Recent research shows that children born to fathers under the age of 20, or those born to mothers over the age of 35 and fathers over the age of 45, are at higher risk of being diagnosed with bipolar disorder later in life. Older men, researchers report, are at higher risk of having a child with bipolar disorder.
Bipolar disorder, in which sufferers can swing between euphoric and extremely depressed states, is one of the most common serious mental illnesses, affecting about 2 percent of people and carrying a high risk of suicide and premature death. It is known to be highly heritable; if a parent has bipolar disorder, there is a 15 percent to 30 percent chance that it will be passed on to their children.
A basic tenet of psychiatry is that the phenotype of the illness results from a combination of genetic and environmental effects. However, genetics only explains part of the etiology of BD, so a growing body of evidence has linked several environmental elements that may influence BD risk.
The wide range of environmental risk factors varies according to the timing of exposure and can include pre- or perinatal factors, adverse childhood experiences, infections, as well as urbanization, migration, major stressful life events, and drug or alcohol misuse.
Globally, environmental factors contribute up to 32% of TB risk, proving to be attractive, potentially modifiable targets for preventive strategies. Parental age is a well-known factor involving both environmental and genetic contributions that impact the risk of several disorders in offspring.
Both extremes of reproductive age have been associated with worse outcomes, whether relative to maternal age, paternal age, or both. A notable example is the higher risk of Down syndrome in older mothers, while a younger childbearing age is associated with lower educational attainment, juvenile crime, substance abuse, and mental health problems.
Advanced paternal age at birth has been associated with a higher incidence of several neurodevelopmental and psychiatric disorders, including schizophrenia and autism spectrum disorders.
The mechanisms underlying these relationships are not fully understood, with findings suggesting a role for de novo mutations in the male germline or even an increased likelihood of pregnancy complications, which are more common with later fatherhood.
In addition, advanced paternal age appears to increase the risk of early-onset psychosis due to the possible role of age-related DNA mutation accumulation. However, there is still conflicting evidence on the association between advanced parental age and risk of BD in offspring, with some large studies proving a positive association between advanced paternal age and risk of BD, while others have shown no significant association.
Given the increasing trend in average paternal age, elucidating such an association may have social and public health implications. Furthermore, evidence of the effects of parental age on BD risk may provide insights into the etiology of this complex and multifactorial disorder.
Therefore, the first objective of this systematic review and meta-analysis, published in European Neuropsychopharmacology, is to determine whether parental age is associated with an increased risk of BD in offspring.
In addition, considering that early-onset bipolar disorder presents homogeneous features and that specific risk factors may operate in this subgroup, a secondary objective is to assess whether advanced parental age is associated with an earlier onset of bipolar disorder.
The researchers, from Spain, Italy, Australia, and the Netherlands, conducted a systematic review of studies from several countries that relate bipolar disorder to age. In total, the studies included 13,424,760 participants, of whom 217,089 had bipolar disorder.
The results showed that children of younger or older parents have a higher risk of bipolar disorder. This risk is higher if you were born to a mother or father under 20 if your mother was over 35 or your father was over 45. This trend gives a ‘U-shaped curve’, showing higher risks for younger and older fathers.
They found that older men were more likely than other groups to have a child with bipolar disorder. These men were 29% more likely to have a baby with bipolar disorder than fathers aged 25 to 29, while older women were 20% more likely than mothers aged 25 to 29.
In fathers under 20, the increased odds were 23% (for mothers) to 29% (for fathers). All analyses were corrected for biases such as the family history of bipolar disorder and the age of the other parent.
The U-shaped relationship between parental age and the risk of bipolar disorder in offspring. In pink, maternal age, and green, paternal age. Data presented at the European College of Neuropsychopharmacology Conference. P.0468 and published in doi: 10.1016/j.euroneuro.2022.05.004
Study leader Dr Giovanna Fico, from the University of Barcelona, said: “Parental age is a factor that affects many conditions, such as fertility and some neuropsychiatric disorders. What we found is a bit unusual because both younger and older fathers have a higher risk of having a child with bipolar disorder. The higher risk is moderate, but real.
We can speculate that younger fathers may be affected by environmental factors, such as socioeconomic problems, and lack of support, but also stress or immunological factors, and that older fathers may have genetic factors coming into play, but the truth is that we don’t know.”
The study raises several interesting research questions, including the possibility of early prevention and intervention. For example, in everyday clinical settings, it is crucial to be aware that young individuals with BD in their manic phases have more risky sexual behavior, which may be associated with an increased risk of pregnancy.
Again, it should be emphasized that this risk is moderate and should be kept in perspective. However, for those already at risk, age is another factor that should be taken into account, and therefore clinicians may need to counsel younger and older couples if they are at risk of bipolar disorder. We also see this U-shaped curve in some other conditions, such as autism and some cardiovascular diseases.
There is a need to inform individuals about the risk of early or late reproductive age and implement interventions to reduce psychosocial stressors in adolescent parents, as well as programs to follow up on offspring at risk of developing BD.
Further studies are needed to elucidate the cause-and-effect relationship and the mechanism between parental age and increased risk of BD in offspring.
READ MORE:
The U-shaped relationship between parental age and the risk of bipolar disorder in the offspring: A systematic review and meta-analysis
G. Fico, V. Oliva , M. De Prisco, A. Gimenez, M. Sagué-Vilavella, S. Gomes Da-Costa, M. Garriga, E. Solé , G. Fanelli, A. Serretti , M. Fornaro, A. Murru1, and E. Vieta.
Eur Neuropsychopharmacol. 2022 Jul:60:55-75. doi: 10.1016/j.euroneuro.2022.05.004.
Abstract:
Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We searched the MEDLINE, Scopus, Embase, PsycINFO online databases for original studies from inception, up to December 2021. Random-effects meta-analyses were conducted. Sixteen studies participated in the qualitative synthesis, of which k = 14 fetched quantitative data encompassing a total of 13,424,760 participants and 217,089 individuals with BD. Both fathers [adjusted for the age of other parent and socioeconomic status odd ratio - OR = 1.29(95%C.I. = 1.13-1.48)] and mothers aged ≤ 20 years [(OR = 1.23(95%C.I. = 1.14-1.33)] had consistently increased odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Fathers aged ≥ 45 years [adjusted OR = 1.29 (95%C.I. = 1.15-1.46)] and mothers aged 35-39 years [OR = 1.10(95%C.I. = 1.01-1.19)] and 40 years or older [OR = 1.2(95% C.I. = 1.02-1.40)] likewise had inflated odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Early and delayed parenthood are associated with an increased risk of BD in the offspring. Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial, genetic, and biological factors, and with different impacts according to sex and age range. Evidence on the association between parental age and illness onset is still tentative but it points towards a possible specific effect of advanced paternal age on early BD-onset.
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