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March 29, 2024

Understanding the many complex causes behind mental disorders

By ALYSSA WOODEN | November 29, 2018

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The question of what causes mental illnesses and disorders has been debated by doctors, researchers and psychologists for decades.

One of the most widely-accepted approaches to understanding the causes of mental illness is the biological approach. This is the assumption that mental illness is due to defective biological mechanisms, such as neural circuitry and biochemistry. Depression, for example, is thought to result from a deficiency in serotonin. Serotonin is a neurotransmitter, a chemical that passes between synapses in the brain, and is responsible for feelings of well-being and happiness. Today most prescription medications for depression are selective serotonin reuptake inhibitors (SSRIs), which block reabsorption of serotonin, thereby increasing its amount in the brain.

Similarly, psychotic disorders such as schizophrenia have been linked to abnormal release of dopamine, which regulates the brain’s reward center. Antipsychotics work by blocking dopamine receptors.

However, neither antidepressants nor antipsychotics have been successful in treating the full range of symptoms related to their respective mental illnesses, suggesting that there may be causes other than chemical imbalances. Researchers currently believe that depression and similar disorders are caused by a combination of genetics, psychological trauma, environmental stressors and chance combinations of personality traits.

Studies have shown that the risk of acquiring a mental illness increases if a family member has been diagnosed, indicating that there is a genetic component to mental illness. Although the stress of living with someone with a mental disorder may partially account for this risk, these findings have been replicated in adoption studies. For example, the prevalence of schizophrenia is significantly greater in individuals who have biological relatives with schizophrenia than in those who were adopted by people with the disorder. 

Genes that code for proteins that regulate neurodevelopment may contain variations that alter the function of neural circuitry, resulting in mental illness. These dysfunctional genes can be passed on, leading to higher risk of illness in future generations.

Dr. James B. Potash, a researcher at the School of Medicine’s Mood Disorders Center, is part of a team that has identified over 40 genetic variations for bipolar disorder, as well as a comparable number of variations for depression. He explained that genetics is only one of many factors contributing to psychiatric disorders.

“It’s not the case that you have a genetic variant and you will inevitably get the disease,” Potash said. “Instead what it looks like is that combinations of genetic variations seem to increase the likelihood that you can get the illness, but it’s by no means deterministic.”

He elaborated that environmental factors such as stress can play an important role.

“The thing that’s pretty clear cut certainly with depression is that major stressful life events increase the risk of depression,” he said. “We think that these major stressors interact with genetic variation in some way possibly through a mechanism of epigenetics.”

Epigenetics is the study of factors that change gene activity without changing the DNA sequence itself. One example is DNA methylation, which occurs when methyl groups are added to DNA. These changes are reversible and are not necessarily passed down to offspring.

Specific epigenetic differences have been found in the brains of people affected with schizophrenia, bipolar disorder and major depressive disorder. Because the brains of suicide victims with depression who had suffered abuse had higher methylation rates than the brains of those who had not suffered abuse, researchers have determined that this epigenetic response is triggered by environmental stressors. This suggests that environmental factors like stress or trauma also contribute to genetic disorders.

These findings have been replicated in animal studies. One study found higher rates of methylation of a gene associated with stress response in rats who received high levels of maternal care than in rats who received lower levels of care. The adult offspring of the high-level-maternal-care rats were less fearful and had more modest responses to stress than the rats raised by less caring mothers.

Notably, this methylation was reversible; when researchers removed the methylation in low-level-maternal-care rats, their stress response returned to normal. 

Despite the extensive research, Potash noted that there is no way to definitively prevent depression, although there are things individuals can do to reduce their risk.

“We know that broadly speaking, there’s some things that probably help protect you. Probably a stable sleep schedule helps, not drinking to excess or using illicit drugs probably helps, exercise probably helps,” he said.

In the future, Potash’s findings may advance the field of pharmacogenetics, which involves using genetics to determine an effective course of treatment.

“Pharmacogenetics essentially means looking at genetic variations that might predict who’s going to respond to particular antidepressant medications and who isn’t,” he said. “There’s a lot of talk about that... companies are actually marketing a number of tests to the public, but the data is not strong yet to clarify whether they really work or not.”


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