Phenylketonuria and Depression

Phenylketonuria and Depression

Depression can affect anyone, but people with phenylketonuria (PKU) appear to be at a higher risk. Here is more information about how PKU relates to depression, and some possible treatment options.

What is depression?

Depression is long-lasting feelings of sadness, emptiness, worthlessness, or loss. It is a fairly common, and serious mood disorder. It can affect how you think and feel, and disrupt your sleeping, eating, and working habits.

What is PKU?

Mutations in the PAH gene cause PKU. This gene contains the instructions necessary for cells to make an enzyme called phenylalanine hydroxylase. This enzyme helps to convert an amino acid called phenylalanine (Phe) into another amino acid called tyrosine (Tyr). Amino acids are building blocks of proteins.

These mutations result in lower levels of functional phenylalanine hydroxylase enzymes, which causes a buildup of Phe and a lack of Tyr in the body. Nerve cells use Tyr to make neurotransmitters, or chemical messengers, such as dopamine and epinephrine. Tyr’s deficiency in the brain can lead to many of the neurological symptoms of PKU.

How can PKU lead to depression?

Studies have shown that depression is more common in people with PKU than the general population. One study involving 3,714 PKU patients and 22,726 patients without this disease found that 19.5% of those with PKU had depression compared with 11.8% of those without it.

There are a couple of ways that PKU can lead to depression.

Since the brain uses Tyr to make dopamine, low levels of Tyr lead to low levels of dopamine, which research has tied to depression, including major depression.

A study into dietary use of Phe supplements also linked elevated Phe levels with changes in patients’ moods, including greater feelings of depression and fatigue. And it noted earlier work suggesting that, because Phe and Tyr share the same transporter to cross into the brain, high levels of Phe further limit the amount of Tyr — and subsequently dopamine — available to the brain.

Another study in eight young adults with PKU, all on controlled diets, found a “significant correlation” between lifetime Phe levels and mood (anxiety and stress), and linked higher Phe-to-Tyr ratios in the blood with stronger feelings of depression and anxiety.

Another way in which PKU can cause depression is through less direct, psychosocial factors. Knowing you have a chronic illness needing lifelong attention can be overwhelming, and depression is estimated to affect 1 in every 3 people with a chronic disease. PKU patients also have to adhere to a very strict and limited diet, which can lead to feelings of isolation and loss that can turn into depression.

How do doctors treat depression in PKU?

It is important to speak to your doctor if you feel you are struggling with depression. They may be able to prescribe psychotherapy or antidepressant medications, or offer other help.

It is also important that you maintain your special, low-phenylalanine diet. This diet keeps you from absorbing more Phe through food, and supplements Tyr to help balance the levels. Patients with continued high Phe levels despite keeping to their diet may find it helpful to add a treatment that works to lower Phe levels, such as Palynziq or Kuvan.

You should seek immediate assistance if you have feelings of hopelessness or worthlessness, or suicidal thoughts. The National Suicide Prevention Lifeline in the U.S. and the International Association of Suicide Prevention in Europe can help.


Last updated: Oct. 22, 2020


Phenylketonuria News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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