Health Conditions Related to Genetic Changes 22q11.2 deletion syndrome The characteristic signs and symptoms of 22q11.2 deletion syndrome result from a deletion of a small piece of chromosome 22. The chromosomal region that is typically deleted contains 30 to 40 genes, including the COMT gene. As a result of the deletion, people with this disorder have only one copy of the COMT gene in each cell instead of the usual two copies.
A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain. Researchers believe that changes involving this enzyme in the prefrontal cortex may help explain the increased risk of behavioral problems and mental illness associated with 22q11.2 deletion syndrome. Little is known, however, about the relationship between catechol-O-methyltransferase activity and the specific mental and emotional problems characteristic of this condition. People with 22q11.2 deletion syndrome are much more likely than people without the condition to develop schizophrenia, depression, anxiety, and bipolar disorder.
Alcohol use disorder
Fibromyalgia
Fibromyalgia is a common condition characterized by long-lasting (chronic) pain affecting many areas of the body. The pain is associated with tenderness that occurs with touch or pressure on the muscles, joints, or skin. Some affected individuals also report numbness, tingling, or a burning sensation (paresthesia) in the arms and legs.
Other signs and symptoms of fibromyalgia include excessive tiredness (exhaustion); sleep problems, such as waking up feeling unrefreshed; and problems with memory or thinking clearly. People with fibromyalgia often report additional types of pain, including headaches, back and neck pain, sore throat, pain or clicking in the jaw (temporomandibular joint dysfunction), and stomach pain or digestive disorders such as irritable bowel syndrome. They have an increased likelihood of developing mood or psychiatric disorders including depression, anxiety, and obsessive-compulsive disorder. However, many people with fibromyalgia do not have a mental health condition.
The major signs and symptoms of fibromyalgia can occur by themselves or together with another chronic pain condition such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or systemic lupus erythematosus.
Opioid addiction
Opioid addiction is a long-lasting (chronic) disease that can cause major health, social, and economic problems. Opioids are a class of drugs that act in the nervous system to produce feelings of pleasure and pain relief. Some opioids are legally prescribed by healthcare providers to manage severe and chronic pain. Commonly prescribed opioids include oxycodone, fentanyl, buprenorphine, methadone, oxymorphone, hydrocodone, codeine, and morphine. Some other opioids, such as heroin, are illegal drugs of abuse.
Opioid addiction is characterized by a powerful, compulsive urge to use opioid drugs, even when they are no longer required medically. Opioids have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed. Many prescription opioids are misused or diverted to others. Individuals who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively impacting their professional and personal relationships. It is unknown why some people are more likely to become addicted than others.
Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect. Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction.
Opioid addiction can cause life-threatening health problems, including the risk of overdose. Overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines).
Schizophrenia
Other disorders Variations in the COMT gene also may be associated with mental illness in people without 22q11.2 deletion syndrome. Researchers have looked extensively at the potential connection between changes in the COMT gene and the risk of developing schizophrenia. Most studies have focused on the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase. This variation alters a single protein building block (amino acid) in the enzyme, replacing the amino acid valine with the amino acid methionine. In the longer form of the enzyme, this variation occurs at position 158 (written as Val158Met). In the shorter form of the enzyme, it occurs at position 108 (written as Val108Met). Researchers often shorten this notation to Val108/158Met. The change affects the stability and activity of catechol-O-methyltransferase, which alters the enzyme's ability to break down neurotransmitters in the prefrontal cortex.
Studies of the Val108/158Met polymorphism in people with schizophrenia have had mixed results. While most studies report no evidence of heightened risk with either methionine or valine at this position, some studies have found a slightly increased risk of schizophrenia in people with valine at position 108/158. Having valine at this position is associated with differences in thought processes that are common in people with schizophrenia, including problems with working memory, inhibition of behavior, and attention. Other changes in the COMT gene may also contribute to these differences. Variations in the COMT gene are among many factors under study to help explain the causes of schizophrenia. A large number of genetic and lifestyle factors, most of which remain unknown, likely determine the risk of developing this condition.
The Val108/158Met polymorphism has also been associated with other disorders that affect thought (cognition) and emotion. For example, researchers have studied this variation as a possible risk factor for bipolar disorder, panic disorder, anxiety, obsessive-compulsive disorder (OCD), eating disorders, and attention deficit hyperactivity disorder (ADHD). Studies suggest that these conditions may be related to inefficient processing of information in the prefrontal cortex. As with schizophrenia, however, many factors play a part in determining the risk of these complex disorders.
