Genetics of Brain Function

Major Depression and Genetics

This is a summary of information about what is known about genetics and major depression. The links at the bottom of this page will direct you to more information about the symptoms and diagnosis of depression, and also to more detailed information about genetics of depression including articles in the scientific literature on which the following summary is based. There is also information about research on genetics of depression.

How common is major depression? At least 10% of people in the U.S. will experience major depressive disorder at some point in their lives. Two times as many women as men experience major depression.

How do we know that genes play a role in causing depression? Scientists look at patterns of illness in families to estimate their “heritability,” or roughly what percentage of their cause is due to genes.  To do this we find people with the disease who have a twin, and then find out whether the twin is also ill.  Identical (monozygotic) twins share 100% of their genes, while non-identical (“fraternal” or dizygotic) twins share 50% of their genes.  If genes are part of the cause, we expect a patient’s identical twin to have a much higher risk of disease than a patient’s non-identical twin.  That is the case for major depression.  Heritability is probably 40-50%, and might be higher for severe depression. 

This could mean that in most cases of depression, around 50% of the cause is genetic, and around 50% is unrelated to genes (psychological or physical factors).  Or it could mean that in some cases, the tendency to become depressed is almost completely genetic, and in other cases it is not really genetic at all.  We don’t know the answer yet.

We can also look at adoption studies, to see whether an adopted person’s risk of depression is greater if a biological parent had depression.  This also seems to be the case.

What about non-genetic factors?  There are probably many non-genetic factors that increase risk of depression, many of which are probably not yet known.  Severe childhood physical or sexual abuse, childhood emotional and physical neglect, and severe life stress are probably all risk factors.  Losing a parent early in life probably also increases risk to some extent.

If someone has a family history of depression, are they at very high risk?  If someone has a parent or sibling with major depression, that person probably has a 2 or 3 times greater risk of developing depression compared with the average person (or around 20-30% instead of 10%).

The situation is a little different if the parent or sibling has had depression more than once (“recurrent depression”), and if the depression started relatively early in life (childhood, teens or twenties).  This form of depression is less common – the exact percentage of the population is not known, but is probably around 3-5%. But the siblings and children of people with this form of depression probably develop it at a rate that is 4 or 5 times greater than the average person.

Is there a “depression gene”? Some diseases are caused by a single defective gene. Cystic fibrosis, several kinds of muscular dystrophy, and Huntington’s disease are examples.  These are usually rare diseases.  But many common disorders like depression, diabetes and high blood pressure are also influenced by genes.  In these disorders, there seem to be combinations of genetic changes that predispose some people to become ill.  We don’t yet know how many genes are involved in depression, but it is very doubtful that any one gene causes depression in any large number of people. 

So no one simply “inherits” depression from their mother or father.  Each person inherits a unique combination of genes from their mother and father, and certain combinations can predispose to a particular illness.

How are major depression and bipolar disorder related?  Most people who suffer from depression do not have episodes of mania.  We use the term major depression for depression without mania.  Most people who experience mania also have major depression.  We use the term bipolar disorder (or manic-depression) for this pattern.  Major depressive disorder and bipolar disorder are the two “major mood disorders.”  For more information on the symptoms of mania abd bipolar disorder, see the links at the bottom of this page.  Most people with major depression do not have close relatives with bipolar disorder, but the relatives of people with bipolar disorder are at increased risk of both major depression and bipolar disorder.

What about major depression and anxiety disorders?  There are probably genetic changes that can increase the predisposition to both major depression and to certain anxiety disorders including generalized anxiety disorder, panic disorder and social phobia.  Also, some people have a more general lifelong tendency to experience unpleasant emotions and anxiety in response to stress.  Psychologists use terms like “neuroticism” and “negative affectivity” to refer to this tendency, and people who have it are also more likely to experience major depression. 

However, many people who develop major depression did not have this type of personality before their depression started.

This page was written by:
Douglas F. Levinson, M.D.
Walter E. Nichols, M.D., Professor in the School of Medicine
Department of Psychiatry and Behavioral Sciences

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