Some psychiatric disorders hamper ability to get pregnant

Some psychiatric disorders appear to be associated with lower fecundity in both men and women, suggesting that natural selection attempts to discourage the perpetuation of genetic variants associated with them.

Instead, new mutations could be one reason that the disorders continue to exist, Robert A. Power and his colleagues wrote in the January issue of JAMA Psychiatry (formerly Archives of General Psychiatry).

The authors also found that psychiatric disorders affected men’s fecundity more than women’s. "This sex-specific effect suggests that psychiatric morbidity impairs interest or ability to find suitable mating partners or inhibits biological fertility to a greater extent in men," wrote Mr. Power of Kings College, London.

The study data were extracted from two of Sweden’s population registries – the Multi-Generation Register and the Swedish Hospital Discharge Register. More than 2.3 million people born from 1950-1970 were cross-linked by individual patient identification numbers, which allowed the researchers to trace not only patients but also their siblings. At the time of the analysis, no patient was younger than 40 years (JAMA Psychiatry 2013;70:22-30).

The authors tracked fecundity in about 177,000 patients who had schizophrenia, autism, bipolar disorder, anorexia nervosa, or substance abuse. Rates were compared with fecundity in 261,000 siblings. The researchers then compared these rates with those found in the general population.

About 19,000 patients had schizophrenia. They had significantly fewer children than the general population’s (fecundity rate [FR] 0.23 for men and 0.47 for women). In a univariate analysis, sisters of the patients had a significantly higher fecundity rate (FR, 1.02), but this difference disappeared once comorbidities were factored into the analysis. Brothers also had significantly decreased fecundity (FR, 0.97).

"Our results suggest a strong selection pressure to remove genetic variants associated with schizophrenia from the population," the authors said. "This is further evidence for the role of recent or de novo mutations in the genetic susceptibility to schizophrenia that has neither reached the frequency of nor existed long enough to be removed from the population."

Autism was present in 2,947 patients; these had 4,471 siblings. Fecundity was significantly lower in both men and women (FR, 0.25 and 0.48, respectively). Among the siblings, brothers also had fewer children (FR, 0.94). Among sisters, the rate was not significantly different than the general population.

"Individuals with autism showed the greatest reduction in fecundity among all examined disorders. This was not unexpected because previous investigations have shown that few individuals with autism ever married or had children.

"We propose that rare highly deleterious variants and sexually antagonistic polymorphisms may contribute to the genetic disposition to autism. The similarity to schizophrenia is notable because it has been proposed that the autistic and psychotic spectrums reflect two extremes of social cognition."

Bipolar disorder was present in 14,439 patients, among whom were 22,986 siblings. Fecundity was significantly lower than the general population in both men (FR, 0.75) and women (FR, 0.85). While brothers had similar rates to that of the general population, sisters had significantly more children (FR, 1.03). But incorporating comorbidities into the analysis changed the significance for both patients and sisters, with the patient rate increasing to just below that of the general population (FR, 0.94), and the sisters’ rate increased rate no longer being significant (FR, 0.95).

"It has been suggested that the introduction of lithium as a treatment for bipolar disorder has led to improved functioning and, as a result, greater fecundity in those populations where treatment is available."

There were 81,295 patients with depression, among who were 119,645 siblings. While men with depression had significantly lower rates (FR, 0.93), women with the disorder were not significantly different than the general population. Siblings had significantly more children than the general population (FR, brothers 1.01, sisters 1.04) – a difference that was unchanged by factoring in comorbidities. The addition of comorbidities to the analysis did not change the decreased fecundity rate for male patients, but actually increased the rate for female patients (FR, 1.03).

"Notably, depression was an exception to the five other studied disorders ... genes associated with depression seems to be maintained in the population by balancing selection because the cost to affected individuals is roughly equal to the benefit to their siblings. If this is the case, it would be the first strong evidence for balancing selection in a psychiatric disorder."

There were 3,275 patients with anorexia, who had a total of 5,172 siblings. Both men and women with the disorder had significantly reduced fecundity (0.54 and 0.58, respectively). In the sibling group, there were no significant differences for either brothers or sisters. None of the findings changed when comorbidities were factored in.

"Our calculations suggest that anorexia is under weaker negative selection relative to schizophrenia and autism," the authors said.

Substance abuse was present in 55,933 patients, who had a total of 81,592 siblings. The fecundity rate was significantly lower in both men and women (FR, 0.78 and 0.93, respectively). Siblings had significantly more children than the general population (FR, 1.03 for brothers and 1.05 for sisters).

"Our findings suggest that this increased fecundity in siblings almost entirely accounts for the cost to affected individuals, with only a slight decrease in the frequency of these individuals’ genes predicted each generation. Considering that most drugs are a new environmental exposure when seen from an evolutionary perspective, it is possible that there has been insufficient time for selection to act on risk alleles. ... It has also been suggested that substance abuse is associated with risk-taking behavior in both sexes, including sexual risk taking."

The study was funded by the Medical Research Council of the United Kingdom. One of the coauthors reported having received consulting fees and honoraria from GlaxoSmithKline and Lundbeck.

