Human amygdala volume is predicted by common DNA variation in the stathmin and serotonin transporter genes

Stjepanović, Daniel; Lorenzetti, Valentina; Yücel, Murat; Hawi, Ziarih; Bellgrove, Mark A.

doi:10.1038/tp.2013.41

Cited by 11 publications

(8 citation statements)

References 81 publications

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“…Overall, these findings indicate that increasing serotonin level is associated with reduced activity in this circuitry, particularly in the amygdala, to threat-related stimuli (although see references 31, 32), while decreasing serotonin level is associated with increased functioning within this circuitry (33, 34). Furthermore, there is evidence indicating an impact of genetic variation in 5-HTTLPR and other genes affecting serotonergic functioning on amygdala and hippocampal volumes (35–37). A smaller number of studies indicate that other neurotransmitters, for example, catecholamines such as norepinephrine, may also modulate functioning in this circuitry (20, 38, 39).…”

Section: Neural Circuits Underlying Implicit Emotion Regulation and Rmentioning

confidence: 99%

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

Phillips¹,

Chase²,

Sheline³

et al. 2015

AJP

215

165

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Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.

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Section: Neural Circuits Underlying Implicit Emotion Regulation and Rmentioning

confidence: 99%

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

Phillips¹,

Chase²,

Sheline³

et al. 2015

AJP

215

165

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“…Larger amygdala volume has also been associated with traits similar to inhibited temperament, including fearfulness (van der Plas et al, 2010), sensitivity to punishment (Barros-Loscertales et al, 2006), and harm avoidance (Iidaka et al, 2006). Several recent studies suggest that amygdala volume may be related to certain genes associated with anxiety vulnerability (Haaker et al, 2014; Mueller et al, 2013; Stjepanović et al, 2013); however, more studies are needed to replicate these findings. The causes of larger amygdala volumes in inhibited individuals remain unclear, although increased synaptogenesis, increased neuron number, or increased glia number are all likely mechanisms.…”

Section: Neural Basis Of Inhibited Temperamentmentioning

confidence: 99%

The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis

Clauss

Avery

Blackford

2015

Progress in Neurobiology

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What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences—the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease.

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“…The detailed measurement of cannabis variables (age of onset of regular use, lifetime cumulative dose or dose change) in the examined cannabis group allowed us to study the influence of potential mediating variables, including cannabis dose and age of onset. Last, the use of manual tracing has the benefit of enhanced sensitivity to subtle effects in hippocampal shape and greater precision in detecting inter-individual variability in anatomical boundaries when compared to the application of automated protocols ( Stjepanovic et al, 2013 ). Manual tracing also allows shape analyses, enabling the examination of whether cannabis use affects specific hippocampal subregions ( Gilman et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…We decided to study the hippocampal region in more detail using manual tracing of the hippocampus in the same sample. The use of a manual tracing technique by an experienced tracer has the benefit of enhanced sensitivity to subtle effects in hippocampal shape and greater precision in detecting inter-individual variability in anatomical boundaries when compared to the application of automated protocols such as VBM ( Stjepanovic et al, 2013 ). Manual tracing also allows shape analyses, enabling examination of whether cannabis use affects specific hippocampal sub regions ( Gilman et al, 2014 ; Gogtay et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of hippocampal volumes in heavy cannabis users

et al. 2017

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Background:Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes.Methods:Twenty heavy cannabis users (mean age 21 years, range 18–24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol.Results:Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes.Conclusions:Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

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Human amygdala volume is predicted by common DNA variation in the stathmin and serotonin transporter genes

Cited by 11 publications

References 81 publications

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis

Longitudinal study of hippocampal volumes in heavy cannabis users

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