Researchers are looking for better ways of predicting whether children at risk for bipolar disorder will go on to develop the illness. A 2015 study by David Axelson and colleagues in the American Journal of Psychiatry reported that in the offspring of parents with bipolar disorder, diagnoses of sub-threshold mania, depression, and disruptive behavior disorders were associated with subsequent diagnosis of full-blown Bipolar I or Bipolar II disorders six to seven years later.
More recently, in an article by Danella M. Hafeman and colleagues in the American Journal of Psychiatry, the same group of investigators has examined how symptoms (rather than categorical diagnoses, as in the earlier study) predict the development of bipolar disorder. In children and adolescents at high risk for bipolar disorder (because they have a parent with the disorder) three types of symptoms were the best predictors of later bipolar disorder: anxiety/depression at the time participants entered the study, unstable mood or irritability both when entering the study and shortly before a bipolar diagnosis, and low-level manic symptoms observed shortly before diagnosis.
The earlier the age at which a parent was diagnosed with a mood disorder, the greater the risk that the offspring would also be diagnosed with bipolar disorder. Youth with all four risk factors (anxiety or depression, mood changes, low-level mania, and a parent who was diagnosed with a mood disorder at an early age) had a 49 percent chance of developing bipolar disorder, compared to a 2 percent chance among those without those risk factors.
Childhood onset of bipolar disorder and long delays until first treatment for depression or mania are both significant predictors of a poor outcome in adulthood compared to adult onsets and shorter delays to treatment. Read more
The Course and Outcome of Bipolar Youth study, or COBY, has been collecting information on young people with bipolar disorder and tracking their symptoms into adulthood since 2000. A 2015 study by Benjamin I. Golstein in the Journal of Clinical Psychiatry analyzed COBY data, identifying links between higher than average levels of inflammatory markers measured in the blood and participants’ histories of illness and familial risk factors.
High levels of the inflammatory marker hsCRP were associated with longer duration of illness, substance use disorder, and family history of suicide attempts or completed suicides. High levels of TNF-alpha were linked to suicide attempts, self-injury behaviors, and family history of substance use disorders. IL-6 was also linked to family history of substance use disorders.
There were also links between inflammatory markers and participants’ symptoms over the 6 months leading up to the blood tests. Levels of the inflammatory marker TNF-alpha were linked to the percentage of weeks patients had psychotic symptoms. Levels of IL-6 were associated with percentage of weeks with subthreshold mood symptoms and also with any suicide attempt. Levels of HsCRP were linked to maximum severity of depressive symptoms.
It is possible that targeting the elevated levels of inflammatory markers with anti-inflammatory treatments could improve patients’ response to treatments, but this topic requires further study.
Vitamin D3 tends to be low in children and adolescents with mania, but supplements may help. In a small open study published in the Journal of Child and Adolescent Psychopharmacology in 2015, Elif M. Sikoglu and colleagues administered 2000 IU of vitamin D3 per day to youth aged 6–17 for eight weeks. Sixteen of the participants had bipolar spectrum disorders (including subthreshold symptoms) and were exhibiting symptoms of mania. Nineteen participants were typically developing youth.
At the beginning of the study, the youth with bipolar spectrum disorders had lower levels of the neurotransmitter GABA in the anterior cingulate cortex than did the typically developing youth. Following the eight weeks of vitamin D3 supplementation, mania and depression symptoms both decreased in the youth with bipolar spectrum disorders, and GABA in the anterior cingulate cortex increased in these participants.
Editor’s Note: GABA dysfunction has been implicated in the manic phase of bipolar disorder. While larger controlled studies of vitamin D supplementation are needed, given the high incidence of vitamin D deficiency in youth in the US, testing and treating these deficiencies is important, especially among kids with symptoms of bipolar illness.
