Thursday, November 15, 2012

Study : Fecundity of People With Mental Disorders

According to a recent study, people who have schizophrenia, autism, and anorexia nervosa have fewer children than the general population.  This isn't a particularly happy topic or one that I enjoy dwelling on, but it is a rather important topic to think about when trying to understand whether autism is becoming more common.

One the one hand you have the idea that autism is strongly genetic and runs in families but on the other you have the inconvenient fact that having autism greatly reduces your chances of having children.  You would think that those ideas aren't compatible, that the families who have a higher than normal number of members with autism would not keep going generation after generation as they would be "strongly selected against".

Of course the issue isn't really that simple as that.  There are many other factors involved that might be contributing to these families staying around such as extremely mild symptoms of autism, recessive traits, the relative rarity of autism, and the like that could explain both facts.

But still, even if both ideas are true and autism is strongly genetic and "strongly selected against", you would, at best, expect it to stay about the same prevalence.  It would look more like schizophrenia which is "genetic" (and environmental), runs in families, and is "strongly selected against" and still manages to stay at a relatively constant 1% of the population.

Yet with autism we have three ideas that really can't go together - that autism is strongly genetic, that autism makes you a lot less likely to have children, and that the number of cases of autism is growing fairly rapidly.  Although to be fair, all three of these statements are gross oversimplifications of the complex realities of autism.

Just food for thought.  The abstract of the study is below.

Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings

Context  It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants.

Objectives  To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants.

Design  We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population.

Setting  Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register.

Participants  In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden.

Main Outcome Measures  Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status.

Results  Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals.

Conclusions  Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.

Power RA, Kyaga S, Uher R, Maccabe JH, Långström N, Landen M, McGuffin P, Lewis CM, Lichtenstein P, Svensson AC. Fecundity of Patients With Schizophrenia,  Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings. Arch Gen Psychiatry. 2012 Nov 12:1-8. doi: 10.1001/jamapsychiatry.2013.268. [Epub ahead of print] PubMed PMID: 23147713


  1. One issue you've neglected to discuss as well as probably the authors of the article on "fecundity" as to why autism stays in the population though they have limited children is de novo or new mutations. Sometimes genes spontaneously mutate and aren't inherited or they spontaneously mutate in the parents without autism and they pass it in to their progeny. Also, some forms of autism with known etiology such as tuberous sclerosis are transmitted by autosomal dominance so there is a 50% chance of carrier having it.

    Also, some disabilities such as shadow forms of ADHD and depression could be genetically related to autism, such as my grandmother who comitted suicide a few years before I was born due to severe depression and who now has 16 descendants including me. I suspect her genes were partially to blame for my autism and I have some cousins who are also her grandchildren with shadow forms of ADHD one who has two children (the other has been married but never had kids). Though I'm not an expert on genetics, I suspect that and other things provide an explanation for the fecundity stuff and that article does not really prove anything.

    I suspect part of the reason autism is increasing is that parents are more commonly having children at advanced ages and that has something to do with it, so that the DNA in a 40+ male's sperm is more likely to be defective and he is more likely to have an autistic offspring than someone younger.

    Also I suspect many more people are being diagnosed for commercial reasons among ABA specialists and special educators and the criteria for diagnosis has become looser and more arbitrary.

    1. Hi Jonathan,

      You raise some good points but I am not sure I agree with you.

      The genetic methods of autism transmission, even if they are rare mutations that only show up once and a while, should not lead to a higher number of cases of autism unless the mutations are becoming more common. And, even if they mutations were becoming more common, the number of cases should not be expanding so quickly. It would take multiple generations for the numbers to increase so much.

      The same thing applies for de novo mutations. Either the number of mutations per unit of the population is staying relatively constant - as would be expected for a stable "random" process - or that number is increasing. If the number is somewhat stable then these mutations can't account for the increase in the number of cases of autism. If the numbers of mutations per unit of population are increasing then we aren't dealing with a "random" process (a process isn't random if it shows a clear trend) and we should be trying to figure out why.

      The only way I can see the genetic line of thinking agreeing with the number of cases increasing so quickly is if the problematic genetics are becoming much more common very quickly and, in the absence of some external factor, that should not happen.

      Yes, some of the increase is bound to be due to social factors but even the most pie in the sky estimates can only account for roughly half of the growth over the past twenty years and yet the number of people with autism is still growing rapidly every year.

      So I think my point is this. Even the basic facts that autism is strongly genetic and is increasing at a pretty good clip are hard to reconcile. When you add in the fact that the families that appear to have the strongest genetic link to autism are also the ones that are going to disappear most quickly, I think the argument falls apart.

      Think of it this way, the more likely you are to have autism via some form of genetic inheritance, the less likely you are to pass on your genetics to another generation. The only way mutations like this can survive in the face of being "strongly selected against" is if it the harmful effects are relatively rare. But we are seeing the exact opposite trend in autism.

  2. Increased age would be the male counterpart to Trisomy 21, which goes from something like one in 2000 to one in 300 with increased maternal age.

    Also I suspect many more people are being diagnosed for commercial reasons among ABA specialists and special educators and the criteria for diagnosis has become looser and more arbitrary.

    Hear, hear! It may not be "intentional", but it is the way of the world.