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Forschungsarbeit

Allelic variation in the serotonin transporter promoter modulates cortical excitability

by Roger Marek (17.08.2009)

During my internship at the Experimental and Clinical Neurosciences (ECN) Elite Master's programme at the University of Regensburg, I investigated indicators for a genetic variation linked to depression. For this study, we used a method called 'transcranial magnetic stimulation' (TMS). TMS is a non-invasive neuronal technique that can be applied relatively easy. The basic principle behind TMS is that magnetic waves induce electric currents in neurons. Depending on the stimulation frequency, TMS allows to inhibit or excite neuronal signalling. So far, TMS has mainly been used to treat tinnitus (a phantom noise which is perceived as a continuous sound in the ear) or depression. Especially depression is a disease which can be resistant to medication. TMS therapy has been shown to significantly reduce the symptoms in depressed patients as well as in persons suffering from tinnitus. A major advantage of using TMS is that it has little side effects. The only discomfort that patients experience is an excitation of cranial nerves. This is normally tolerated after a few therapy sessions. TMS mainly affects neuronal signalling in areas which are located on the surface of the brain (cortex) as the strength of magnetic stimulation is limited. Tinnitus is treated by stimulating the auditory cortex whereas depression is treated by targeting the prefrontal cortex.

Illustration of the magnetic field – induced by a current flowing through the coil – which is capable of exciting or inhibiting neurons located in a specific region of the cortex.[Bildunterschrift / Subline]: Illustration of the magnetic field – induced by a current flowing through the coil – which is capable of exciting or inhibiting neurons located in a specific region of the cortex.

I worked on a study that did not use TMS as a treatment method but as a method that tells us something about a genetic variation. One major neurotransmitter which plays a crucial role in depression is the neurotransmitter 'serotonin'. The amount of serotonin in the synapses of neurons of the prefrontal cortex has been shown to be reduced in depressed patients compared to healthy people. One cause for this reduction in serotonin could be an allelic variation in the gene which encodes the serotonin reuptake transporter (5-HTTLPR). This short alleles lead to a disrupted reuptake of the neurotransmitter back into the synapse and a subsequent reduction of the release of serotonin from the synaptic terminals of the neuron.
 So, how does TMS tell us something about this gene? Magnetic excitation of an area in the motor cortex leads to measurable muscle contraction in the fingers. By using a technique called paired-pulse TMS, we were able to measure a parameter of cortical excitability (called 'short intracortical inhibition': SICI). Our study showed that people who carried a variation of the 5-HTTLPR gene showed a significantly reduced SICI compared to people who carry the normal gene. This study serves as a first step towards testing patients or healthy persons for a possible genetic disposition for depression. The results of this study have been published in the journal Biological Psychiatry, 2009, 66, 283-286.


Roger Marek
* 1980

Stationen
  • 2000-2004
  • Study in Chemistry at the University of Applied Science, Wintherthur, Switzerland.
  • 2006-2007
  • Diploma for Graduates in Neuroscience, University of Otago, New Zealand.
  • 2007-2009
  • Master of Neuroscience, University of Regensburg, Germany.
  • Since 2009
  • PhD at the University of Queensland, Brisbane, Australia.

Veröffentlichungen
  • The study has been published in the journal Biological Psychiatry, 2009, 66, 283-286.