5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression

  title={5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression},
  author={Lukas Pezawas and Andreas Meyer-Lindenberg and Emily M. Drabant and Beth A. Verchinski and Karen E. Mu{\~n}oz and Bhaskar S. Kolachana and Michael Egan and Venkata S. Mattay and Ahmad R. Hariri and Daniel R. Weinberger},
  journal={Nature Neuroscience},
Carriers of the short allele of a functional 5′ promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for… 

Variant in oxytocin receptor gene is associated with amygdala volume

Serotonin transporter genotype modulates functional connectivity between amygdala and PCC/PCu during mood recovery

It is suggested that 5-HTTLPR genetic variation modulates amygdala connectivity which subsequently affects its activity during mood regulation, providing an additional mechanism by which the S allele confers depression risk.

A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function

Evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus, and these neural characteristics predicted lower levels of reward dependence in male risk allele carriers.

Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis.

Serotonin transporter genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults

The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults

The data provide evidence for a functional network-based phenotype linking genetic variation in 5-HTTLPR to emotion regulation, and suggest that further critical evaluations of the association between 5- HTTLPR and amygdala activation are warranted.

Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety

Serotonergic genes modulate amygdala activity in major depression

The data suggest that the genetic susceptibility for major depression might be transported via dysfunctional neural activity in brain regions critical for emotion processing.

Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.

Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD, and emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.



A susceptibility gene for affective disorders and the response of the human amygdala.

A potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat is revealed, which may represent a classic susceptibility factor for affective disorders by biasing the functional reactivity of the human amygdala in the context of stressful life experiences and/or deficient cortical regulatory input.

Serotonin Transporter Genetic Variation and the Response of the Human Amygdala

Genetically driven variation in the response of brain regions underlying human emotional behavior is demonstrated and differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.

Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia

The data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.

Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter

Healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.

Meta-analysis of serotonin transporter polymorphisms and affective disorders

The results suggest that the S allele, or a neighboring allele in linkage disequilibrium, is recessive for MDD and possibly BPD, and with these small associations, confounding issues such as population stratification require addressing.

Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting

Meta‐analysis of the association between a serotonin transporter promoter polymorphism (5‐HTTLPR) and anxiety‐related personality traits

  • S. SenM. BurmeisterD. Ghosh
  • Psychology, Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2004
There is a strong association between the serotonin transporter promoter variant and neuroticism as measured in the NEO personality inventory and that non‐replications are largely due to small sample size and the use of different inventories.

A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety

The findings indicate that 5-HTTLPR may in fact have a small but reliable influence on personality, particularly in the manifestation of trait anxiety when measured with a neuroticism scale based on the five-factor model of personality.

Serotonin transporter: gene, genetic disorders, and pharmacogenetics.

Replicated studies have demonstrated that the SERT 5'-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the serotonin reuptake inhibitors (SRIs).