Fortunately, we’ve come a long way since the theory that less-than-affectionate mothers cause schizophrenia. Today, it’s widely accepted that a complex interplay of genes and environment contributes to schizophrenia, which affects about one percent of the population and is characterized by cognitive dysfunction, delusions and hallucinations.
Researchers have made significant strides in teasing apart schizophrenia’s convoluted genetic vulnerabilities, but there’s still a slew of questions. Even with sophisticated technology, researchers are still left scratching their heads about the specifics: what genes are involved, how they incur risk, whether certain mutations link to the different subtypes and so on. Below is a discussion of how genetic research has evolved and what we know today.
Early Research: Family, Twin & Adoption Studies
To determine whether genetics plays any role in schizophrenia, decades ago, researchers began by looking at the prevalence of the disorder in families along with fraternal and identical twins. As many already know, these studies showed that schizophrenia runs in families and has a high heritability rate among identical twins, upward of 80 percent.
What does heritability mean exactly? According to Anna Need, Ph.D, schizophrenia researcher and assistant professor in the Center for Human Genome Variation at Duke University, it tells us that in those particular studies, roughly 80 percent of the variance can be explained by genetics.
Adoption studies are another avenue for answers. This research revealed that kids whose biological parents are schizophrenic (whether the onset was before or after the adoption) were at an elevated risk for psychosis. But kids adopted into families where one of the adoptive parents has schizophrenia were not at an increased risk for developing schizophrenia.
Linkage studies explore regions of chromosomes within large families affected by schizophrenia and compare these families to those untouched by the disorder. According to Need, “although some loci have more evidence than others, no chromosomal region has been consistently implicated through linkage studies.” Researchers have either reported different results or others have refuted their findings.
Part of the problem may be that linkage studies typically combine families because families affected by schizophrenia usually don’t have many members. This may confound results, Need said, because it may be that there are “strong [genetic] contributors but they’re different in different families, [so] when you try to combine different studies, they don’t replicate.”
Two fairly recent genome scan meta-analyses did find some significance on several chromosomes. One meta-analysis, which looked at 20 different genome-wide datasets, identified a region on chromosome 2q. The second meta-analysis of 32 studies confirmed a region on chromosome 2q and also on chromosome 5q. These researchers conducted another analysis on 22 studies with samples of European descent and found potential linkage on chromosome 8q. Still, these chromosome regions are very large and have hundreds of genes.
“What we know for sure is there isn’t one or a few causes. That’s all we can say for linkage studies,” Need said.
Candidate Gene Studies
In candidate gene studies, “researchers select individual genes that make sense biologically, or because they are in linkage regions, or both,” Need said. Then they look for differences in the frequency of different variants in people with schizophrenia and without.
However, “these types of studies can be confounded by population differences between cases and controls, small sample size and positive publication bias. Few if any of the hundreds of genes implicated in candidate gene studies are likely to have real effects.”