[email protected]

Some psychiatric disorders appear to be associated with lower fecundity in both men and women, suggesting that natural selection attempts to discourage the perpetuation of genetic variants associated with them.

Instead, new mutations could be one reason that the disorders continue to exist, Robert A. Power and his colleagues wrote in the January issue of JAMA Psychiatry (formerly Archives of General Psychiatry).

The authors also found that psychiatric disorders affected men’s fecundity more than women’s. "This sex-specific effect suggests that psychiatric morbidity impairs interest or ability to find suitable mating partners or inhibits biological fertility to a greater extent in men," wrote Mr. Power of Kings College, London.

The study data were extracted from two of Sweden’s population registries – the Multi-Generation Register and the Swedish Hospital Discharge Register. More than 2.3 million people born from 1950-1970 were cross-linked by individual patient identification numbers, which allowed the researchers to trace not only patients but also their siblings. At the time of the analysis, no patient was younger than 40 years (JAMA Psychiatry 2013;70:22-30).

The authors tracked fecundity in about 177,000 patients who had schizophrenia, autism, bipolar disorder, anorexia nervosa, or substance abuse. Rates were compared with fecundity in 261,000 siblings. The researchers then compared these rates with those found in the general population.

About 19,000 patients had schizophrenia. They had significantly fewer children than the general population’s (fecundity rate [FR] 0.23 for men and 0.47 for women). In a univariate analysis, sisters of the patients had a significantly higher fecundity rate (FR, 1.02), but this difference disappeared once comorbidities were factored into the analysis. Brothers also had significantly decreased fecundity (FR, 0.97).

"Our results suggest a strong selection pressure to remove genetic variants associated with schizophrenia from the population," the authors said. "This is further evidence for the role of recent or de novo mutations in the genetic susceptibility to schizophrenia that has neither reached the frequency of nor existed long enough to be removed from the population."

Autism was present in 2,947 patients; these had 4,471 siblings. Fecundity was significantly lower in both men and women (FR, 0.25 and 0.48, respectively). Among the siblings, brothers also had fewer children (FR, 0.94). Among sisters, the rate was not significantly different than the general population.

"Individuals with autism showed the greatest reduction in fecundity among all examined disorders. This was not unexpected because previous investigations have shown that few individuals with autism ever married or had children.

"We propose that rare highly deleterious variants and sexually antagonistic polymorphisms may contribute to the genetic disposition to autism. The similarity to schizophrenia is notable because it has been proposed that the autistic and psychotic spectrums reflect two extremes of social cognition."

Bipolar disorder was present in 14,439 patients, among whom were 22,986 siblings. Fecundity was significantly lower than the general population in both men (FR, 0.75) and women (FR, 0.85). While brothers had similar rates to that of the general population, sisters had significantly more children (FR, 1.03). But incorporating comorbidities into the analysis changed the significance for both patients and sisters, with the patient rate increasing to just below that of the general population (FR, 0.94), and the sisters’ rate increased rate no longer being significant (FR, 0.95).

"It has been suggested that the introduction of lithium as a treatment for bipolar disorder has led to improved functioning and, as a result, greater fecundity in those populations where treatment is available."

There were 81,295 patients with depression, among who were 119,645 siblings. While men with depression had significantly lower rates (FR, 0.93), women with the disorder were not significantly different than the general population. Siblings had significantly more children than the general population (FR, brothers 1.01, sisters 1.04) – a difference that was unchanged by factoring in comorbidities. The addition of comorbidities to the analysis did not change the decreased fecundity rate for male patients, but actually increased the rate for female patients (FR, 1.03).

"Notably, depression was an exception to the five other studied disorders ... genes associated with depression seems to be maintained in the population by balancing selection because the cost to affected individuals is roughly equal to the benefit to their siblings. If this is the case, it would be the first strong evidence for balancing selection in a psychiatric disorder."

There were 3,275 patients with anorexia, who had a total of 5,172 siblings. Both men and women with the disorder had significantly reduced fecundity (0.54 and 0.58, respectively). In the sibling group, there were no significant differences for either brothers or sisters. None of the findings changed when comorbidities were factored in.

"Our calculations suggest that anorexia is under weaker negative selection relative to schizophrenia and autism," the authors said.

Substance abuse was present in 55,933 patients, who had a total of 81,592 siblings. The fecundity rate was significantly lower in both men and women (FR, 0.78 and 0.93, respectively). Siblings had significantly more children than the general population (FR, 1.03 for brothers and 1.05 for sisters).

"Our findings suggest that this increased fecundity in siblings almost entirely accounts for the cost to affected individuals, with only a slight decrease in the frequency of these individuals’ genes predicted each generation. Considering that most drugs are a new environmental exposure when seen from an evolutionary perspective, it is possible that there has been insufficient time for selection to act on risk alleles. ... It has also been suggested that substance abuse is associated with risk-taking behavior in both sexes, including sexual risk taking."

The study was funded by the Medical Research Council of the United Kingdom. One of the coauthors reported having received consulting fees and honoraria from GlaxoSmithKline and Lundbeck.

