Probably many of us living with mental illness have wondered at some point where the heck it came from. Nature? Nurture? A hodgepodge of both? Heredity, i.e. what we get from our genes, often seems to play at least some role, but genes aren’t the only game in town. This post looks at what some of the different players are.
Genes and heredity
Our genetic makeup is determined at the time of conception by the genetic content of the sperm and the egg that we’re made from. We normally have 23 chromosome pairs, and one of these 23 pairs is the sex chromosomes, with an X chromosome from the mother and either an X or a Y from the father. Each chromosome is made up of between 200-2000 genes. Genes are made up of DNA and provide the code for our cells to make proteins. The normal state of DNA, when there’s no code-reading action going on, is a double helix configuration. The rungs of the helix are made up of bonds between bases, known for short as A, C, G, and T. This sequence of bases codes for amino acids, which are the building blocks of proteins.
Once you’ve got them, your genes generally aren’t changing much, although spending too much time in the Chernobyl exclusion zone can certainly throw a monkey wrench in things.
Our DNA is wrapped up nice and cozy in proteins called histones. When a section of DNA is needed to do its thing, the histones in that section open up so the code can be read, kind of like a barcode, to make the corresponding RNA. This RNA is then used to make proteins. Epigenetics refers to the way that genes are accessed and used, or not accessed/used, to make the proteins that they code for.
Epigenetic changes can be inherited, but they can also occur as a result of environmental factors (childhood trauma is a big one). This means that unlike genetics, which are mostly consistent through the lifespan, epigenetic changes can happen over time. This could potentially create additive risk for the development of some form of disorder on top of whatever baseline risk you might have from what your DNA code contains.
Heritability refers to how big a factor the genes (i.e. DNA) you inherit are in you developing an illness or other condition. Twin studies are the most common way of estimating heritability. Identical (monozygotic) twins share exactly the same genetic makeup. Fraternal (dizygotic) twins have different genetic makeups, much like siblings who weren’t born twins, but they share the same in utero environment and exposures. The more heritable a condition is, the greater the difference will be in the pairs of identical twins with the disorder compared to pairs of fraternal twins.
Sometimes a single genetic mutation will automatically produce either a disorder or a very high risk for a disorder. Examples of single mutations that can significantly elevate risk are particular variants of the BRCA-1 and BRCA-2 genes, which significantly increase the risk of breast cancer. Huntingdon’s disease involves a mutation in a single gene that is inherited from one parent (referred to as autosomal dominant), while cystic fibrosis involves one gene but there have to be copies from both parents for the condition to occur (autosomal recessive).
Mental illness isn’t like that. A 2009 study found thousands of genetic variants that could contribute to the likelihood of developing schizophrenia. Given the complexity of the whole shebang, science hasn’t got it all figured out quite yet.
One thing that’s really interesting is that having a family history of a mental disorder increases your chance of having a mental disorder across the board. It doesn’t necessarily have to be the same disorder, or even a similar disorder. This cross-over of genetic risk is seen in particular with schizophrenia, autism, bipolar disorder, major depression, ADHD, and anxiety disorders. It’s also interesting that non-psychiatric neurological disorders don’t have that same kind of shared risk.
The overlapping mental illness risk suggests that the categories that the DSM diagnostic manual uses for disorders don’t correspond to what’s going on in the brain. Then again, the DSM never claimed to do that; it describes symptoms and groups like symptom presentations together. It includes information about what studies have indicated about heritability, but it makes no attempt to say why or how an illness happens biologically.
Genetic factors can account for different percentages of the overall risk. Huntingdon’s disease is all genetic. Among mental illnesses, schizophrenia, bipolar disorder, ADHD, and autism spectrum disorder have the strongest genetic contribution, accounting for around 80% of the overall vulnerability. For major depressive disorder, genetics account for about 30% of the overall risk.
If heredity only accounts for part of the risk, where does the rest of the vulnerability come from? That’s where the environment comes in, but not just in terms of nurture.
Our genetic makeup is set at the time of conception, but for the next nine months, everything that happened to our mom happened to us too. That can influence our risk of developing a condition later on. There are indications that maternal infection in the first trimester increases the risk of the child developing schizophrenia as an adult.
There are also epigenetic changes that may occur as a result of conditions we’re exposed to, which bridges nurture and biology. Then there are all kinds of psychosocial factors.
A diathesis-stress model conceptualizes illness as occurring when the combined effects of vulnerability and environmental stress reach a certain threshold. The higher the pre-existing vulnerability, the lower the amount of environmental stress that it takes to push someone over the threshold into illness territory. Regardless of the relative roles that different factors play, the idea of a single root cause for mental illness seems pretty unlikely.
Still a long way to go
I find the cross-over heritability really interesting. I have a family history of schizophrenia but not depression, which I’d thought was kind of odd, but I guess it’s not actually odd after all. All in all, it sounds like there’s a whole lot that that science hasn’t figured out yet. Perhaps at some point, things will get narrowed down to the point where new and more effective treatment options can be identified.
How much of an impact do you think heredity may have had for you?
- Anttila, V., Bulik-Sullivan, B., Finucane, H. K., et al. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395).
- Nature (May 5, 2020): The hidden links between mental disorders
- Pettersson, E., Lichtenstein, P., Larsson, H., et al. (2019). Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls. Psychological medicine, 49(7), 1166-1173.