Lithium is the treatment of choice for adults with bipolar disorder, but has rarely been studied in children or adolescents. One of the first double-blind placebo-controlled trials of lithium for the treatment of mania in children and teens aged 7–17 showed that the drug produced greater improvement in mania than did placebo. Side effects included blurred vision, abdominal pain, diarrhea, nausea, vomiting, fatigue, thirst, increased thyroid-stimulating hormone, decreased appetite, dizziness, sedation, tremor, increased urination, and rash.
In the study by researcher Adelaide S. Robb and colleagues, which was presented at the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, doses began at 300mg twice a day, were based on each child’s weight, and were slowly increased.
At the same meeting, researcher Russell Scheffer presented data on 41 children who continued lithium treatment for 16 weeks with good results. The mean dose was 27.8 +/- 6.7 mg/kg per day.
At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Melissa P. DelBello reported that compared to placebo, the anticonvulsant topiramate reduced marijuana craving in young people aged 12–21 who were already taking the antipsychotic quetiapine. Functional magnetic resonance imaging (fMRI) revealed that topiramate altered the activation of brain regions common to both drug craving and mood dysregulation. Topiramate could be a good treatment to reduce marijuana abuse. The antioxidant n-acetylcysteine (NAC) is another option.
Researcher Juan David Palacio reported at the 2015 meeting of the American Academy of Child and Adolescent Psychiatry that compared to offspring of non-ill parents, children of parents with bipolar I disorder are at high risk for psychiatric disorders, particularly bipolar spectrum disorders and substance use disorders. They were also at risk for symptoms of anxiety disorders and conduct disorder. Palacio’s findings from Colombia mirror those from other studies of familial risk and suggest the importance of vigilance to detect these disorders early and provide appropriate treatment. Our Child Network may help.
Bipolar disorder in childhood or adolescence can destroy academic, family, and peer relationships and increase vulnerability to drug use, unsafe sexual encounters, disability, and suicide. Treatment is critical to avoid cognitive decline. Given the potential tragic outcomes of undertreating bipolar illness, it is concerning that 40–60% of children and adolescents with bipolar disorder are not in treatment.
In a talk at the 2015 meeting of the International Society for Bipolar Disorder, researcher Cristian Zeni reviewed the existing research on the treatment of bipolar disorder in children and adolescents. A 2012 study by Geller reported response rates of 68% for the atypical antipsychotic risperidone, 35% for lithium and 24% for valproate. Risperidone was linked to weight gain and increases in prolactin, a protein secreted by the pituitary gland, while lithium was linked to more discontinuations and valproate to sedation.
For children or adolescents with aggression, researcher Robert Kowatch recommends quetiapine, aripiprazole, and risperidone. For those with a family history of bipolar disorder, he recommends lithium or alternatively, valproate plus an atypical antipsychotic.
Reseacher Robert Findling has found that lamotrigine has positive effects in childhood mania, and Duffy et al. found in a study of 21 children with mania that 13 remained stable on monotherapy with quetiapine for 40 weeks without relapse, while 5 others required combination treatment with more than one drug. In studies by Karen Wagner, oxcarbazepine was significantly better than placebo at reducing mania in younger children (ages 7–12), but not older children (13–18).
Studies by Duffy and colleagues in 2007 and 2009 recommend lithium for those with a family history of bipolar disorder, atypical antipsychotics for children with no family history of bipolar disorder, and lamotrigine for those with a family history of anxiety disorders.
In children with bipolar disorder and comorbid attention deficit hyperactivity disorder, there is universal agreement that mood should be stabilized first, and then small amounts of stimulants may be added for residual ADHD symptoms. Too often, the opposite occurs, with stimulants given prior to mood stabilization with lithium, anticonvulsants (valproate, lamotrigine, carbamazepine/oxcarbazepine) and/or an atypical antipsychotic. Read more
Adolescents whose parents have a history of depression are at greater risk for depression themselves. A new study suggests that a cognitive-behavioral prevention program aimed at these teens can reduce depression rates compared to the usual care.
