Children of Parents With Bipolar Disorder at High Risk for Earlier Onset, More Comorbidity

Deborah Brauser

November 11, 2009

November 11, 2009 (Honolulu, Hawaii) — Genetic and neurobiological mechanisms, including the serotonin transporter (SERT) gene, may increase the risk of development and progression of bipolar disorder (BD) in children born to parents with BD, new research suggests.

Presented here at the American Academy of Child & Adolescent Psychiatry 56th Annual Meeting, the study also showed that more than 33% of these high-risk children who had attention-deficit/hyperactivity disorder (ADHD) and/or other mood symptoms at baseline developed BD within 3 to 5 years. In addition, the age at onset for those with BD was an average of 6 years earlier than for their parents.

"It appears these families displayed genetic anticipation, which is the idea that each successive generation will have a disorder earlier and more severely," study investigator Meghan Howe, LCSW, MSW, told conference delegates. Ms. Howe is manager of the Pediatric Bipolar Disorder Program at Stanford University School of Medicine in California, under the direction of Kiki Chang, MD.

Controversial Territory

"We really do believe that anticipation is happening, although this is controversial territory, with some people not believing in it," Ms. Howe told Medscape Psychiatry after the session. "But when I look at the data and you listen to the kids that are suffering at a much earlier age, we can't just blame the environment and the toxins for everything. There's something genetic going on here."

Past studies have shown up to 50% of the offspring of parents with BD have a psychiatric disorder, with BD, ADHD, and major depressive disorder (MDD) being the most common diagnoses.

At Stanford, Dr. Chang oversees a large, ongoing study of BD offspring, with a particular focus on treatment effects, as well as neuroimaging. So far, 213 families with at least 1 biological parent with BD and 419 offspring between the ages of 6 and 17 years have been enrolled in the study.

In addition to genetic testing for SERT, study participants are interviewed to assess family and medication history and age at onset, which is defined as the time to the nearest month of the first hypomanic or manic episode.

For this study, investigators conducted follow-up interviews with 95 children (mean age, 11 years) 3 to 5 years after baseline assessment to evaluate variables that might influence the age at onset and increase the risk of progression.

Baseline and Follow-up Diagnoses in BD Offspring

Diagnosis Number at Baseline Number at Follow-up
Children with BD    
BD I 23 34
BD II 4 4
Total 27 38
Children at risk for BD    
High functioning 15 9
Other or mild impairment 8 3
ADHD or ADHD and mood 12 13
MDD 9 15
MDD and ADHD 19 3
BD NOS 5 14
Total 68 57
ADHD = attention-deficit/hyperactivity disorder; BD = bipolar disorder; MDD = major depressive disorder; NOS = not otherwise specified

"When analyzing the longitudinal data on the at-risk children, we found 54% had switched to more severe diagnostic categories at follow-up, and 30% of those switched to [BD] 1 or 2," said Ms Howe.

A greater proportion of the patients who converted had an S allele of SERT at 76% vs 35% of those who did not convert (> .001).

The mean ± SD number of reported stressful life events for all the children was 3.02 ± 1.5 and did not differ between those who converted to a more severe diagnosis and those who did not. The top 4 stressors were a parent's psychiatric hospitalization, academic problems, being bullied, and suicidal thoughts. The number of suicidal thoughts increased in all groups except for the high-functioning and mild impairment groups.

Although there were only 7 psychiatric hospitalizations experienced by the children with BD at baseline, that number increased to more than 20 within 5 years.

ADHD, Depression Precursors to Bipolar Disorder?

Children whose parents had both BD and ADHD had an earlier age at onset than children whose parents did not have comorbid ADHD (= .01).

In addition, children with BD had a significantly earlier age at onset at a mean ± SD of 11.1 ± 3.5 years vs 17.5 ± 7.4 years for their parents.

Furthermore, children experienced more instances of psychosis or psychiatric episodes at 33% vs 26% for their parents. Compared with their parents, they also had higher rates of ADHD (84% vs 52%) and BD 1 (79% vs 53%).

"Our results show BD is a highly heritable disorder and that ADHD and depression are common precursors to it," said Ms. Howe.

"These kids are getting worse and our research shows this. Why? Looking at the etiology of bipolar, I believe that genetics plays a big role and may be a big risk for these children. Obviously, something's going on.

"We need to look much further at this, but genetic and neurobiological markers may eventually help us to determine the risk for familial bipolar and to come up with preventative interventions that may be neuroprotective."

Ms. Howe said that the idea of screening or treating patients before they show symptoms has been considered controversial, and obtaining funding for that focus can be difficult.

Valuable Insights

Asked by Medscape Psychiatry to comment on the study findings, Russell E. Scheffer, MD, professor and chair, Department of Psychiatry and Behavioral Sciences at the University of Kansas School of Medicine in Wichita, said that the study should offer valuable information about BD and may eventually provide insight into the value of preclinical treatment. Dr. Scheffer was not involved in the research.

"The data [from the main study] with 400 children is amazing. And there are millions of things [the researchers] could do with it. I think that the combination of genetics and neuroimaging that could potentially predict progression or treatment outcomes could be incredible," he said.

"They now know that the ADHD/major depression group had a lot of the swings to bipolar disorder. So further looking at that group and seeing if there were any predictive indicators of who's going to switch and when would provide information as to the key time to intervene," he said.

The study was supported by the National Institute of Mental Health and the Heinz C. Prechter Fund. Ms. Howe and Dr. Scheffer have disclosed no relevant financial relationships.

American Academy of Child & Adolescent Psychiatry 56th Annual Meeting: Abstracts 18.2 and 18.1. Presented October 31, 2009.

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