Diagnostics in North Carolina were using this type of biomarker panel in an attempt to provide a predictive algorithm for a diagnosis of major depressive disorder. The panel of 10 assays was derived from a larger screening set and included: alpha 1 antitrypsin (Alpha 1AT), brain-derived neurotrophic factor (BDNF), cortisol, epidermal growth factor (EGF), resistin, and soluble tumor necrosis factor receptor II (sTNFR2). The research group found that this optimized algorithm distinguished depressed subjects from normal controls with a sensitivity of approximately 90% and a sensitivity of 84%.
Editor’s note: This assay is available commercially and appears to represent an interesting panel of potential neurobiological markers of depression, including neurotrophic factors, endocrine stress hormones, and inflammatory markers. While its diagnostic utility is somewhat doubtful and must be further demonstrated, this editor hopes that similar panels could ultimately predict individual clinical response to a given treatment. For example, patients with high levels of inflammatory markers might respond better to treatments aimed at suppressing inflammation. Read more
Kathleen Merikangas of the National Institute of Mental Health (NIMH) gave a plenary presentation on developmental manifestations of the bipolar spectrum at the 2011 Pediatric Bipolar Disorder Conference in Cambridge, Massachusetts this past March, which was sponsored by Massachusetts General Hospital and the Ryan Licht Sang Foundation. There were several striking take-away messages from her epidemiological research. She found that:
- Rates of bipolar disorder in childhood were relatively similar to rates among adults
- Only 22% of youth with bipolar spectrum diagnoses actually obtained mental health treatment for their conditions
- There was no evidence that these children were being over-medicated, as some non-epidemiological reports had suggested
She also reported that those with subthreshold bipolar spectrum disorders, i.e. those not meeting strict criteria for BP-I (including full-blown mania) or BP-II (including hypomania for four or more days) still were very ill and had considerable disability and dysfunction.
Merikangas reported on interviews of 10,123 youth aging from 13 to 18 found in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), and found rates of illness among the youth similar to those seen in adults. However, these children with bipolar spectrum disorders were more than ten times more likely to be on antidepressants than mood stabilizers, and more than four times more likely to be on antidepressants than atypical antipsychotics, again suggesting these children were not receiving the treatments recommended by consensus guidelines.
David Axelson from Western Psychiatric Institute and Clinic gave a plenary talk on temper dysregulation disorder (TDD) with dysphoria at the 2011 Pediatric Bipolar Disorder Conference, held in Cambridge, Massachusetts in March. Researchers in the field have been discussing whether a diagnosis of TDD or severe mood dysregulation (SMD), a name Ellen Liebenluft of the National Institute of Mental Health has used to describe a similar behavior pattern, is necessary and should be included in the upcoming fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
The rationale for including a TDD or SMD diagnosis was the upsurge in the diagnosis of bipolar disorder among children. Researchers like Liebenluft believed that bipolar disorder was being over-diagnosed in children, and that some children could instead be classified as having a disorder that was limited to chronic irritability. Temper dysregulation disorder is what researchers eventually settled on. Post-hoc analysis of longitudinal epidemiological studies suggested that some chronic irritability experienced by children and adolescents developed into depressive and anxiety disorders rather than bipolar disorder.
However, as described in the epidemiological data of Merikangas et al. (which we will post later this week) and others, the frequency of youth diagnoses of bipolar disorder are not out of proportion with the number of diagnoses in adults. Now that it does not seem likely that bipolar disorder is being over-diagnosed among children, there is less rationale for the new diagnosis categories. In addition, it seems that TDD may not even capture a specific set of behaviors or symptoms. Read more
An article by Geller et al. in Bipolar Disorders last year illustrates the crisis in the treatment of childhood-onset bipolar illness in the US. The article indicates that almost 40% of the children with a credible diagnosis of bipolar disorder in this study never received anything near the appropriate treatment for their illness.
It is unfortunate when children fail to receive appropriate treatment because of ambiguity about a diagnosis, but it is even more frustrating when one of the world’s experts makes a diagnosis, and a child still fails to receive treatment based on consensus guidelines.
Over 8 years of follow-up treatment in their communities, these very ill children not only did not receive helpful drugs such as atypical antipsychotics or mood stabilizers, but they often received treatments that can be counterproductive, such as antidepressants or psychomotor stimulants. Those children who did receive appropriate treatment with lithium fared better and recovered significantly earlier than the others. Read more
Consistent Deficits In Facial Emotion Recognition Found in Non-Ill Children of Parents with Bipolar Disorder
Children with bipolar parents may have difficulty identifying the emotions they see on another person’s face. Aditya Sharma of Newcastle University presented a poster at the Pediatric Bipolar Conference in Cambridge, Massachusetts in March, which indicated that children without bipolar disorder but at risk because a parent has the illness showed deficits in facial emotion recognition. Similar results were reported by Brotman et al. in the American Journal of Psychiatry in 2008. Since children of bipolar parents are at increased risk of developing the disease, this deficit in labeling facial emotion may be a marker of early bipolar disorder or a risk factor for its onset.
Editor’s Note: These types of deficits in facial emotion recognition have been consistently observed in adults and children diagnosed with bipolar disorder, so assessing whether children can successfully identify others’ facial emotions could become part of the assessment of risk for bipolar disorder. This deficit could also be targeted for psychosocial intervention and rehabilitative training to enhance emotion recognition skills. Such an approach could improve interpersonal communication and lessen hypersensitive responses to perceived emotional threats and negative emotional experiences.