How Does Phenylketonuria Affect Mood?

How Does Phenylketonuria Affect Mood?

People with phenylketonuria (PKU) have increased rates of mood disorders such as depression and anxiety. Here are some things to consider about how PKU can affect mood and some things you can do to improve it.

What is PKU?

PKU is a genetic disorder that results in high levels of the amino acid phenylalanine (Phe) in the body. This is due to problems with the metabolism or breakdown of Phe into another amino acid, tyrosine (Tyr). The buildup of Phe and subsequent lack of Tyr lead to symptoms that include neurological, developmental, and skin problems.

How does PKU affect mood?

The disorder can result in the decrease in several neurotransmitters or cell signaling molecules in the brain, including dopamine, serotonin, and norepinephrine. While those decreases occur through several different mechanisms, the end result is the same: they can lead to mood and psychiatric and cognitive disorders. 

A small, randomized study in people with PKU showed an association between high levels of Phe in the blood and a worsening in mood. Specifically, the patients reported an increase in depression and fatigue, and a lack of vigor during the periods when they had increased Phe in their blood. Friends and relatives also reported increases in the patients’ depression and fatigue, as well as worsening anger levels during the high Phe period. 

Psychosocial factors also can lead to changes in mood for individuals with PKU. Patients may feel isolated from their peers because they have a rare disease and because they have to adhere to a special restrictive diet

How can mood be improved?


Research has shown that maintaining a diet low in Phe with other protein supplements throughout a patient’s life can help mitigate symptoms of PKU. Diets higher in Phe may have an association with increases in feelings of depression and anger. Thus, limiting exposure to dietary Phe can help improve mood in PKU.


Other factors besides diet can affect mood as well. If you or your child have depression or anxiety, it may be helpful to seek counseling services. Cognitive behavioral therapy (CBT), a common type of talk therapy, can help in dealing with feelings such as stress and depression.


Lifestyle changes such as exercising can improve mood. Getting adequate and restful sleep also can ease mood problems as can increasing exposure to sunlight through the regulation of serotonin and melatonin. However, it is important not to overdo it as the skin of PKU patients may already be fragile. 


You should discuss any problems with negative mood with your physician or healthcare team. They may be able to recommend other treatments or medications, which could help reduce feelings of depression or anxiety.


Last updated: Sept. 10, 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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