Schizophrenia, Genes and Environment

Schizophrenia is generally thought of as the "most genetic" of all psychiatric disorders and in the past 10 years there have been heroic efforts to find the genes responsible for it, with not much success so far.A new study reminds us that there's more to it than genes alone: Social Risk or Genetic Liability for Psychosis? The authors decided to look at adopted children, because this is one of the best ways of disentangling genes and environment.

If you find that the children of people with schizophrenia are at an increased risk of schizophrenia (they are), that doesn't tell you whether the risk is due to genetics, or environment, because we share both with our parents. Only in adoption is the link between genes and environment broken.

Wicks et al looked at all of the kids born in Sweden and then adopted by another Swedish family, over several decades (births 1955-1984). To make sure genes and environment were independent, they excluded those who were adopted by their own relatives (i.e. grandparents), and those lived with their biological parents between the ages of 1 and 15. This is the kind of study you can only do in Scandinavia, because only those countries have accessible national records of adoptions and mental illness...

What happened? Here's a little graph I whipped up:

Brighter colors are adoptees at "genetic risk", defined as those with at least one biological parent who was hospitalized for a psychotic illness (including schizophrenia but also bipolar disorder.) The outcome measure was being hospitalized for a non-affective psychosis, meaning schizophrenia or similar conditions but not bipolar.

As you can see, rates are much higher in those with a genetic risk, but were also higher in those adopted into a less favorable environment. Parental unemployment was worst, followed by single parenthood, which was also quite bad. Living in an apartment as opposed to a house, however, had only a tiny effect.

Genetic and environmental risk also interacted. If a biological parent was mentally ill and your adopted parents were unemployed, that was really bad news.

But hang on. Adoption studies have been criticized because children don't get adopted at random (there's a story behind every adoption, and it's rarely a happy one), and also adopting families are not picked at random - you're only allowed to adopt if you can convince the authorities that you're going to be good parents.

So they also looked at the non-adopted population, i.e. everyone else in Sweden, over the same time period. The results were surprisingly similar. The hazard ratio (increased risk) in those with parental mental illness, but no adverse circumstances, was 4.5, the same as in the adoption study, 4.7.

For environment, the ratio was 1.5 for unemployment, and slightly lower for the other two. This is a bit less than in the adoption study (2.0 for unemployment). And the two risks interacted, but much less than they did in the adoption sample.

However, one big difference was that the total lifetime rate of illness was 1.8% in the adoptees and just 0.8% in the nonadoptees, despite much higher rates of unemployment etc. in the latter. Unfortunately, the authors don't discuss this odd result. It could be that adopted children have a higher risk of psychosis for whatever reason. But it could also be an artefact: rates of adoption massively declined between 1955 and 1984, so most of the adoptees were born earlier, i.e. they're older on average. That gives them more time in which to become ill.

A few more random thoughts:

• This was Sweden. Sweden is very rich and compared to most other rich countries also very egalitarian with extremely high taxes and welfare spending. In other words, no-one in Sweden is really poor. So the effects of environment might be bigger in other countries.
  
• On the other hand this study may overestimate the risk due to environment, because it looked at hospitalizations, not illness per se. Supposing that poorer people are more likely to get hospitalized, this could mean that the true effect of environment on illness is lower than it appears.
  
• The outcome measure was hospitalization for "non-affective psychosis". Only 40% of this was diagnosed as "schizophrenia". The rest will have been some kind of similar illness which didn't meet the full criteria for schizophrenia (which are quite narrow, in particular, they require >6 months of symptoms).
• Parental bipolar disorder was counted as a family history. This does make sense because we know that bipolar disorder and schizophrenia often occur in the same families (and indeed they can be hard to tell apart, many people are diagnosed with both at different times.)

Overall, though, this is a solid study and confirms that genes and environment are both relevant to psychosis. Unfortunately, almost all of the research money at the moment goes on genes, with studying environmental factors being unfashionable.

Wicks S, Hjern A, & Dalman C (2010). Social Risk or Genetic Liability for Psychosis? A Study of Children Born in Sweden and Reared by Adoptive Parents. The American journal of psychiatry PMID: 20686186