Most brain disorders arise due to a mix of genetic, environmental, and lifestyle factors. Inheriting the genetic predisposition to develop a brain disease does not always mean that any person will have the symptoms of the disease, and the symptoms for some brain diseases may vary even in the same family. While we do not yet know the genetic causes of all brain diseases, we do know that in some families, there are many individuals who develop a specific disorder, for example, Alzheimer disease (AD), which tends to follow a similar medical course. For other disorders, it may be more unusual to find more than one person with the disease in any given family or the disorder may manifest itself differently in related family members.
What geneticists have done is to seek out the families with several affected members, and to enlist these families to help unravel the inborn causes of the disease. Most studies involve gathering medical history and personal lifestyle data from all of the participating family members in addition to obtaining a blood or saliva sample for DNA extraction. Many studies these days include whole exome or whole genome sequencing, where hundreds of differences in the genetic code can be detected. Other studies may look at another single gene or panel of genes that seem promising to the investigator. Another tool that may be used is to detect how the genes are expressed in the body. Scientists also are looking into environmental factors and how they play into the regulation of the genes. All of these methods yield results that then have to be analyzed together to reveal the causes, and hopefully the paths to treatment, for brain disorders.
For Alzheimer disease, we know that around 5% of people who have the disease develop symptoms at a very young age, before the person is 60 years old. These early-onset AD patients sometimes do not have a family history of AD, but often they do know that the disorder has been passed from parent to child. Several genes have been found to harbor mutations in families with early-onset AD. For the more typical late-onset disease, there is an association with a specific form of a gene APOE. Not everyone with the rare ε4 version of the gene will develop AD, but the chances of development is increased.
Attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) are diagnosed in increasing numbers of young children. While intelligence is normal, learning may be affected. Genetics plays a part in the development of ADD/ADHD, but environmental factors seem to contribute to the development of this disorder. Researchers are investigating the genes that bring an increased risk of ADD/ADHD as well as the other factors involved, including brain injury and nutrition as well as the changing social environment.
Epilepsy is a group of brain disorders in which the individual has recurring seizures. There are a variety of types of seizures that may occur, but usually the patient has a specific type or a set of seizure types. All seizures are due to abnormal electronic activity in the brain. There are many genes related to epilepsy, some of which cause childhood epilepsy and others associated with adult-onset. Some types of epilepsy are called autosomal dominant diseases because they are inherited directly from one parent. Other types require both parents to carry a mutation in the same gene, which is called autosomal recessive inheritance. There are also epilepsy genes located on the X chromosome. Epilepsy may also occur after damage to the brain from an injury, infection, tumor, or stroke. In itself, epilepsy is not contagious.
Mood disorders encompass a variety of debilitating conditions that range from dysthymia (with long term depressive symptoms not severe enough to disable an individual) to major depressive disorder (with symptoms severe enough to impact a person's ability to function normally). The duration of symptoms may be short, or seasonal, or occur post-partum. The affected individual may have symptoms that cause a break from reality, and therefore are called psychotic, or may include cycles of extreme lows and highs, commonly called manic-depressive or bipolar affective disorder. All of these mood disorders may be based on a genetic predisposition as well as other environmental and emotional factors. Bipolar disorder is one type of mood disorder that tends to run in families. If a parent or sibling has bipolar disorder, a child has a four to six times higher chance of developing the disorder, compared to individuals without any family history of bipolar disorder. However, in studies of identical twin pairs in which one twin was diagnosed with a bipolar disorder, the other twin was not diagnosed with a bipolar disorder in many families. These results demonstrate that the genetic contribution is not the only piece to the puzzle of what causes a mood disorder.
Multiple sclerosis (MS) is another more common debilitating brain disease. A person with multiple sclerosis is more likely to be female than male, and the onset of symptoms, for example, weakness and numbness, is more likely to occur between ages 20 and 40 years. While some familial cases have been found, the majority of affected individuals are the sole person in a family with MS. In this disease, the body’s own immune system causes damage to the protective cover surrounding the nerves. A person is more likely to contract MS if a relative has MS or if the person lives in a region where MS is more common. There may well be an environmental factor, for example, a virus or toxin, that causes MS in susceptible people.
Another common brain disorder is Parkinson disease (PD). PD is commonly a late-onset disease, but may occur in people below the age of 50 years. The main issue in PD is a shortage of dopamine, a chemical messenger in the brain. Other chemical messengers, like norepinephrine, are also diminished. The onset may be subtle, with difficulty initiating movement, slowed handwriting, or a mask-like facial expression. Often the person with PD develops a tremor. There have been at least 5 genes associated with familial cases of PD, but most patients are the only individual in his or her family with the disease. Considered a multifactorial disease, PD has been connected with environmental toxins and viruses, mitochondrial dysfunction, and even head trauma.
While an individual has to experience a severe trauma to be diagnosed with post-traumatic stress disorder (PTSD), not everyone who experiences the same stressful situation comes down with PTSD. We know that how we form memories of fear factors into whether or not someone has PTSD after a horrible trauma. Scientists are investingating the genes associated with fear memories, and variations in those genes likely are one of the underlying reasons some people have PTSD.
Schizophrenia is a serious chronic psychiatric disease. This disorder is another inwhich both genetics and environment plays a part. We know that about 1% of the general population develops schizophrenia, although around 10% of those with a close relative with the disease will also develop schizophrenia. The risk is highest for the identical twin of a schizophrenic person, reaching 40 to 65%, but not as high as 100%, the risk of an identical twin contracting a disorder that is caused strictly by genetics. Research is looking into different important chemicals in the brain and how they may misfunction. It is a complex disease, implying that it will take intense research to unravel its causes.
Traumatic brain injury (TBI) has become an important topic in brain health due to two different groups affected by TBI: soldiers and other victims of war and football and other sports players who have repeated concussions. While a person needs to suffer an head injury in order to be diagnosed with TBI, both differences in individuals' reactions to the severity of an injury and potential therapies for the injury may be uncovered through genetic investigations.