Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression

Risch, Neil; Herrell, Richard; Lehner, Thomas; Liang, Kung Yee; Eaves, Lindon J.; Hoh, Josephine; Griem, Andrea; Kovács, Mária; Ott, Jürg; Merikangas, Kathleen R.

doi:10.1001/jama.2009.878

Cited by 1,541 publications

(1,261 citation statements)

References 69 publications

(114 reference statements)

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“…These findings support other studies and meta-analyses which suggest a relationship between the 5-HTTLPR S allele and MDD risk (Bogdan, Agrawal, Gaffrey, Tillman, & Luby, 2014;Kim et al, 2007;Kiyohara & Yoshimasu, 2010), although other meta-analyses have failed to replicate this finding (e.g. Risch et al, 2009). Moreover, firstdegree relatives of MDD patients have been observed to exhibit greater amygdala activity in response to negative emotional material relative to participants at low-risk for MDD (Monk et al, 2008;van der Veen, Evers, Deutz, & Schmitt, 2007).…”

Section: The Role Of Amygdala Function In Depressionsupporting

confidence: 89%

“…As previously discussed, there is a probable link between the 5-HTTLPR S allele and MDD vulnerability (Munafò, Durrant, Lewis, & Flint, 2009;Talati et al, 2015; however see: Risch et al, 2009), which may be related to altered patterns of functional amygdala activity (Costafreda et al, 2013). There is also abundant evidence to suggest that amygdala hyperactivity towards negative stimuli is related to long-term negative memory bias in depression (Hamilton & Gotlib, 2008).…”

Section: The 'Affect Tagging and Consolidation' (Atac) Modelmentioning

confidence: 98%

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The ‘affect tagging and consolidation’ (ATaC) model of depression vulnerability

Harrington

Pennington

Durrant

2017

Neurobiology of Learning and Memory

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Please cite this article as: Harrington, M.O., Pennington, K., Durrant, S.J., The 'Affect Tagging and Consolidation' (ATaC) Model of Depression Vulnerability, Neurobiology of Learning and Memory (2017), doi: http://dx.doi.org/10. 1016/j.nlm.2017.02.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. patients, suggesting that they may be vulnerability markers of major depressive disorder (MDD), rather than mere epiphenomena of the disorder. Neuroimaging studies have revealed that depression is also associated with heightened amygdala reactivity to negative emotional stimuli, which may also be a vulnerability marker for MDD. Several models have been developed to explain the respective roles of REM sleep alterations and negatively-biased amygdala activity in the pathology of MDD, however the possible interaction between these two potential risk-factors remains uncharted. This paper reviews the roles of the amygdala and REM sleep in the encoding and consolidation of negative emotional memories, respectively. We present our 'affect tagging and consolidation' (ATaC) model, which argues that increased REM sleep density and negatively-biased amygdala activity are two separate, genetically influenced risk-factors for depression which interact to promote the development of negative memory bias -a well-known cognitive vulnerability marker for depression.Predictions of the ATaC model may motivate research aimed at improving our understanding of sleep dependent memory consolidation in depression aetiology.

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Section: The Role Of Amygdala Function In Depressionsupporting

confidence: 89%

Section: The 'Affect Tagging and Consolidation' (Atac) Modelmentioning

confidence: 98%

The ‘affect tagging and consolidation’ (ATaC) model of depression vulnerability

Harrington

Pennington

Durrant

2017

Neurobiology of Learning and Memory

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“…Finally, a recent meta-analysis has questioned the existence of an interaction between SLEs and the 5-HTTLPR in the absence of a main effect, 36 although the validity of the study has been questioned. 37,38 Researchers remain divided on whether the genetic should be detected before testing for interactions.…”

Section: Limitationsmentioning

confidence: 99%

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

et al. 2010

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“…Clearly, this is controversial. On the one hand, there have been two negative meta-analyses that included a small number of reports to use homogeneous designs (k = 5 and 14, respectively; Munafò et al 2009;Risch et al 2009), many G × E investigations are under-powered (Duncan & Keller, 2011), and we observed some questionable research practices as we read. On the other hand, inclusive meta-analyses from Karg et al (2011) (k = 54) and Sharpley et al (2014) (k = 81) both reach positive conclusions, with Sharpley et al (2014) showing that the meta-analytic effect emerges across four separate design subtypes.…”

Section: Biased Conclusionmentioning

confidence: 86%