[email protected]

Some psychiatric disorders appear to be associated with lower fecundity in both men and women, suggesting that natural selection attempts to discourage the perpetuation of genetic variants associated with them.

Instead, new mutations could be one reason that the disorders continue to exist, Robert A. Power and his colleagues wrote in the January issue of JAMA Psychiatry (formerly Archives of General Psychiatry).

The authors also found that psychiatric disorders affected men’s fecundity more than women’s. "This sex-specific effect suggests that psychiatric morbidity impairs interest or ability to find suitable mating partners or inhibits biological fertility to a greater extent in men," wrote Mr. Power of Kings College, London.

The study data were extracted from two of Sweden’s population registries – the Multi-Generation Register and the Swedish Hospital Discharge Register. More than 2.3 million people born from 1950-1970 were cross-linked by individual patient identification numbers, which allowed the researchers to trace not only patients but also their siblings. At the time of the analysis, no patient was younger than 40 years (JAMA Psychiatry 2013;70:22-30).

The authors tracked fecundity in about 177,000 patients who had schizophrenia, autism, bipolar disorder, anorexia nervosa, or substance abuse. Rates were compared with fecundity in 261,000 siblings. The researchers then compared these rates with those found in the general population.

About 19,000 patients had schizophrenia. They had significantly fewer children than the general population’s (fecundity rate [FR] 0.23 for men and 0.47 for women). In a univariate analysis, sisters of the patients had a significantly higher fecundity rate (FR, 1.02), but this difference disappeared once comorbidities were factored into the analysis. Brothers also had significantly decreased fecundity (FR, 0.97).

"Our results suggest a strong selection pressure to remove genetic variants associated with schizophrenia from the population," the authors said. "This is further evidence for the role of recent or de novo mutations in the genetic susceptibility to schizophrenia that has neither reached the frequency of nor existed long enough to be removed from the population."

Autism was present in 2,947 patients; these had 4,471 siblings. Fecundity was significantly lower in both men and women (FR, 0.25 and 0.48, respectively). Among the siblings, brothers also had fewer children (FR, 0.94). Among sisters, the rate was not significantly different than the general population.

"Individuals with autism showed the greatest reduction in fecundity among all examined disorders. This was not unexpected because previous investigations have shown that few individuals with autism ever married or had children.

"We propose that rare highly deleterious variants and sexually antagonistic polymorphisms may contribute to the genetic disposition to autism. The similarity to schizophrenia is notable because it has been proposed that the autistic and psychotic spectrums reflect two extremes of social cognition."

Bipolar disorder was present in 14,439 patients, among whom were 22,986 siblings. Fecundity was significantly lower than the general population in both men (FR, 0.75) and women (FR, 0.85). While brothers had similar rates to that of the general population, sisters had significantly more children (FR, 1.03). But incorporating comorbidities into the analysis changed the significance for both patients and sisters, with the patient rate increasing to just below that of the general population (FR, 0.94), and the sisters’ rate increased rate no longer being significant (FR, 0.95).

"It has been suggested that the introduction of lithium as a treatment for bipolar disorder has led to improved functioning and, as a result, greater fecundity in those populations where treatment is available."

There were 81,295 patients with depression, among who were 119,645 siblings. While men with depression had significantly lower rates (FR, 0.93), women with the disorder were not significantly different than the general population. Siblings had significantly more children than the general population (FR, brothers 1.01, sisters 1.04) – a difference that was unchanged by factoring in comorbidities. The addition of comorbidities to the analysis did not change the decreased fecundity rate for male patients, but actually increased the rate for female patients (FR, 1.03).

"Notably, depression was an exception to the five other studied disorders ... genes associated with depression seems to be maintained in the population by balancing selection because the cost to affected individuals is roughly equal to the benefit to their siblings. If this is the case, it would be the first strong evidence for balancing selection in a psychiatric disorder."

There were 3,275 patients with anorexia, who had a total of 5,172 siblings. Both men and women with the disorder had significantly reduced fecundity (0.54 and 0.58, respectively). In the sibling group, there were no significant differences for either brothers or sisters. None of the findings changed when comorbidities were factored in.

"Our calculations suggest that anorexia is under weaker negative selection relative to schizophrenia and autism," the authors said.

Substance abuse was present in 55,933 patients, who had a total of 81,592 siblings. The fecundity rate was significantly lower in both men and women (FR, 0.78 and 0.93, respectively). Siblings had significantly more children than the general population (FR, 1.03 for brothers and 1.05 for sisters).

"Our findings suggest that this increased fecundity in siblings almost entirely accounts for the cost to affected individuals, with only a slight decrease in the frequency of these individuals’ genes predicted each generation. Considering that most drugs are a new environmental exposure when seen from an evolutionary perspective, it is possible that there has been insufficient time for selection to act on risk alleles. ... It has also been suggested that substance abuse is associated with risk-taking behavior in both sexes, including sexual risk taking."

The study was funded by the Medical Research Council of the United Kingdom. One of the coauthors reported having received consulting fees and honoraria from GlaxoSmithKline and Lundbeck.

[email protected]