Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

Holmes, Andrew

doi:10.1016/j.neubiorev.2008.03.006

Cited by 239 publications

(177 citation statements)

References 481 publications

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“…The lack of functional serotonin transporter at early developmental stages leads to a lifelong phenotype of anxiety-like and depression-like behaviours in novel environments. 44,46,47 This lasting effect is mediated by increased extracellular serotonin during the plastic early developmental period and subsequent downregulation and desensitization of the inhibitory 5-HT1A receptors. 46 A less pronounced reduction in the serotonin reuptake due to presence of 5-HTTLPR low expressing alleles may lead to similar consequences only in the presence of increased serotonin efflux, due to stress in the early developmental period.…”

Section: Beneath the Surface: Molecular Mechanismsmentioning

confidence: 99%

“…48,51 Without the balancing effect of the efficient 5-HTTLPR long allele, this programming increases stress-sensitivity and anxiety in response to novelty in adult life. 7,44,47 This programming may have an adaptive function: if early stress predicts dangerous conditions in later life, it may be advantageous to enhance self-protective functions at the expense of exploratory behaviour.…”

Section: Beneath the Surface: Molecular Mechanismsmentioning

confidence: 99%

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The implications of gene–environment interactions in depression: will cause inform cure?

Uher

2008

Mol Psychiatry

131

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In a number of human diseases, including depression, interactions between genetic and environmental factors have been identified in the absence of direct genotype-disorder associations. The lack of genes with major direct pathogenic effect suggests that genotype-specific vulnerabilities are balanced by adaptive advantages and implies aetiological heterogeneity. A model of depression is proposed that incorporates the interacting genetic and environmental factors over the life course and provides an explanatory framework for the heterogeneous aetiology of depression. Early environmental influences act on the genome to shape the adaptability to environmental changes in later life. The possibility is explored that genotype-and epigenotype-related traits can be harnessed to develop personalized therapeutic interventions. As diagnosis of depression alone is a weak predictor of response to specific treatments, aetiological subtypes can be used to inform the choice between treatments. As a specific application of this notion, a hypothesis is proposed regarding relative responsiveness of aetiological subtypes of depression to psychological treatment and antidepressant medication. Other testable predictions are likely to emerge from the general framework of interacting genetic, epigenetic and environmental mechanisms in depression.

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Section: Beneath the Surface: Molecular Mechanismsmentioning

confidence: 99%

Section: Beneath the Surface: Molecular Mechanismsmentioning

confidence: 99%

The implications of gene–environment interactions in depression: will cause inform cure?

Uher

2008

Mol Psychiatry

131

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“…Thus, estrogen and the amygdala are closely related [8]. Furthermore, the amygdala expresses 5-HT receptors (5-HT1-7) and receives serotonergic input from the raphe [2,[16][17][18][19][20][21][22][23][24][25][26]. Therefore, estrogen and its moderators may be effective treatment methods for OVX-induced depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

MU314, a novel selective estrogen receptor modulator (SERM), improves estrogen-dependent depressive behaviors

Izumo¹,

Ishibashi²,

Ono³

et al. 2017

Glob Drugs Therap

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“…The 1A serotonin receptors (5-HT1A) are not expressed in BLA neurons, but are expressed in the raphe axon terminals targeting the BLA, where they act as autoreceptors and modulate serotonergic release in the BLA. Activation of these receptors limits the release of serotonin at nerve terminals and affects overall serotonergic tone (for review, see Holmes 2008).…”

Section: Dorsal Raphe Nuclei Projections To the Blamentioning

confidence: 99%

“…5-HT1A agonists infused into the BLA impair the expression of context fear conditioning (Stiedl et al 2000;Li et al 2006) and decrease the acquisition and expression of a conditioned defeat task (Morrison and Cooper 2012). The role of 5-HT1A receptors in anxiety is unclear, since 5-HT1A agonists applied into the rat BLA can both reduce and increase anxiety (Holmes 2008). These results may be explained by differential effects of 5-HT1A agonists on BLA neuronal activity.…”

Section: Dorsal Raphe Nuclei Projections To the Blamentioning

confidence: 99%

Input-specific contributions to valence processing in the amygdala

Correia

Goosens

2016

Learn. Mem.

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Reward and punishment are often thought of as opposing processes: rewards and the environmental cues that predict them elicit approach and consummatory behaviors, while punishments drive aversion and avoidance behaviors. This framework suggests that there may be segregated brain circuits for these valenced behaviors. The basolateral amygdala (BLA) is one brain region that contributes to both types of motivated behavior. Individual neurons in the BLA can favor positive over negative valence, or vice versa, but these neurons are intermingled, showing no anatomical segregation. The amygdala receives inputs from many brain areas and current theories posit that encoding of positive versus negative valence by BLA neurons is determined by the wiring of each neuron. Specifically, many projections from other brain areas that respond to positive and negative valence stimuli and predictive cues project strongly to the BLA and likely contribute to valence processing within the BLA. Here we review three of these areas, the basal forebrain, the dorsal raphe nucleus and the ventral tegmental area, and discuss how these may promote encoding of positive and negative valence within the BLA.The basic desire to seek reward and avoid punishment shapes virtually all of behavior, and the ability to discriminate between "good" and "bad" environmental cues is critical for guiding choices and maximizing survival. Thus, understanding the brain circuits that encode motivated behaviors is important because it contributes to our knowledge of how we learn, and it is also essential for understanding human disorders associated with abnormal processing of reward and danger (i.e., emotional disorders), such as anxiety, depression, addiction, and post-traumatic stress disorder (PTSD).The amygdala is one brain area implicated in motivated behaviors and the basolateral complex of the amygdala (BLA) receives information about diverse environmental stimuli from many brain regions. The BLA is thought to encode the association of predictive stimuli with both aversive and appetitive outcomes (Morrison and Salzman 2010;Barberini et al. 2012). Reward and punishment are reinforcers of opposite valence (positive versus negative), and these reinforcers typically lead to opposing behaviors (approach versus avoidance). Many theories have suggested that appetitive and aversive systems act in opponent fashion (Solomon and Corbit 1974;Daw et al. 2002). However, it is unclear how the BLA contributes to this. We do not yet understand the extent to which aversive and appetitive information is processed in parallel BLA circuits, or whether individual BLA neurons are involved in the regulation of both types of motivated behaviors.In this review, we propose several models by which functional segregation of valence can be achieved in the BLA. These models are based on studies describing how BLA neurons respond to reward and aversive stimuli. We then consider whether three major inputs, known to carry valenced information, support or conflict these models, and also discus...

show abstract

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

Cited by 239 publications

References 481 publications

The implications of gene–environment interactions in depression: will cause inform cure?

The implications of gene–environment interactions in depression: will cause inform cure?

MU314, a novel selective estrogen receptor modulator (SERM), improves estrogen-dependent depressive behaviors

Input-specific contributions to valence processing in the amygdala

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