Relatively little attention has been paid to the children of a parent with bipolar disorder, who are at risk not only for the onset of bipolar disorder, but also anxiety, depression, and multiple other disorders. These children deserve a special focus, as on average 74.2% will receive a major (Axis 1) psychiatric diagnosis within seven years.
New research published by David Axelson and colleagues in the American Journal of Psychiatry describes a longitudinal study comparing children who have a parent with bipolar disorder to demographically matched children in the general public. Offspring at high risk for bipolar disorder because they have a parent with the disorder had significantly higher rates of subthreshold mania or hypomania (13.3% versus 1.2%) or what is known as bipolar disorder not otherwise specified (BP-NOS); manic, mixed, or hypomanic episodes (9.2% versus 0.8%); major depressive episodes (32.0% versus 14.9%); and anxiety disorders (39.9% versus 21.8%) than offspring of parents without bipolar disorder. Subthreshold episodes of mania or hypomania (those that resemble but do not meet the full requirements for bipolar disorder in terms of duration) were the best predictor of later manic episodes. This finding was observed prospectively, meaning that patients who were diagnosed with manic episodes during a follow-up assessment were likely to have been diagnosed with a subthreshold manic or hypomanic episode during a previous assessment.
The study included 391 children (aged 6–18) of at least one bipolar parent, and compared these to 248 children of parents without bipolar disorder in the community. The participants took part in follow-up assessments every 2.5 years on average, for a total of about 6.8 years. Each follow-up assessment included retrospective analysis of symptoms that had occurred since the previous assessment.
In addition to having more subthreshold manic or hypomanic episodes; manic, mixed, or hypomanic episodes; and major depressive episodes, the high-risk children also showed more non-mood-related axis 1 disorders, including attention deficit hyperactivity disorder (ADHD), disruptive behavior disorders, and anxiety disorders than the children of parents without bipolar disorder. Axelson suggested that monitoring for these symptoms may help with early identification and treatment.
Children with a bipolar parent were diagnosed with bipolar spectrum disorders at rates of 23% compared to 3.2% in the comparison offspring. Mean age of onset of mania or hypomania in the high-risk offspring was 13.4 years. Of those offspring who had a manic episode, more than half had the episode before age 12, with the earliest occurring at age 8.1.
Compared to previous studies of children of parents with bipolar disorder, this study found that the mean age of onset of manic or hypomanic episodes was younger, possibly because other studies did not include young children. Another new finding was that major depressive episodes were risk factors for mania and hypomania but did not always precede the onset of mania or hypomania in the high-risk offspring.
Parents of children who are at high risk for developing bipolar spectrum disorders should be aware of the common precursors to mania—subthreshold manic or hypomanic symptoms and non-mood disorders—and make sure that clinicians assess for these symptoms and differentiate them from the symptoms of depression or other disorders.
Editor’s Note: In Axelson’s study, 74.2% of the offspring of a bipolar parent suffered a major (Axis I) psychiatric disorder. However, 48.4% of the offspring from the comparison group of community controls also had an Axis 1 psychiatric disorder. These high rates of illness and dysfunction indicate the importance of monitoring a variety of symptom areas and getting appropriate evaluation and treatment in the face of symptoms that are associated with impairment in both high risk children and in the general population.
One way of doing this is for parents to join our new Child Network, a study collecting information about how children at risk for bipolar disorder or with symptoms of bipolar disorder are being treated in the community and how well they are doing. Parents rate their children on a weekly basis for depression, anxiety, ADHD, oppositionality, and mania-like symptoms. Parents will be able to produce a longitudinal chart of their children’s symptoms and response to treatment, which may assist their child’s physician with early detection of illness and with treatment. See here for more information and to access informed consent documents.
A new study finds that omega-3 fatty acid supplementation improves attention in boys both with and without attention deficit hyperactivity disorder (ADHD). The study by Dienke J. Bos and colleagues in the journal Neuropsychopharmacology included 40 boys (aged 8–14) with ADHD and 39 demographically matched controls. Participants were given 10 g per day of margarine supplemented with either omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) or placebo.
