Anxiety & Depression 5-HTTLPR DNA Test

This test detects a genetic variation, known as the “grouchy” gene, which affects serotonin levels and increases the risk of anxiety and depression.

What is serotonin?
Serotonin is a neurotransmitter in the brain that gives us feelings of pleasure and well-being. When serotonin is released from cells in the brain or neurons it sends out signals to be happy and content. The role of the 5-HTT serotonin transporter is to move serotonin from the synaptic cleft to the presynaptic neuron, allowing serotonin recycling in a sodium-dependent manner. The 5-HTT serotonin transporter is also important to maintain functional neural circuits connecting the amygdala and the cingulate regions of the brain. The 5-HTT serotonin transporter is encoded by the SLC6A4 gene, and it is within the 5-HTTLPR region of this gene that the “grouchy” variation occurs.

The “grouchy” gene
Individuals with the “grouchy” gene have the short version of the 5-HTTLPR region of SLC6A4. These individuals produce lower levels of the serotonin transporter, and have smaller amygdala and cingulate regions – two brain regions involved in emotional responses. This results in an increased risk of:

  • Grumpy or sad feelings
  • Anxiety related behaviour and stress response
  • Antisocial behaviour
  • Impulsiveness
  • Attention deficit disorder
  • Psychological disorders such as autism, depression, bipolar disorder
  • Addictive behaviour
  • Sudden infant death syndrome
  • Response to antidepressants
How is the “grouchy” gene inherited?
The SLC6A4 gene is located on chromosome 17. We inherit two copies of the gene – one from each parent. Inheriting one or two copies of the short (“grouchy”) version is linked to an increased risk of depression.

Response to antidepressants
The “grouchy” variant of the SLC6A4 gene is associated with a decreased response to selective serotonin reuptake inhibitor (SSRI) antidepressants. SSRIs (e.g. Prozac, Zoloft and Paxil) are commonly used as first-line treatment of depression, but 30-40% of affected people do not appear to benefit as well from this treatment. The molecular target of SSRIs is the 5-HTT serotonin transporter protein. Individuals with the “grouchy” variant produce lower levels of this protein, hence a decreased target for the SSRI antidepressant. Alternative antidepressants may be recommended for patients carrying the “grouchy” gene.

DNA testing for the “grouchy” gene
A simple DNA test can be done to find out which form of SLC6A4 a person has inherited. The test determines the length of the 5-HTTLPR region and distinguishes between the short form and the long form.

People with two copies of the short, “grouchy” form are more likely to be unhappy and will pass this form of the 5-HTT gene to all of their children. People with two copies of the long form, have a decreased risk of unhappiness and depression. Heterozygotes have one copy of the long form and one copy of the short form. Having one copy of the “grouchy” gene also impacts the level of happiness and these individuals have a 50% chance of passing the “grouchy” gene to their children.


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