It’s the Genes Stupid: Depression, Autism, and Antisocial Behavior
The nature versus nurture debate has been going on for decades. Ask a psychologist whether a problem is nature or nurture and she/he will inevitably say “It’s both!” However, as research becomes increasingly sophisticated, we can examine more specific questions. How do genes and biology impact mental health symptoms? At what ages are people more or less influenced by environmental influences? Are genetics related to different disorder subtypes? As you can see there are many different questions that need to be answered to help with diagnosis and treatment, some of which researchers have already started to look at.
This post provides an overview of how genes are or are not related to mental health. Specifically, depression, autism, and antisocial behavior are examined as an illustration of the variety of ways genetics are related to behavioral and emotional functioning. However, this article could have easily also been about how genetics influence posttraumatic stress disorder, obsessive compulsive disorder, schizophrenia, or anxiety. Unfortunately, there is not enough time to talk about ALL THE THINGS, so here we are. Let us get started with a brief introduction about why we are talking about genetics in the first place.
There has been a big push in research to determine how genetics are related to illnesses, both physical and mental. For example, research done with cancer has found that different genotypes (i.e., your specific genetic makeup) respond better to different interventions. The same concept is being used for mental health problems as well. Theoretically, if we can identify which genes are related to mental health problems such as depression, we can better understand why depression occurs. The dream would then be to identify a “depression gene” so that people with that gene could be targeted for interventions that prevent or effectively treat the problem. Sounds promising right?
Unfortunately, research in this area has not panned out to be as easy or straightforward as it was originally hoped for. It turns out that the genetic contributions for mental health conditions such as depression, autism, and antisocial behavior are incredibly complex. Instead of looking for one or two gene locations that predict depression, researchers are finding that thousands of gene locations are related to depression. Let us take a quick look at what some of the genetic research on depression has found.
Depression is a mood disorder characterized by a variety of symptoms including: feeling sad, hopeless, or empty, experiencing changes with regard to appetite, weight, and/or sleep, feeling worthless, or having difficulty concentrating. Depression is one of the most common mental health disorders and an estimated 16 million adults in the United States experienced depression in 2015 and an estimated 300 million people worldwide experience depression. In addition, depression is one of the highest causes of disability around the world, which highlights the importance of being able to prevent and treat depression.
Looking at genetic research on depression, probably the most commonly studied gene is what is called the serotonin transporter linked polymorphic region (5-HTTLPR). Broadly, serotonin is a neurotransmitter that is believed to be important in the development and maintenance of depression. It makes sense then that one of the frontline psychiatric interventions for depression is often a selective serotonin reuptake inhibitor (SSRI) such as Zoloft, Lexapro, or Prozac.
A meta-analysis of 14 studies looked at how the 5-HTTLPR genotype and stressful life events are related to depression; over 14,000 people were a part of these 14 studies, including almost 1800 individuals with depression (Risch et al., 2009). What this study found was that the number of stressful events an individual experiences is related to depression. However, there was surprisingly no evidence that the 5-HTTLPR genotype is related to depression, either on its own or when examined with stressful events at the same time. This was also true when the analyses were done with males, females, and combined groups.
A review of the literature of studies examining the ways genetics are related to depression by Flint and Kendler (2014) notes that over 200 candidate genes (such as 5-HTTLPR) have been examined by researchers, and 26 of these genes have had meta-analyses conducted to examine overall effects, like the Risch and colleagues (2009) study. According to Flint and Kendler, none of the meta-analyses show convincing evidence of the influence of any particular candidate gene and studies that have looked at these genes are typically underpowered statistically and likely have high false-positive rates for findings (i.e., saying a relationship exists when in reality it does not).
And so again there has been little support for these candidate genes being related to depression. This is perhaps not surprising as studies that have looked at the whole genome (called genome-wide association studies) have also not found significant effects related to depression.