The children who received EPA/DHA supplementation showed improvements in attention (as rated by parents) compared to those who received placebo. Improvement was greater in the children with ADHD. Supplementation did not affect cognitive control or brain activity on functional magnetic resonance imaging (fMRI). Those boys who received omega-3s showed higher DHA levels on followup.
Studies have found that when a depressed mother’s symptoms remit, her children are less likely to show psychiatric symptoms. A new study by Myrna M. Weissman and colleagues in the American Journal of Psychiatry randomized 76 mothers to treatment with escitalopram, bupropion, or a combination of the two, and assessed the impact of the mothers’ treatment on their 135 children (aged 7–17).
There were no significant differences in the mothers’ symptoms or remission, but children’s depressive symptoms and functioning improved more if their mothers received (only) escitalopram. Only in that group was a mother’s improvement associated with her children’s improvement.
Mothers in the escitalopram group reported greater improvement in their ability to listen and talk to their children compared to the mothers in other groups, and the children of the mothers in the escitalopram group reported that their mothers were more caring.
Children of mothers with low negative affect improved significantly, while children of mothers with high negative affect only improved if their mothers were in the escitalopram group.
The authors suggest that for a mother’s improvement to help her children’s symptoms, her anxious distress and irritability must be reduced, and these may be better targeted with escitalopram than bupropion.
Children who have a parent with bipolar disorder are at risk for bipolar illness, but it may first present as depression. Treating these children with antidepressants has the risk of bringing on manic episodes. Researchers are looking for treatment options for youth at risk for bipolar disorder.
Robert McNamara and colleagues found that 12 weeks of omega-3 fatty acids (2,100 mg/day) significantly improved response rates in medication-free youth ages 9–20 years compared to placebo (64% versus 36%). Omega-3 fatty acids but not placebo also reduced the activation of limbic structures in the brain (the left parahippocampal gyrus) in response to emotional stimuli.
Editor’s Note: These data add to the literature on the positive effects of 1–2 grams of omega-3 fatty acids in depression. Given the safety of omega-3 fatty acids and the ambiguous effects of antidepressants in bipolar depression, omega-3 fatty acids would appear to a good alternative, especially since the FDA-approved atypical antipsychotics (quetiapine and lurasidone) are not approved for bipolar depression in people under age 18.
Rodents that are subjected to social defeat (being overpowered by a bigger, more aggressive animal) develop a syndrome that resembles human depression—they avoid social interaction, lose interest in sucrose, and do less exploring of new places or other animals. A recent finding showed that even witnessing the social defeat of a peer was enough to bring about the depressive behaviors. The same researchers, led by Samina Salim, recently found that young rats (aged 21–27 days) that witnessed their mother go through the trauma of social defeat showed depression-like behavior themselves as adults (at age 60 days).
The rats saw their mothers defeated by the larger rat every day for seven days. As adults, those who witnessed this abuse exhibited depression-like behavior compared to rats of the same age and gender that had not witnessed abuse. The depressive rats gave up more quickly on a test of forced swimming. Male rats showed great depression-like behavior than female rats.
It has been estimated by the American Psychological Association that 15.5 million children in the US witness physical or emotional abuse of a parent (usually their mother). Children who witness domestic violence often show symptoms of post-traumatic stress disorder (PTSD). This rodent research may lead to a better understanding of the consequences of witnessing trauma in childhood, and potential treatments that could help.
Editor’s Note: These data show that rats have something like empathy, and that the psychological aspects of stress (including verbal abuse in humans and witnessing another’s abuse in rodents) may have profound and lasting consequences on behavior.
In a poster at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Larissa Portnoff reported that NF-kB, a marker of inflammation that can be measured in two types of white blood cells (lymphocytes and monocytes), was significantly elevated in adolescents who had bipolar disorder compared to healthy control participants.
