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What Causes Mental Illness? It's Complicated.

I tell my patients, "Mental illnesses are medical illnesses, like diabetes or heart disease." Most of them struggle to believe me because they know that many people, even people who love them, think they can just "get over" their illnesses. And they're equally as hard on themselves. So let's talk about what causes mental illness, and why that question (and answer) are pretty complicated.
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A man wearing a shirt sits in his kitchen looking out of window on a sunny day
A man wearing a shirt sits in his kitchen looking out of window on a sunny day

I tell my patients, "Mental illnesses are medical illnesses, like diabetes or hypertension". "Mental illnesses are inflammatory illnesses, like heart disease or arthritis". "Mental illnesses are brain illnesses that can become chronic and progressive, like Parkinson's Disease". Unfortunately, most struggle to believe me because they know that many people, even people who love them, think, "If she'd just (...try harder, exercise more, eat better, take vitamin C...) she'd get better". Patients are even harder on themselves.

What causes their mental illness? Why them and not someone else? All mental illnesses have "biopsychosocial" origins. "Bio" refers to the biological aspects of these illnesses, such as genetics, brain circuits, hormones, and neurotransmitters. "Psycho" stands for psychological and can include personality style, innate resilience/ vulnerability or the ability to use cognitive skills to manage stress. "Social" refers to life circumstances that impact feelings and function, like financial hardship, the death of a loved-one or legal difficulties.

Mental illnesses often run in families. Children born into families with a history of highly genetic mental illnesses, like bipolar disorder, ADHD, and schizophrenia, have a vulnerability to the illness in every cell of their body, embedded in their DNA.

I think of DNA as being like a piano, but everyone has their own unique keyboard (except identical twins -- they have identical keyboards). We get 50% of our DNA from mom and 50% from dad, and every cell in our body has exactly the same DNA.

If every cell has the same DNA, what causes one cell to become a brain cell and another to become a heart cell or a liver cell? This happens because every key on our own, unique piano keyboard represents a section of DNA called a gene. Genes hold the information needed for cellular differentiation, so when specific genes are turned on (expressed) or turned off (suppressed) they direct what a cell will become. Certain genes hold the code for traits like eye color or height, and other genes direct cells to become heart muscle or skin cells. If our DND is like a piano keyboard, the way the keys are played (the way genes are expressed) makes you who you are. Think of it as "your song" or "the music of you".

We now know that life events and our environment can affect how genes are expressed. An example of our environment impacting gene expression is when the toxins associated with cigarette smoke trigger the expression of cancer-causing genes or the suppression of genes that protect against cancer. Just like cigarette toxins can cause cancer, there is growing evidence that certain environmental exposures or life stressors can alter gene expression and provoke mental illness.

No mental illness is 100% biological. Even for highly genetic illnesses like schizophrenia, if one identical twin has the illness, the other twin has only a 50% risk of also developing schizophrenia, despite having identical DNA. We haven't figured out precisely which genes are responsible for mental illnesses, but scientists have identified many "candidate genes" that are likely involved.

Gene-environmental interactions that might trigger the development of schizophrenia include infections during pregnancy, abnormal bowel flora (microbes that live in the gut), and smoking cannabis. These and likely other environmental exposures are of greatest concern in vulnerable individuals, like those who have a family history of the disorder.

Depression exemplifies the "biopsychosocial" model because it has a genetic basis in many families, but psychosocial factors are also extremely important in the development and persistence of depression. Severe stress is not necessary to develop depression, but it's common for the first episode of depression to follow a stressful life event. However, subsequent depressive episodes may be provoked by little or no stress.

Stress prompts the brain's "stress response command center" (the hypothalamic-pituitary axis) to release the hormone cortisol, which helps the brain and body respond to stress. However, severe and prolonged stress can result in chronically high levels of cortisol, which can trigger an inflammation response that damages cells in specific brain regions. Those damaged brain cells then provoke even more inflammation.

There is a well-documented reduction in the volume of the hippocampus, a brain region important for memory and emotions, in depressed and anxious patients. If not treated quickly and fully, the brain injury associated with depression can become chronic and less responsive to treatment. With each depressive episode, inflammation can worsen the brain injury, resulting in serious cognitive and functional impairment. This is an example of how something that seems psychological or social, like the stress of a divorce or job termination, can have serious biological consequences.

Not everyone is equally predisposed to mental illness. A family history certainly heightens the risk, but ultimately everyone is vulnerable. Most patients will say they never expected to develop a mental illness. Sadly, the statement, "I can't believe this has happened to me", is often followed by, "I'm so ashamed/ embarrassed/ humiliated this happened to me". I have never heard anyone say that about their arthritis diagnosis.

When two people are exposed to the same level of stress, why does one person become ill and the other does not? It's because every individual has a unique and often complicated "biopsychosocial story". We usually don't know the full story, so it's probably best not to judge, but to encourage and support those struggling with a mental illness, and congratulate them for their bravery for seeking help.

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