It’s not the first time we’ve discussed the effect of genetics on individuals’ mental health in this blog.
The relevance of genetics in mental disorders is undeniable, with varying importance depending on the pathology. It’s not uncommon that when a person presents with such a disorder, upon reviewing their family history, a relative who has also experienced it is found.
They don’t have to be the same. Having a relative with a psychiatric illness increases the risk of developing a range of psychiatric disorders, not only the specific pathology that the family member suffered from.
The closer the relative, the higher the risk. It makes sense since the closer the relative, the more percentage of the genome you have in common.
These disorders are not mutually exclusive. Approximately half of people with a psychiatric disorder develop a second one during their lifetime. As stated in a study, in these cases, comorbidity is the norm rather than the exception.
For your convenience, comorbidity refers to the presence of two or more diseases simultaneously in one person.
Multiple disorders, common genes
The genetics of these pathologies are complex. The most supported hypothesis is that there are a series of genetic risk variants, the vast majority still unknown, that participate in different pathways of the organism. These variants also act indirectly, being part of cellular signaling cascades, which complicates their identification even further.
An international study in 2013 sought to prove something. They knew that autism, attention-deficit hyperactivity disorder (ADHD), bipolar disorder, major depression, and schizophrenia can present common symptoms. This poses a problem because it complicates diagnosis.
So, they asked themselves, what if, in addition, they present common genetic alterations? To check this, they analyzed genetic variations in 33,000 individuals who had at least one of these disorders. On the other hand, 28,000 control individuals, who were not diagnosed with any psychiatric problem.
Among the alterations that appeared with suspicious frequency among people affected by disorders, variations in two genes were statistically significant: CACNA1C and CACNB2.
- CACNA1C is involved in the formation of voltage-dependent calcium channels in cells and in the entry of calcium into the cytoplasm.
- CACNB2 also participates in voltage-dependent calcium channels, increasing their current.
Finding that both genes shared very similar functions reinforced the importance of calcium transport in the central nervous system.
Other biochemical pathways in the brain that are often found altered in mental disorders are those related to energy metabolism and mitochondrial function. If we consider that mitochondria participate in the regulation of cytosolic calcium and accumulate it inside, it makes special sense.
Some studies focused on these pathways have confirmed their abnormal functioning in psychiatric disorders, especially in autism and schizophrenia.
When reading this, a natural question that may arise is: if these diseases share so many genetic variants, why are they different from each other, even though they share some symptoms?
Similar but distinct mental disorders
The most accepted proposal is the simplest one: even if they share common genetic variants, their altered expression occurs in different cells and regions of the brain. For example, in bipolar disorder, the paraventricular nucleus of the thalamus is often affected, while in depression, the dorsal nucleus of the raphe is more commonly involved. These are areas of the brain with very impressive names, but we would be unable to locate them on a brain map.
One detail to consider; just as there are genetic variants that are frequently common among these disorders, the same occurs with some brain regions. The CA1 region of the hippocampus is a region affected in many of these patients, regardless of the pathology.
Another genetic detail to consider is to think about the opposite case: the relevance of genes involved in these disorders that are not common among patients.
A study of autism spectrum disorder (which has high heritability) conducted in more than 18,000 patients wanted to see, not so much the common variants, but rather those that were different among subjects.
Within this disorder, there are different subclasses with significant differences between them. And the results coincided: among the patients, there was also a great polygenic heterogeneity. Even in the heritability of the disorder.
The categories of autism that involved intellectual disability had the lowest heritability. This was because it was caused by de novo mutations, which did not come from the family.
It is important to mention that they found that common variants were precisely among those with less weight in the patient. Individual variants, unique to a few, had a greater effect on the individual’s condition.
The interesting thing about all this is that not only are there genetic variants that are common within a mental disorder, but also those unique variants of each patient are decisive in the expression of the pathology and dictate the different subclasses.
Perhaps one of the most curious examples is bipolar disorder. Among others, there are the so-called bipolar disorder I and II, which, although classified within the same classification, have different diagnoses. Bipolar disorder I has a greater genetic association (more quantity of common genetic markers) with schizophrenia, while bipolar disorder II with major depression.
In 2023, in one of the largest studies on ADHD (38,691 patients), the aforementioned conditions were met. Researchers calculated that 84-98% of the variants influencing ADHD were shared with other psychiatric disorders. But genetic risk was associated with special relevance to specific neuronal subtypes of the brain, such as dopaminergic neurons in the midbrain region. Same variants, different cells.
However, it is impossible to overlook environmental conditions in these diseases. They are classified into three groups: physical, social, and other factors.
Among the environmental factors that can trigger the disease are stress, brain inflammation, diet, infections, or the presence of toxins (this would include drugs that the individual consumes voluntarily).
The human mind is so complex that even it struggles to uncover its secrets. Fortunately, human genetics are a little less complex, and we have the tellmeGen Advanced DNA Kit.