Several other inflammatory markers have been linked to bipolar disorder, including c-reactive protein (CRP) and TNF alpha. The new data about NF-kB suggests that another inflammatory pathway is overactive in the disorder. NF-kB levels did not correlate with the severity of manic or depressive symptoms, as do levels of some other inflammatory markers.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Robert Findling reported on a double blind, placebo controlled 36-week study of lamotrigine for children and adolescents with bipolar I disorder. The doses designed for maintenance treatment averaged about 225 mg/day, achieved by very slow increases over time in order to reduce the risk of a serious rash.
Findling found that lamotrigine was more effective than placebo in extending the time until a patient required an intervention for a new mood episode among the older children in the study (aged 13 to 17). Among the younger children in the study (aged 10 to 12), lamotrigine’s effects were not statistically significant compared to placebo. Findling and colleagues concluded that lamotrigine appeared effective in delaying time to onset of a new episode in adolescents with bipolar I disorder.
Lamotrigine is approved by the Federal Drug Administration (FDA) for bipolar disorder in adults only.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Adelaine Robb reported that in 81 children with mania (aged 7-17), lithium was superior to placebo in reducing the severity of mania measured on the Young Mania Rating Scale. There had been some debate about the efficacy of lithium in young children with mania, but this study clearly indicates lithium’s effectiveness. The drug is approved by the Federal Drug Administration (FDA) for use in patients with bipolar disorder aged 12 and up.
Another researcher, Vivian Kafrantaris, found that in children who averaged 14.5 years of age, lithium increased the volume of the corpus callosum, a bundle of neural fibers that connects the brain’s right and left hemispheres. Lithium also normalized white matter integrity in other neural fiber tracts—the cingulum bundle and the superior longitudinal fasciculus. The authors concluded that lithium may “facilitate microstructural remodeling of white matter tracts involved in emotional regulation.”
Editor’s Note: There is much research showing that in adults, lithium has positive effects on the brain, including increases in hippocampal and cortical grey matter volume. Now it appears that lithium can improve white matter integrity in the developing brain as well.
Researcher Amanda Roten reported at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry that adolescents who stopped heavy marijuana use showed improvements in multiple areas of learning and memory. These data support previous findings that pot can cause impairments in cognitive functioning, but that abstaining from the drug can bring about improvement relative quickly.
These data contrast with some others. A 2009 study by J. Jacobus et al. in the journal Pharmacology Biochemistry and Behavior suggested that some changes in brain structure resulting from marijuana use, such as decreases in cortical volume, can persist for one to three months following abstinence.
Madeline Meier, another researcher at the meeting, reported that 1,037 participants who used marijuana persistently from about age 13 to age 38 lost an average of 8 IQ points. Controlling for years of education and other potential confounds such as alcohol and drug use did not affect these findings. Moreover, Meier found that “cessation of cannabis use did not fully restore IQ among adolescent-onset cannabis users.”
Editor’s Note: The popular view that marijuana is a benign substance overlooks some key facts. The main pharmacological effect of pot is an amotivational syndrome, causing apathy and lack of drive to participate in work, study, and other activities. Heavy use of pot doubles the risk of psychosis, and this risk is further increased if a user has a common genetic variation in the enzyme catechol-o-methlyl transferase (COMT), which metabolizes dopamine. The more efficient allele of COMT (known as val-56-val, identifying two valine amino acids) lowers frontal cortex dopamine more, and increases the risk of delusions and hallucinations. Marijuana alters brain structure and impairs memory. It may now be legal in some states, and while reducing penalties for smoking marijuana may be a good idea, this does not mean the drug is a harmless substance.
The moral of the story is that avoiding marijuana use in the first place, especially for people with bipolar disorder, should make it easier to get well and stay well. For current marijuana users, N-acetylcysteine (NAC, a nutritional supplement available without a prescription from health food stores) has been shown to help adolescents decrease marijuana use more than placebo.
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.