VIENNA — Individuals born to younger or older parents are at increased risk of developing bipolar disorder, new research suggests.
Results from a meta-analysis of more than 210,000 patients with bipolar disorder and over 13 million healthy individuals showed that children of mothers younger than 20 years had a 23% increased risk for bipolar disorder vs those whose parents were aged 25-29 years. For participants whose mothers were aged 35-39 years, there was a 10% increased risk for bipolar disorder, which rose to 20% if the mother was age 40 or older.
Having a father younger than 20 years conferred a 29% increased risk for bipolar disorder, which was the same increase in risk found in individuals whose fathers were aged 45 years or older.
These findings, which are an update of data published earlier this year in the journal European Pharmacology, were presented here at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
14 Studies Included
Previous studies have suggested that parental age at birth is a risk factor for several psychiatric disorders in offspring, including bipolar disorder, and that advanced parental age, specifically, is associated with earlier onset schizophrenia.
To investigate further, the current researchers conducted a systematic review and meta-analysis, searching the PubMed/MEDLINE, EMBASE, Scopus, and PsychINFO databases for relevant studies published to December 1, 2021.
From 712 studies initially identified, 16 met all the inclusion criteria and 14 were included in the quantitative analysis.
Five studies reported only paternal age and risk for bipolar disorder in their offspring, one included just maternal age, and eight reported both maternal and paternal age in relation to the risk for offspring bipolar disorder.
Individuals with a history of any psychiatric disorders were excluded, leaving a total of 13.4 million individuals without bipolar disorder and 217,089 who had received a diagnosis for the disorder.
The investigators also corrected for both socioeconomic status and, when assessing the impact of maternal or paternal age at birth, corrected for the age of the other parent. However, they were unable to correct for the number of children in a family.
Results after stratifying maternal and paternal age showed that, compared with those born to parents aged 25-29 years, there was an increased risk for bipolar disorder in the offspring of both fathers and mothers younger than 20 years of age, with adjusted odds ratios (ORs) of 1.29 (95% CI, 1.13 - 1.48) and 1.23 (95% CI, 1.14 - 1.33), respectively.
Compared with those aged 25-29 years, there was also an increased risk for bipolar disorder in children born to mothers aged 35-39 years (adjusted OR, 1.1; 95% CI, 1.01 - 1.19) and aged 40 or older (OR, 1.2; 95% CI 1.02 - 1.40).
Among fathers, there was increased risk for offspring bipolar disorder in those aged 45 or older vs those aged 25-29 years (adjusted OR, 1.29; 95% CI, 1.15 - 1.46).
There are several hypotheses that could explain the results, lead study author Giovanna Fico, MD, Bipolar and Depressive Disorders Unit, Hospital Clínic Barcelona, Spain, told Medscape Medical News.
In older age, it may be "more related to genetic or epigenetic modification, especially in fathers," Fico said. "Some studies have shown that there are de novo mutations in the germ lines, which increase the risk of several diseases, including schizophrenia."
In younger individuals, there could be a "mixed effect between sociocultural factors, such as use of substance abuse, low educational status," and other issues, Fico noted.
Moreover, as bipolar disorder onset can be as late as 30 years of age, the younger group could include "undiagnosed patients with bipolar disorder, which would increase the risk" of the disease in their offspring, she added.
Fico noted the investigators are now planning on studying the impact of environmental factors such as pollution, climate change, and urbanization on risk for bipolar disorder, with the aim of being better able to inform parents or to develop prevention strategies.
Psychoeducation is "very common for infertility, birth defects, and Down syndrome, but it's not so common for psychiatric disorders because we need more data. But I think it's important that parents know they have an increased risk," she said.
Nevertheless, "We must stress that this risk is moderate, and it must be kept in perspective," Fico said in a news release.
"Exciting" Questions Raised
The study "raises several exciting research questions, including the possibility of early prevention and intervention," Maj Vinberg, MD, PhD, clinical professor, Department of Clinical Medicine, University of Copenhagen, Denmark, said in the release.
Commenting to Medscape Medical News, she said she agrees there are likely to be different factors at play at different ages, with the risk for bipolar disorder associated with younger age parenthood more likely to be related to socioeconomic status.
For older parents, "there has been a lot of speculation around the father's age especially, which everybody thought didn't matter," said Vinberg, who was not involved with the research.
"But you might have some epigenetic changes as you grow older that might transfer into the next generation," given that there is 20 years of additional exposure to potential epigenetic changes between a man aged 25 years and one aged 45 years, she noted.
Vinberg also highlighted that there could be cases of undiagnosed bipolar disorder among the younger parents, and she noted that "men with bipolar disorder tend to have more children," particularly during manic phases.
She explained that if someone were to get divorced at 35 years of age, then have a new manic episode at 45 "and have a new wife and children, I don't know whether it's possible to correct for that."
The research is supported by a fellowship from "La Caixa" Foundation. The investigators have reported no relevant financial relationships. Vinberg reported having relationships with Lundbeck and Janssen.
35th European College of Neuropsychopharmacology (ECNP) Congress: Abstract P.0468. Presented October 17, 2022.
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Cite this: 'U-Shaped' Relationship Between Bipolar Risk and Parental Age - Medscape - Oct 17, 2022.