Beyond genotype: serotonin transporter epigenetic modification predicts human brain function

Nikolova, Yuliya S.; Koenen, Karestan C.; Galea, Sandro; Wang, Chiou Miin; Seney, Marianne L.; Sibille, Etienne; Williamson, Douglas E.; Hariri, Ahmad R.

doi:10.1038/nn.3778

Cited by 111 publications

(136 citation statements)

References 29 publications

(41 reference statements)

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“…The authors provided evidence for the utility of threat-related amygdala reactivity using fMRI as a predictive biomarker of risk for psychological vulnerability to stressful life events. The results of this study are consistent with previous studies that identify risk factors for depression and anxiety disorders in relation to increased amygdala reactivity to threat [54][55][56]. More research is required to implicate any neurobiological mechanisms of PTSD risk or resilience; however, identifying biomarkers and neuroimaging models for the purposes of diagnosis of PTSD would shift the paradigm from relying solely on self reported symptoms and help determine targets for pharmacologic treatment.…”

Section: Neurobiological Factorssupporting

confidence: 86%

Risk Factors for the Development of Psychopathology Following Trauma

Sayed

Iacoviello

Charney

2015

Curr Psychiatry Rep

119

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Traumatic experiences can lead to a range of mental health problems with posttraumatic stress disorder (PTSD) leading as the most documented disorder following trauma. Epidemiological research has found the rate of exposure to trauma to far outweigh the prevalence of PTSD. Indicating that most people do not develop PTSD following a traumatic event, this phenomenon has led to an interest in evaluating risk factors to determine who develops PTSD. Risk factors for the development of psychopathology following trauma exposure fall into three categories: pre-trauma, peri-trauma and post-trauma factors. Pre-trauma factors can include age, gender, race/ethnicity, education, prior psychopathology, and neurobiological factors. Peri-trauma factors can include the duration/severity of trauma experience and the perception that the trauma has ended. Post-trauma factors can include access to needed resources, social support, specific cognitive patterns, and physical activity. To date, several important risk factors have been found to impact the risk of developing PTSD including gender, age, education, IQ, race and ethnicity, sexual orientation, pre-trauma psychopathology, prior trauma exposure, familial psychiatric history, and neurobiological factors. This article outlines the state of research findings on pretraumatic, peritraumatic, and posttraumatic risk factors for the development of PTSD and associated psychopathology following trauma.

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Section: Neurobiological Factorssupporting

confidence: 86%

Risk Factors for the Development of Psychopathology Following Trauma

Sayed

Iacoviello

Charney

2015

Curr Psychiatry Rep

119

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“…The amygdala has also received widespread attention due to its involvement in emotion processing and response to aversive cues. Threat-related amygdala reactivity was associated with SLC6A4 methylation in two independent cohorts, including one in a longitudinal study where the increase in methylation after a 2 to 3 years of follow-up correlated to an increase in threat-related amygdala reactivity in the same time period (Nikolova et al, 2014;Swartz et al, 2016). Moreover, Muehlhan et al found the connectivity between the amygdala and key nodes of the salience network to be associated with SLC6A4 methylation (Muehlhan et al, 2015).…”

Section: Explanatory Variablesmentioning

confidence: 99%

An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR

Palma-Gudiel

Fañanás

2017

Neuroscience & Biobehavioral Reviews

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“…In addition, a number of studies have tried to correlate peripheral epigenetic changes with brain function using neuroimaging approaches. For example, increased promoter methylation of the serotonin transporter gene in peripheral blood predicted increased threat-related amygdala reactivity, and increased methylation of the same sites predicted decreased mRNA expression in post-mortem amygdala tissue (Nikolova et al, 2014). To date, however, the mechanistic insights from studies correlating peripheral epigenetic changes with brain imaging are limited.…”

Section: Epigenetic Modifications As a Potential Target Of Psychiatrimentioning

confidence: 99%

Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions

Klengel

Binder

2015

Neuron

283

184

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A deeper understanding of the pathomechanisms leading to stress-related psychiatric disorders is important for the development of more efficient preventive and therapeutic strategies. Epidemiological studies indicate a combined contribution of genetic and environmental factors in the risk for disease. The environment, particularly early life severe stress or trauma, can lead to lifelong molecular changes in the form of epigenetic modifications that can set the organism off on trajectories to health or disease. Epigenetic modifications are capable of shaping and storing the molecular response of a cell to its environment as a function of genetic predisposition. This provides a potential mechanism for gene-environment interactions. Here, we review epigenetic mechanisms associated with the response to stress and trauma exposure and the development of stress-related psychiatric disorders. We also look at how they may contribute to our understanding of the combined effects of genetic and environmental factors in shaping disease risk.

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Beyond genotype: serotonin transporter epigenetic modification predicts human brain function

Cited by 111 publications

References 29 publications

Risk Factors for the Development of Psychopathology Following Trauma

Risk Factors for the Development of Psychopathology Following Trauma

An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR

Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions

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