However, this does not mean that genetics are unrelated to depression. Indeed family studies have found that the heritability estimate of depression is 37%. Put differently, depression is over a third due to genetics and less than two-thirds due to environmental influences.
An alternative explanation is that there are not one or two genes that lead to depression, but instead thousands of specific areas on genes that each contribute small effects towards the development of depression. This would help explain why it has been so hard to find precisely how genetics are related to depression.
Briefly, other interesting findings summarized in Flint and Kendler (2014) include that depression and anxiety are due to the same genetic contributions, that is to say there is no difference between these two mental health problems genetically. In addition, depression appears to have some genetic overlap with bipolar disorder (which is essentially when a person experiences depression and at least one episode of mania), although depression also appears to have unique genetic influencers compared to bipolar disorder.
Now let us turn our attention to a neurodevelopmental disorder, known commonly as autism.
Autism spectrum disorder (ASD) is the umbrella term that is now used to classify individuals who were previously diagnosed with conditions including autistic disorder, Asperger’s disorder, and pervasive developmental disorder - not otherwise specified (PDD-NOS). Individuals with autism can widely vary in terms of presentation; some individuals are high functioning and have productive, happy lives, whereas other individuals are low functioning and may be nonverbal and require significant support for daily functioning.
There has been a lot of attention paid to the causes of autism. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classifies ASD as a neurodevelopmental disorder. The neurodevelopmental disorders section is composed of conditions that occur early in development and have strong biological influences.
Given the strong biological influences on autism (and no it is not due to vaccines), researchers have attempted to understand the genetic contributions to this disorder. Similar to depression, ASD is a complex phenomenon that does not have a single genetic cause. Indeed, no single genetic mutation, syndrome, etc. accounts for more than 1-2% of autism cases.
Despite this being the case, genetics appear to be the strongest factor related to ASD (Abrahams & Geschwind, 2008). For example, there is a 70-90% chance for an identical twin to have ASD if his or her twin has ASD, compared to a 0-10% chance for fraternal twins. In addition, ASD is two to five times more likely to be diagnosed among boys compared to girls, suggesting some biological processes are at play.
It also appears that genetic contributions to ASD depend on which symptom categories are being examined. ASD is characterized by deficits in social communication as well as restricted, repetitive patterns of behavior and interests. Research indicates that unique genetic factors are related to the deficits in social communication compared to genetic factors related to restricted, repetitive behaviors and interests (Freitag, 2007).
There are different neurobiological hypotheses as to how genetics are related to autism (Freitag, 2007). One hypothesis is that there are broad dysfunctions with how the cells in the brain (neurons) talk to each other. However, it is hard to understand how these broad dysfunctions are related to ASD behaviors and sometimes not intellectual deficits. Other hypotheses are that there are deficits with mirror neurons (which allow us to feel emotions we see other people experience). Lastly, brain areas involved with joint attention (when two people focus on the same thing) may be important, as joint attention is critical for both understanding social behaviors and learning language, both of which can be deficits for individuals with ASD.
Last, genetics research on antisocial behavior will be examined.
Antisocial behavior is a term used to cover a wide set of acts such as physical aggression towards others, lying, stealing, and other unlawful behaviors. There is a strong interest in finding out the causes of antisocial behavior because as a society we pay a shocking $274 billion each year to fund the criminal justice system. Indeed, it is particularly an issue in America where we incarcerate 20% of the world’s prisoners despite only have 5% of the world’s population.
Understanding the causes of antisocial behavior is important as it will allow us to most effectively target interventions and identify individuals most at risk for antisocial behavior.
A review of the literature overall finds that about half of the variance in antisocial behavior can be attributed to genetics (Ferguson, 2010), meaning genetics explains about half of antisocial behavior that occurs. This review further states that approximately 11% of the variance in antisocial behavior is due to shared non-genetic influences (e.g., living in the same high-conflict home or dangerous neighborhood) and 31% of the variance is due to unique non-genetic influences (e.g., having poor coping strategies or antisocial friends).
