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5-HTT genotype effect on prefrontal–amygdala coupling differs between major depression and controls

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Abstract

Rationale

In major depression, prefrontal regulation of limbic brain areas may be a key mechanism that is impaired during the processing of affective information. This prefrontal–limbic interaction has been shown to be modulated by serotonin (5-HTT) genotype, indicating a higher risk for major depressive disorder (MDD) with increasing number of 5-HTT low-expression alleles.

Objective

Functional magnetic resonance imaging was used to assess neural response to uncued unpleasant affective pictures in 21 unmedicated patients with MDD compared to 21 matched healthy controls, taking into account genetic influences of the 5-HTT (SCL6A4) high- and low-expression genotype.

Results

Healthy controls displayed greater prefrontal activation (BA10) to uncued negative pictures compared to patients with MDD. While in healthy controls prefrontal (BA10) activation and BA10–amygdala coupling increased with the number of 5-HTT low-expression risk alleles, this effect was abolished, and even reversed, in patients with MDD. In MDD, connectivity decreased with severity of depressive symptoms (HAMD total score).

Conclusion

These findings suggest that increased medial prefrontal (BA10) activation and BA10–amygdala connectivity may counteract the risk for MDD in healthy carriers of 5-HTT low-expression alleles, while this protective factor might be lost in patients who actually suffer from MDD. Prefrontal–limbic regulation in risk populations could be a target of early interventions and should be the focus of further research.

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Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) DFG He 2597/4-3 and 7-3 and STE 1430/2-1.

Competing interest statement

The authors declare that they have no competing financial interests.

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Authors and Affiliations

  1. Department of Psychiatry, Charité University Medicine Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Eva Friedel, Florian Schlagenhauf, Philipp Sterzer, Soyoung Q. Park, Felix Bermpohl, Andreas Ströhle, Meline Stoy, Imke Puls, Claudia Hägele, Jana Wrase & Andreas Heinz

  2. NeuroImage Nord, Department of Neurology, University Clinic Hamburg-Eppendorf, Hamburg, Germany

    Christian Büchel

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  1. Eva Friedel
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  2. Florian Schlagenhauf
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  3. Philipp Sterzer
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  4. Soyoung Q. Park
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  5. Felix Bermpohl
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Corresponding author

Correspondence to Eva Friedel.

Additional information

Eva Friedel, Florian Schlagenhauf, and Philipp Sterzer contributed equally to this work.

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Friedel, E., Schlagenhauf, F., Sterzer, P. et al. 5-HTT genotype effect on prefrontal–amygdala coupling differs between major depression and controls. Psychopharmacology 205, 261–271 (2009). https://doi.org/10.1007/s00213-009-1536-1

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