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Depression Gene

Why is Eeyore so blue?

The CREB1 Gene:

The CREB1 gene encodes several proteins variants(called CREB1 a,b, and c) through alternate splicing that have several functions in the nervous system. (see CREB1 Cell article for details)  Researchers have pinpointed this gene's located to chromosome 2 (specifically 2q-32.3-q34) (link).  cAMP-response-element-binding-protein 1 (CREB1) is involved in the transcriptional regulation of genes that are induced by cAMP.  It is believed that this gene plays an important part in neurons involved in memory in the hippocampus.  "Pharmacological and two-pathway experiments suggest a model in which VP16-CREB activates the transcription of CRE-driven genes and leads to a cell-wide distribution of proteins that prime the synapses for subsequent synapse-specific capture of L-LTP by a weak stimulus." (link)  Recent research by Zubenko et al of University of Pittsburgh School of Medicine has linked CREB1 to mood disorders in women.  The mechanism linking this gene/protein to mood disorders is unclear.   Zubenko performed linkage studies comparing 80 families with major depressive disorder (MDD) to individuals with milder mood disorders.  In comparing the genomes of these two groups Zubenko found 19 loci with variations believed to be connected to MDD.   The region of chromosome 2 containing CREB1 had the strongest connection to mood disorders in women.  Zubenko found that variations in the CREB1 promoter and intron 8 are associated with mood disorders in women but not men (link).  This finding lead researchers to hypothesize that CREB1's effect on mood is sex dependent.  Zubenkoís findings also support the belief that sex dependent markers exist for depression and mood disorders and that some cases of depression (specifically MDD) are indeed hereditary.

The CREB1 gene and Major Depressive Disorder in women

What does CREB1 do?

 Chromosomal location of CREB1 gene associated with depression

Gene Map for 2q-32.3-q34

Popular Press:

The popular press and scientific press articles both responded to the findings by Zubenko et al at the University of Pittsburg School of Medicine in the fall of 2002.  Both articles were quite clear in their reporting of Zubenkoís findings on the role CREB1 might play in major mood disorders in women.  The popular press article in the Pittsburgh Post Gazette notes that the CREB1 protein role in regulating other genes as well as its functions in memory.  It explains that over or under production of the CREB1 protein could alter brain chemistry and thus mood.  The article reiterates Zubenkoís warning that other genes in the region of CREB1 may also play a role in brain chemistry and mood disorder.  Thus, the article is not quick to claim the discovery of the one gene that causes depression.  Surprisingly, this article revealed information about CREB1ís interaction with estrogen receptors as a possible reason for its strong effect on women versus men.  This finding was not clearly stated in the abstracts of the scientific articles.

The 'Depression Gene" in the popular press

A second article in a popular scientific magazine New Scientist noted that Zubenko's study found 19 loci within the human genome that "contain genetic variations that raise the risk of a severe form of  depression."   The article notes that the statistical likelihood that the linkage of depression to CREB1 results from chance is less than one in a billion.  The article also explains the basic methodology behind Zubenko's research.  The article explains how Zubenko followed 81 families with high incidence of MDD, compiling genetic profiles on 520 people.  The article goes on to note that Zubenko then compared patients who are susceptible to MDD to those suffering from mild forms of mood disorder.  In this way, the article sheds more light on the nature of Zubenkoís research than was available from the Nature article's abstract.  (While the abstract to Zubenkoís Nature article "sequence variations in CREB1 cosegregate with depressive disorders in women" does not note the methodology of research, it is assumed that if given full access to the article such methodology would be revealed).  Overall, both press articles gave a fair and honest report of Zubenkoís research and finding without alienating non-scientific audiences.  Further, both articles did not overstate the findings in an attempt to oversimply the research.  Neither article made reductive claims that Zubenko had found the sole "depression gene".

The "Depression Gene" in the scientific popular press

Background Information: Previous Research involving CREB1


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