The study, by David A. Brent and colleagues in the journal JAMA Psychiatry, included 316 participants aged 13–17, each of whom had a parent with a current or prior depression. Half of the participants participated in the cognitive-behavioral prevention program in addition to usual care initiated by their families. The program consisted of 8 weeks of 90-minute group sessions focused on developing positive thinking habits and improving problem solving, followed by six monthly sessions. The training was based on the Adolescents Coping with Depression program described in a June 2009 JAMA article by Garber et al.
The group who participated in the prevention program had a lower incidence of depression than the group who received only the usual care, and this difference persisted over six years of followup. Most of this effect was due to a reduced incidence of depression in the first nine months following the intervention. (Depression was roughly equal among the two groups at two later followups.)
Importantly, the benefit of the prevention program was only seen among adolescents whose parents were not depressed at the time of enrollment in the study, underscoring the importance of treating parents in order to keep the whole family healthy.
Benefits of the prevention program included reductions in onset of depression and days depressed, and improvement in interpersonal and academic competence.
Brent and colleagues say that the study shows that it is possible to prevent depression, and this can have long-term developmental consequences. They encourage focusing on the entire family’s mental health treatment.
While the main benefits came early, Brent suggests that booster sessions for teens who begin to show symptoms of depression might refresh the benefits of the prevention program at a later time.
Editor’s Note: This study has enormous health implications as depression in adolescents tends to recur and is associated with a more difficult course than depression beginning in adulthood. Preventing depressions would theoretically have positive consequences for both psychiatric and physical health, as depression is associated with increased risk of suicide and decreased longevity from increases in cardiovascular disease. Researcher Joan Luby recently reported that children with prepubescent onset of depression have decreased hippocampal volume in adolescence, so it is possible that preventing depression may have positive implications for brain volume and function.
Childhood onset bipolar disorder can be highly impairing. Treatment usually includes medication, but several types of psychotherapy have also been found to be superior to treatment as usual. These include family focused therapy, dialectical behavior therapy and multifamily psychoeducation groups, including Rainbow therapy.
Family focused therapy, developed by David Miklowitz, consists of psychoeducation about bipolar disorder and the importance of maintaining a stable medication routine. Families are taught to recognize early symptoms of manic and depressive episodes, and how to cope with them. Families also learn communication and problem solving skills that can prevent stressful interactions.
Dialectical behavior therapy was developed by Marsha Linehan, initially for the treatment of borderline personality disorder. It can be useful in bipolar disorder because participants learn how to manage stressors that might otherwise trigger depression or mania. DBT teaches five skills: mindfulness, distress tolerance, emotion regulation, interpersonal effectiveness, and self management.
Multifamily psychoeducation was developed by Mary Fristad. In groups, children and parents learn about mood disorders, including how to manage symptoms, and also work on communication, problem solving, emotion regulation, and decreasing family tension.
Rainbow therapy is a type of multifamily approach also known as child and family-focused cognitive-behavioral therapy (CFF CBT). It integrates individual cognitive-behavioral therapy with family psychoeducation and mindfulness skills training. In a recent article in the journal Evidence Based Mental Health, Miklowitz reviewed the current research on Rainbow therapy. While the research to date has many limitations, he highlighted some benefits of Rainbow therapy: its flexibility, and its focus on treating parents’ symptoms along with children’s illness.
The atypical antipsychotic asenapine has been reformulated for bipolar I disorder in children aged 10–17. The drug (trade name Saphris) was approved by the Food and Drug Administration (FDA) in 2009 for adults with schizophrenia and bipolar disorder. It is sometimes used as a treatment for mixed episodes (depression with some symptoms of mania).
The new formulation consists of 2.5mg tablets that are taken sublingually (under the tongue), and are available in a black cherry flavor. These can be prescribed as monotherapy for the acute treatment of manic or mixed episodes in children and teens.