The gene that has received the most attention in the literature related to antisocial behavior is the monoamine oxidase A (MAOA) gene which is found on the X chromosome. This MAOA gene was given the dubious nickname of the “warrior gene” and was found in 1993 from genetic testing done with a large Dutch family well known for violence. Other research done in New Zealand by Caspi and colleagues have shown that the combination of a variant of this MAOA gene and the exposure to family violence together increases the risk of aggression and violence in children, which can then carry on into adulthood.
Overall, it does not appear that variants of the MAOA gene on their own are strong predictors of antisocial behavior and that MAOA is more consistently associated with antisocial behavior when there are other stressors, whether that is negative peers, financial stress, or neuropsychological deficits (Gunter et al., 2010).
Another gene that has gotten attention in the literature is the serotonin transporter promoter gene (5-HTT), which was also discussed when we talked about depression. Broadly the literature appears to connect 5-HTTLPR with ADHD and aggression, although not every study found this association and not every individual with ADHD is aggressive (Gunter et al., 2010). The connection here is instead that individuals with ADHD can often be impulsive, and this impulsivity is also a risk factor for aggression. Similar to the MAOA gene, 5-HTTLPR appears to be more consistently related to antisocial behavior when environmental stressors are also present.
As previously mentioned, SSRIs are typically used to treat depression. Interestingly, more recently studies have been using these same SSRIs to treat aggression, which makes logical sense given both depression and aggression appear to be related to the 5-HTT gene.
Again, similar to depression and ASD, no single gene determines whether a person engages in antisocial behavior and it instead appears that the genes interact with each other and likely the environment to predict antisocial behavior.
To Sum It Up
At this point, it is clear that genetics are influential in variety of conditions and problems such as depression, autism, and antisocial behavior. However, debate continues regarding how exactly genetics impact psychological processes. Increasingly, it is becoming apparent that to understand complex conditions such as depression and autism, research is going to have to look at complex interactions between genes and the environment that change over time. It is still very much an exciting area of research as there is a lot of area for growth. It seems that the future of genetics research will also be looking at more specific features of conditions, such as repetitive behaviors found with autism, and connecting these features to specific genetic factors.
While genetics play a part in depression, autism, and antisocial behavior, there are also great interventions that target each issue. Cognitive-behavioral therapies, social skills training, and medication can help individuals who are struggling to live happier and healthier lives. In the future, I hope to see genetics research correspond to real-life interventions that help those in need; thus far this body of research has not greatly informed practical interventions and it will be fascinating to see how genetics research can better inform psychological treatment.
The Clinically Relevant Insights Blog, part of ShawnWilsonPhD.com, shares news and research related to psychology and wellness.
Abrahams, B. S., & Geschwind, D. H. (2008). Advances in autism genetics: On the threshold of a new neurobiology. Nature Reviews Genetics, 9(5), 341-355. doi:10.1038/nrg2346
Ferguson, C. J. (2010). Genetic contributions to antisocial personality and behavior: A meta-analytic review from an evolutionary perspective. The Journal of Social Psychology, 150(2), 160-180. doi:10.1080/00224540903366503
Flint, J., & Kendler, K. (2014). The Genetics of Major Depression. Neuron, 81(5), 484-503. doi:10.1016/j.neuron.2014.02.033
Freitag, C. M. (2007). The genetics of autistic disorders and its clinical relevance: A review of the literature. Molecular Psychiatry,12(1), 2-22. doi:10.1038/sj.mp.4001896
Gunter, T. D., Vaughn, M. G., & Philibert, R. A. (2010). Behavioral genetics in antisocial spectrum disorders and psychopathy: A review of the recent literature. Behavioral Sciences & the Law, 28(2), 148-173. doi:10.1002/bsl.923
Risch, N., Herrell, R., Lehner, T., Liang, K., Eaves, L., Hoh, J., . . . Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. JAMA, 301(23), 2462-2471. doi:10.1001/jama.2009.878
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