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Have any family members been known to be particularly energetic or eccentric? In the past, people politely described relatives with various degrees of mental illness as eccentric.

      ✔ Has anyone in the family suffered from physical symptoms such as chronic exhaustion, pain, or digestive problems? These symptoms may be physical manifestations of mood and anxiety disorders.

      

Families can be particularly secretive, especially when protecting the reputation of the dead. People can become even more defensive if you confront them while you’re in the throes of mania. Choose a time when you’re levelheaded to explain how important an accurate and detailed family history is for your diagnosis.

Realizing that genetic susceptibility is only one risk factor

      Having a genetic susceptibility to bipolar disorder doesn’t guarantee that you’ll experience symptoms. The most recent research, described in the next two sections, suggests that a variety of genetic changes can create a susceptibility to developing the disorder. But susceptibility isn’t destiny – bipolar disorder seems to occur due to a combination of genetic and nongenetic factors. Although you can’t control all the possible triggers, managing the ones you can control may reduce your risk of developing the disorder, and doing so certainly may help lessen the severity of your illness and improve your prognosis if it occurs.

      

Highly charged life events, both positive and negative, seem to relate to the development of symptoms, but other biological events – including the number of episodes that you experience – are likely to be involved, as the next section explains. The severity of your underlying susceptibility is also important. Some subtypes of bipolar found in some families that are more extreme and more likely to evolve into illness without major or well-defined triggers, whereas other forms may require higher doses of stress responses to fully develop.

Grasping the genetic complexities

      Even though indisputable evidence proves that bipolar disorder has strong genetic components, science has more recently been able to show clearly that that there is no single bipolar gene. What’s called bipolar disorder, based on emotional and behavioral symptoms, actually seems to be a group of disorders that have different underlying biological stories. Because genetics play a big role in these stories, scientists are likely to find many different types of genetic changes that contribute to the various causes of bipolar disorder. Current research has started to put some pieces of these stories together and suggests the following main points:

      ✔ Bipolar disorder seems to be the result of small changes in a high number of genes rather than big changes in just a few genes; high-volume studies that look at thousands of genomes are needed to pin down the specific genes involved in bipolar. (A genome is an organism’s complete set of DNA, its genetic makeup.) The small changes that have been found aren’t usually unique to bipolar disorder, but have a higher rate of occurrence in people with bipolar disorder compared to those without bipolar.

      ✔ Studies show a number of genetic changes that overlap between bipolar disorder and other conditions, especially schizophrenia and unipolar depression. Recently, a large and much publicized study published by the Cross-Disorder Group of the Psychiatric Genomics Consortium entitled “Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs, published in the journal Nature Genetics, uncovered a shared genetic risk with autism spectrum and ADHD, in addition to depression and schizophrenia. However, researchers have also identified a number of genetic changes that seem to be specific to bipolar disorder.

      ✔ The numerous genetic factors uncovered so far affect a wide variety of structures and functions throughout the body. Many other studies are looking at how the brains and bodies of people with bipolar disorder differ from those without (see the later section, “Examining the Circuitry of Bipolar”). The integration of the genetic studies and this other research is where the big picture of bipolar disorder is unfolding.

      ✔ Because bipolar isn’t 100 percent genetic, another important goal is to understand how nongenetic factors interact with the genetic risk factors to cause someone to actually develop bipolar disorder, as we explain in the next two sections.

Flipping the bipolar switch: Epigenetics

      Epigenetics is the study of changes that affect how genes are expressed without affecting the genes themselves. These changes occur through a variety of chemical interactions with the DNA. Sometimes these changes in expression occur as part of typical development and function, but some changes can disrupt normal processes and healthy cell function.

      The science of epigenetics helps to explain the interplay between nature and nurture – how an organism’s genotype (genetic makeup) interacts with the environment to produce the organism’s phenotype (observable characteristics). External events such as parental neglect or other trauma or stress may trigger chemical changes to DNA, which affect how a person’s genes are expressed. And these changes can pass to the next generation. So, for example, if an expectant mom has been exposed to chronic stress that has affected her mood-related genes, then the stress effect on the gene (not just the gene itself) can be passed on to her child. As a result, the child’s own genes as well as the effects of long-term stress on her mother’s genes affect the child’s likelihood of eventually exhibiting depression or other mood disorders.

      Investigating Nongenetic Factors

      Genetic studies indicate that about 60 to 70 percent of bipolar disorder is related to inherited factors, but a variety of nongenetic factors affect how these genes are expressed. Many of these stressors are present in the very early phase of brain development – before birth and in the first months and years of life. However, scientists also believe that ongoing nongenetic factors contribute to the development of bipolar disorder and its course over time. Some of these factors include the following:

      ✔ Stressful life events: Studies of people with bipolar disorder have found a number of abnormalities in the biological systems that regulate the body’s response to various types of stress. Interactions between these vulnerable systems and environmental stress more than likely play an important role in both the development and progression of bipolar disorder. Acute life events have been found to occur more frequently before mood episodes in people with bipolar disorder.

      ✔ Early life stress: That same interaction between impaired stress response systems and stress may occur many years before the development of bipolar disorder. Studies suggest that early childhood trauma is associated with a higher risk of bipolar disorder in adulthood.

      ✔ Substances: Alcohol and/or drug abuse often accompanies bipolar disorder. Some of this may be self-medication – using substances to dull pain and discomfort in the short run. However, substance abuse and bipolar disorder may have overlapping genetic risk factors, so that rather than being a behavioral response to the illness, these conditions may develop alongside one another. Some evidence even suggests that the use of alcohol and drugs may increase the risk of developing bipolar disorder, which raises the question of whether early intervention with drug and alcohol use can help reduce the likelihood of ever having that first mood episode. Tobacco use is also being looked at as possibly interacting negatively with genetic vulnerabilities to bipolar disorder.

      ✔ Nutrition: Although no research points to specific nutritional triggers for bipolar disorder, people with bipolar disorder have higher rates of illnesses such as cardiovascular disease and type 2 diabetes. These conditions create their own stress and physical damage. Healthful nutrition is an important part of limiting the development and progression of these conditions, which can reduce their negative effects.

      ✔ Infection: Studies have suggested that maternal infections, particularly with the flu virus, during pregnancy are associated with higher rates of bipolar disorder I in adulthood. The overlap of the infection with genetic risk factors may be a contributing factor to some people’s bipolar disorder. Some research shows a higher rate of infection with toxoplasmosis (a parasite found in cat feces) in people with bipolar disorder, and the current thinking is that the infection interacts

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