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Popular Press v. Scientific Literature:

Is SERT Responsible for Obsessive-Compulsive Disorder?

Obsessive-Compulsive Disorder & the SERT Gene

Obsessive-Compulsive Disorder (OCD) is a brain disorder which causes problems in information processing (OCF, 1998).  OCD occurs in 2.5–3% of the US population (OCD Centre, 2002).  People with OCD are often overwhelmed by recurrent thoughts (obsessions) which create anxiety, followed by repetitive behaviors or rituals (compulsions), aimed at reducing the distress caused by their obsessions (OCD Centre, 2002).

The human SERT gene, located on chromosome 17, codes for a serotonin transporter protein, used in the brain.  This gene is organized into 14 exons, which produce a transmembrane protein with 12 membrane-spanning domains (Figure 1).  The research described below focuses on the result of a mutation in this protein.

Figure 1 Human serotonin transporter protein. This figure depicts one artist's rendering of the SERT protein. The enlarged portion of the figure shows transmembrane region 8. The I425V substitution takes place within this region (as illustrated by the arrow). Image from full text article in Molecular Psychiatry. Permission granted by DL Murphy, M.D.

Popular Press

Gene Found for Obsessive Compulsive Disorder. To view article click here.

On November 4, 2003, MSNBC News declared: “Gene Found for Obsessive Compulsive Disorder.”  The title of this article, although accurate, is somewhat misleading.  The original research study, from which this review is derived, does report a mutation linked to OCD, but this mutation is rare among OCD sufferers.  The title of MSNBC's article leads the reader to believe that the gene causing all forms of OCD has been discovered.  It is not until much later in the article that the rarity of this OCD-causing mutation is even mentioned.

While the title is somewhat sensational, the rest of the article does an accurate job of presenting the findings of the study, without getting bogged down in the scientific background.

The scientific information is handled very concisely.  The article merely mentions that this OCD-causing mutation was found on the human serotonin transporter gene (SERT), a gene which “helps control how the body uses serotonin . . . a neurotransmitter linked with mood.”

However, the research method and results are covered in slightly more detail, outlining the composition of the 170-person study group and explaining that only two participants (both suffering from OCD) and their families carried this specific SERT mutation.  The article does note that among the seven people with this specific mutation (two participants and five family members), six suffered from OCD, and some from additional mental illnesses (Figure 2).

The “double dose” mentioned in the last paragraph refers to a second mutation found in both patients with the SERT mutation.  The article states that this mutation makes OCD conditions worse, and especially difficult to treat, but stops short of explaining the mechanism.

Scientific Journal

Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. To view article click here.

This original research article provides a much more detailed view of the findings and methodology associated with the study, while making no tabloid claims or predictions.  In contrast to the popular press article, the title of this paper – “Serotonin transporter missense mutation associated with complex neuropsychiatric phenotype” – succinctly summarizes the findings of the research, leaving no question about the results of the study and allowing no wild extrapolations from the reader.

This paper highlights the nature of the mutation in the SERT gene which was found in two families participating in the study.  All affected individuals in these families presented an adenine to guanine transversion at nucleotide 1273, resulting in a mutated SERT protein in which a valine (an amino acid) is substituted for the normal isoleucine.  This I425V substitution is located in transmembrane region 8 of the SERT protein and alters the secondary structure of this hydrophobic domain, resulting in proteins which are “locked” into the activated state.  Individuals suffering from this gain-of-function mutation experience defective regulation of SERT.  This effect may contribute to an inherited form of OCD, as well as a host of other neuropsychiatric disorders, including Asperger’s syndrome, autism, and anorexia.  However, the article notes that this I425V mutation is rare, and not responsible for these disorders in most individuals.

Of the 170 patients studied, only two presented this genetic mutation.  However, when the relatives of these patients were genotyped, seven of the fourteen members of the resulting pedigrees were heterozygous for the I425V mutation.  Of these seven people, six suffered from OCD or an OC personality disorder.

This paper goes on to address a topic that was only mentioned in the popular press piece – the “double-hit” effect.  The premise behind this hypothesis is that the probands and their siblings (who all had severe OCD with multiple and “somewhat unusual coexistant neuropsychiatric disorders”) also had a homozygous mutation on the promoter region of their SERT gene.  This variant increases serotonin uptake by producing more mRNA, which makes more SERT sites available, which causes two to three times the normal amount of transcriptional activity, as well as greater response to cyclic AMP and protein kinase C.  The combination of these two mutations within the SERT gene amplifies the gain-of-function effect of the I425V, producing the “double-hit” effect.

Figure 2 Families with OCD and the I425V substitution. This figure shows that seven of the fourteen family members of the I425V probands are heterozygous for the I425V mutation. Of these, six individuals suffer from OCD or an OC personality disorder. The seventh individual was diagnostically indeterminant (declining assessment interviews). Image from full text article in Molecular Psychiatry . Permission granted by DL Murphy, M.D.


The popular press article does a good job of communicating the results of the scientific literature in a way that the average reader will understand.  While it certainly lacks in scientific substance – barely mentioning the gene affected and ignoring the role of the SERT protein this gene encodes – covering these topics in an article of this nature would be too ambitious.  What’s more important, however, is that the information contained in this article is accurate.  Aside from a title, which may lead the reader to assume that the gene for OCD has been discovered, this is a well-written, easy-to-understand review of a fairly complex scientific phenomenon.

The article from the scientific journal is substantially more complex, dealing with the intricacies of the genetic mutation and consequent gain-of-protein-function, as well as particulars of experimental design and the “double hit” hypothesis.  While these details are not necessary for the average reader, they are certainly essential for anyone hoping to understand the mechanism behind this OCD phenotype.

In comparing these two sources, it has become obvious that the popular press and scientific literature have entirely different goals.  While the popular press aims to inform readers of scientific breakthroughs, these articles are oversimplified and often dramatized.  In this case, the popular press gives an accurate, although simplistic, portrayal of the original scientific data, but this is not always the case.  Caveat emptor!  To see the real data and gain a better understanding of what the research actually involved, it is always best to view the scientific literature.


Kua E, M Reder, MJ Grossel. 2004. Science in the news: a study of reporting genomics. Public Understanding of Science (13): 309-322.

[OCF]  The Obsessive-Compulsive Foundation.  1998.  What is OCD?  <>.  Accessed 2004 Sep 5.

OCD Centre, The.  2002.  OCD: Get Informed.  <>.  Accessed 2004 Sep 5.

Ozaki N, D Goldman, WH Kaye, et al.  2003.  Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype.  Molecular Psychiatry (8): 933-936.

Reuters.  2003 Nov 4.  Gene found for obsessive compulsive disorder.  MSNBC News: Health.  <>.  Accessed 2004 Sep 1.


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