How Genetics impact Mental Health

Scientists have long recognized that many psychiatric disorders tend to run in families, suggesting potential genetic roots. Twin studies suggests that all major psychiatric disorders have a heritable componentAnxiety disorders, PTSDOCD, and major depressive disorder are about 20-45% inherited, alcohol dependence and anorexia nervosa are 50-60% inherited, whereas bipolar disorderautism spectrum disordersschizophrenia, and ADHD are upwards of 75% inherited.

The chance of an individual having a specific mental disorder is higher if other family members have that same mental disorder. Even though a mental disorder may run in a family, there may be considerable differences in the severity of symptoms among family members. This means that one person in the family may have a mild case, while someone else has a more se​vere case of the mental disorder. Mental disorders, however, do not follow typical patterns of inheritance.


How Genetics impact Mental Health

 

Most mental disorders are caused by a combination of multiple genetic and environmental factors. This is called multifactorial inheritance.

Environmental factors

Environmental factors contributing to the development of mental disorders include:

  • Trauma: Sexual, physical, and emotional abuse during childhood all lead to an increase in the likelihood of developing a mental disorder. Highly stressful home environments, loss of a loved one, and natural disasters are also major contributors. 
  • Emotional harm: Negative school experiences and bullying can also result in severe long-term emotional damage. The realization of these issues has led to anti-bullying campaigns nationwide, and the implementation of these campaigns has placed a larger importance on the overall mental health of school-aged children and teens.
  • Substance Abuse:Exposure tobacco, alcohol, and illicit drugs either prenatally or in childhood has been associated with the development of mental disorders beyond just substance use disorders or addiction

Environmental factors alone do not cause mental disorders. Genetic factors also play a part in developing a mental disorder. 

Genetic factors 

Genetic factors contributing to the development of mental disorders include:

  • Epigenetic regulation:Epigenetics affect how a person reacts to environmental factors and may affect whether that person develops a mental disorder as a result. Epigenetics is not constant over time. This means a gene is not always “on” or “off.” There must be the right combination of environmental factors and epigenetic regulation for a mental disorder to develop. 
  • Genetic polymorphisms:These changes in our DNA make us unique as individuals.A polymorphism alone will not lead to the development of a mental disorder. However, the combination of one or more specific polymorphisms and certain environmental factors may lead to the development of a mental disorder.  
  • Single gene changes: Rare.

So while we know quite a few things, the question arises, why haven’t we found all the associated genes and contributing factors?

  • The human genome project finished its work in 2003. Scientists started focusing on SNPs (or small sections of DNA) that are common after that. All of these disorders are polygenic (there is definitely not any one gene that causes depression or schizophrenia, in other words: multiple genes add or subtract from your risk instead), and while most are related to common SNPs (carried by more than 1% of the population), many weren’t in the first SNPs characterized that were looked at in large GWAS (genome-wide association studies) trying to help us understand the heritability of mental illness.
  • In year 2007, we had the huge sample sizes to look at all the different SNPs in any meaningful way, and not until a few years after that it was possible to do it less expensively.
  • The risk variants for psychiatric disorder, when discussed in terms of SNPs, could number in the thousands, spread across the entire genome. In addition, there are some genetic disorders (one of the most famous being Huntington’s disease) that come from repeated copies of a certain piece of DNA, or, alternatively, rare deletions. Families with high rates of autism spectrum disorders, ADHD, and schizophrenia have all been found to have rare genetic copy number variations that likely predisposed these families to the risk of these disorders.

Interestingly in schizophrenia, scientists found that a functional variation of complement (inflammatory immune protein) genes correlated with a strong signal for increased risk of schizophrenia. Turns out these risk alleles have an impact on the pruning of neurons in the inflammatory system of the brain. Here’s a situation where the genetic findings line up with the known pathology of the disorder, a type of inflammation that interferes with brain development at a critical period (typically late adolescence to early adulthood). These findings could help us predict and perhaps even prevent the disease, if we know enough and can intervene early.

Psychiatric genetic research is still in early days and given all the work and light put by current COVID-19 pandemic on Mental Health, the future looks promising. We are sure Doctors and other clinicians will keep us informed in following the rapid progress of the research and how it may help drive positive outcomes for people battling with Mental Health conditions.

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