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Related Experiment Video

Updated: Jun 23, 2026

Exploring the Neural Correlates of Cognitive Reappraisal in Obsessive-Compulsive Disorder Using Task-based Functional Magnetic Resonance Imaging

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

Eva Friedel¹, Florian Schlagenhauf, Philipp Sterzer

¹Department of Psychiatry, Charité University Medicine Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany. eva.friedel@charite.de

Psychopharmacology

|April 24, 2009

Summary

Major depression involves impaired prefrontal-limbic regulation, influenced by serotonin transporter (5-HTT) genotype. Healthy individuals with risk alleles show protective brain responses, which are lost in patients with major depressive disorder (MDD).

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Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression

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Published on: May 19, 2015

Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Major depression (MDD) is linked to impaired prefrontal cortex regulation of limbic areas during affective processing.
Serotonin transporter (5-HTT) genotype modulates prefrontal-limbic interaction, with low-expression alleles increasing MDD risk.

Purpose of the Study:

To investigate neural responses to affective stimuli in unmedicated MDD patients versus controls.
To examine the influence of 5-HTT genotype (high- and low-expression) on these neural responses.

Main Methods:

Functional magnetic resonance imaging (fMRI) was used.
21 unmedicated MDD patients and 21 healthy controls were studied.
Participants viewed uncued unpleasant affective pictures.

Main Results:

Healthy controls showed greater medial prefrontal (BA10) activation to negative pictures than MDD patients.
In controls, BA10 activation and BA10-amygdala coupling increased with 5-HTT low-expression alleles.
This protective effect was absent or reversed in MDD patients, with decreased connectivity correlating with symptom severity.

Conclusions:

Increased medial prefrontal (BA10) activation and BA10-amygdala connectivity may protect against MDD in healthy individuals with 5-HTT low-expression alleles.
This protective mechanism appears compromised in individuals with MDD.
Prefrontal-limbic regulation in at-risk populations warrants further research for early intervention targets.