Causes of Bipolar Disorder

If you or a loved one lives with bipolar disorder, you may wonder what caused the illness to begin. This question is both interesting and important, as the answers can help with managing symptoms and planning a family.

Doctors generally accept that bipolar disorder is caused by a mix of interacting genetic defects and stressors from one’s environment–while genes can predispose someone for the illness, stress can trigger the onset of symptoms. The brain is subject to many biological processes, governed by numerous different genes and outside influences. As a result, a complex brain illness such as bipolar disorder probably has many contributing factors. Scientific findings confirm this complexity, and some discoveries are already leading to helpful therapies.

It seems that genetic defects are bipolar disorder’s primary contributing factor. It was first noticed over a century ago that risk to bipolar disorder risk runs in families.1 Studies now show a 10 times greater risk of developing bipolar if a first degree relative, such as a parent, has the disorder, for an overall 8.7% chance. How can we know if this increase is due to genetic heritability (“nature”) or upbringing (“nurture”)? Studies of twins who grow up together, which compare the frequency with which pairs of identical twins share the disease vs. the frequency for pairs of fraternal twins, have helped to show what part of this illness comes from genes and what part from upbringing. The key thing that makes these studies work is that identical twins share 100% of their genes, while fraternal twins share only half their genes. So, a greater sharing of bipolar disorder among identical twins would indicate that genes are a greater influence than family environment. In fact, such studies have found a much greater chance (around 65%) that identical twins will share the disorder, vs. around a 5 to 20% chance for fraternal twins. Thus, these results favor nature over nurture. This conclusion plays out in studies of families adopting children. First-degree adoptive relatives of people with bipolar showed about the same risk of developing the disease as did the general population, further showing early family environment as a minimal factor. In general, studies have placed the genetic heritability of bipolar disorder at 60-85%, and have produced no consistent evidence for influence from early family environment.2

Exactly which mixes of genes can lead to bipolar disorder still remains to be found. About ten major genes have so far been implicated through association studies. In these studies, genetic scans of groups of people both with and without bipolar reveal areas of DNA distinctive to people with the disease.3 Probably, each of these genes plays a small role in the buildup of bipolar susceptibility.4 Much research is on the horizon: How do these genes influence the makeup of the brain to produce bipolar symptoms? If the answers can be found, specific new targets for medications will follow.

Did you know that some bipolar risk genes can also cause risk for schizophrenia and vice versa? Several studies have shown that the two diseases are closely genetically related. In fact, a 2009 study of Swedish families has shown that the genetic risk factors for bipolar disorder and schizophrenia overlap by 63%.5 One factor that may separate the diseases is whether or not certain large sequences of duplicate genetic code are present in someone’s genome. A U.K. study suggests that if someone is genetically predisposed for at least one of these diseases and is missing these chunks of DNA, he or she is more likely to develop schizophrenia. If they are present, bipolar disorder is more likely, the study suggests.6

Much attention has been given to the frequent mixing of substance abuse with bipolar disorder as a potential influence in the onset of symptoms. One review of research data shows that bipolar patients who abuse drugs develop symptoms earlier and experience a rockier course of illness than those who do not.7 But whether this correlation implies a cause one way or another is not yet known–perhaps drugs worsen symptoms, or perhaps worse symptoms induce a stronger desire to self-medicate.

As you might expect, many studies do indicate that life experiences influence bipolar symptoms. Evidence abounds that stressful life events may in fact bring on manic, hypomanic, or depressive episodes by disturbing the sufferer’s sleep-wake cycles, and, in turn, his or her brain chemistry. For example, striving to do well on final exams (a time when many students sleep little) was shown to produce manic or hypomanic episodes in many bipolar students. Other studies have shown that one’s current family relationships are strongly influential: living with more emotionally expressive or more critical family members can cause more frequent relapses and longer recovery times. Also, there is considerable evidence that a certain attitude set (i.e, a strong goal orientation, prizing of autonomy, perfectionism, and self-criticality) compounds the risk of symptom onset under stress. Fortunately, cognitive behavioral therapy has been shown to help improve such attitudes and reduce bipolar symptoms. And, the nurturing and maintenance of supportive family and social relationships can help a lot, as studies clearly show.8

So, if your family history seems to point to a risk for bipolar disorder for you or your children, please keep that in mind as you plan for the future. Fostering strong relationships and positive attitudes can make a difference in improving both your and your children’s health.

For more information and help for bipolar and other mood disorders, please see the Depression and Bipolar Support Alliance website.

Sources:

1) Barondes, Samuel H., Mood Genes: Hunting for Origins of Mania and Depression. Oxford University Press, 1998.

2) Smoller, Jordan W. and Finn, Christine T., Family, Twin, and Adoption Studies of Bipolar DisorderAmerican Journal of Medical Genetics Part C (Semin. Med. Genet.) 123C:48–58 (2003). Article PDF.

3) Barnett, JH and Smoller, JW., The Genetics of Bipolar DisorderNeuroscience, November 24, 2009. Abstract on PubMed.

4) Sklar, P et al, Whole-genome Association Study of Bipolar DisorderMolecular Psychiatry 2008 (13). Article PDF.

5) Lichtenstein P, Yip BH, Björk C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based studyLancet. 2009 Jan 17 ; 373(9659):234-9. Abstract on PubMed.

6) Wilcox, Victoria L. Studies Question Role for CNVs in Bipolar DisorderSchizophrenia Research Forum, April 15, 2010. Article online.

7) Brady, Kathleen T.; Sonne, Susan C. The relationship between substance abuse and bipolar disorderJournal of Clinical Psychiatry. Vol 56(Suppl 3),1995, 19-24. Abstract on PsycNET.

8) Alloy, Lauren B.; Abramson, Lyn Y.; Urosevic, Snezana; Walshaw, Patricia D.; Nusslock, Robin; Neeren, Amy M.; The psychosocial context of bipolar disorder: Environmental, cognitive, and developmental risk factorsClinical Psychology Review, Volume 25, Issue 8, The Psychology of Bipolar Disorder, December 2005, Pages 1043-1075, ISSN 0272-7358, DOI: 10.1016/j.cpr.2005.06.006. Abstract on ScienceDirect.

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