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Searching for the Genetic Basis of Depression

written by: Arlin Cuncic • edited by: Paul Arnold • updated: 5/20/2011

Genes are the blueprints that code many of the processes in our bodies, including the regulation of brain chemicals that play a role in the development of depression. Although no single depression gene has been found, several have been identified that may confer risk of clinical depression.

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    Is there a depression gene? Studies have shown that a person with a first-degree relative with depression has a 20-30% chance of also developing the disorder, compared to 10% for those in the general population. Although it is unlikely that there is a single depression gene, evidence exists that one or more genes may predispose some people to develop the disorder. For those who are genetically vulnerable, other risk factors such as childhood abuse, stressful life events, and a pessimistic personality pattern may combine to increase the likelihood that depression will develop.

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    Heritability of Depression

    One way that researchers determine the role that genes play in the development of depression is through heritability studies. Heritability refers roughly to the percentage of the cause of depression that is due to genetics. Heritability studies are also known as "twin studies", because they involve comparing the prevalence of a disorder among identical (monozygotic) and fraternal (dizygotic) twins. Identical twins share 100% of their genes, whereas fraternal twins only share 50% of their genes. If genetics play a role in depression, it would be expected that an identical twin would be more at risk of also suffering with the disorder than a fraternal twin; findings have confirmed this result (Kendler et al., 2006).

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    Serotonin Transporter Gene

    In 2003, the serotonin transporter gene 5-HTT was found to affect the likelihood of developing depression after experiencing stressful life events (Caspi et al., 2003). In a study of 800 young adults, those who had at least one "short" variant of 5-HTT (everyone has two copies of the gene that can be either "long" or "short") were more likely to become depressed after stressful life experiences than those with two "long" variants. Having two "short" variants of 5-HTT conferred the worst risk; those with this variant were also more likely to become depressed as life circumstances became more stressful. Having at least one "short" variant of 5-HTT may be a risk factor for depression.

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    Stress Release Hormone

    Bradley et al. (2008) studied the impact of the gene CRHR1 on depression among 621 adults. CRHR1 is a gene that impacts the stress-relief hormone CRH, also known as the corticotrophin-releasing hormone. Study results showed that among adults who had experienced abuse as a child, there were half as many depressive symptoms reported by those people with a protective version of CRHR1 than those without a protective version.

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    Atypical DNA Sequence

    Another gene implicated in the development of depression is the atypical DNA sequence named G1463A. People with this gene variation are more likely to have very low levels of serotonin and suffer from major depression than those who do not. In addition, response to treatment with medications such as Prozac and Zoloft (that act on serotonin) is poorer for this group of people.

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    Bipolar Genetic Hotspot

    A 2010 study led by Francis McMahon, M.D., of the National Institutes of Mental Health (NIMH) Mood and Anxiety Disorders Program investigated potential genetic causes of depression through a genome-wide meta-analysis of five studies involving 13,600 people (McMahon et al., 2010). Although the researchers did not find a common gene with a large risk for mood disorders, they did identify a potential genetic hotspot for bipolar and unipolar depression. People with either disorder were more likely to have risk versions of the gene PBRM1, which is the blueprint for a protein involved in regulating gene expression. People with one copy of the risk version of the gene were 15% more likely to suffer with a mood disorder.

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    Stronger Brain Responses

    Researchers at the University of Michigan identified a genetic variant linked to an increased risk for major depressive disorder (Mickey et al., 2011). People whose genetic code produces lower amounts of the chemical neuropeptide Y (NPY) had stronger psychological responses to pain and brain responses to negative stimuli. Neuropeptide Y (NPY) is involved in regulating appetite and stress.

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    It is evident that mood is affected by multiple genes. As more genes involved in the development of depression are identified and their functions understood, treatments can be tailored to each individual. For example, medications can be chosen that best align with the type of depression being experienced. Although there is still much to be learned, the genetic picture is becoming clearer.

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    References

    Bradley, RG. et al. "Influence of Child Abuse on Adult Depression: Moderation by the Corticotrophin-Releasing Hormone Receptor Gene" Archives of General Psychiatry. American Medical Association, 2008.

    Caspi, A. et al. "Influence of Life Stress on Depression: Moderation in the 5-HTT Gene" Science. American Association for the Advancement of Science, 2003.

    Harvard Medical School "What Causes Depression?", http://www.health.harvard.edu/newsweek/what-causes-depression.htm.

    Kendler, KS., Gatz, M., Gardner, CO. & Pedersen, NL. "A Swedish national twin study of lifetime major depression" American Journal of Psychiatry, 2006.

    McMahon, FJ. et al. "Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1" Nature Genetics. Nature Publishing, 2010.

    Mickey, BJ. et al. "Emotion Processing, Major Depression, and Functional Genetic Variation of Neuropeptide Y" Archives of General Psychiatry, 2011.

    Miller, AR. Living with depression. Infobase Publishing, 2008.

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