Serotonin and Stress

Chaouloff, Francis; Berton, Olivier; Mormède, Pierre

doi:10.1016/s0893-133x(99)00008-1

Cited by 223 publications

(93 citation statements)

References 35 publications

(45 reference statements)

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“…Signals are carried throughout the body by the sequential firing of one neuron after another across these synapses. When an individual experiences stress, it causes increased neuron activity, stimulating the release of excess serotonin into the gaps between the synapses (Chaouloff, Berton, and Mormede 1999). If serotonin remains outside the cells, it can oxidize into a toxin that kills both the presynaptic and postsynaptic neurons.…”

Section: Serotonin Genes and Social Behaviormentioning

confidence: 99%

Two Genes Predict Voter Turnout

Fowler

Dawes

2008

The Journal of Politics

216

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Fowler, Baker, and Dawes (2008) recently showed in two independent studies of twins that voter turnout has very high heritability. Here we investigate two specific genes that may contribute to variation in voting behavior. Using data from the National Longitudinal Study of Adolescent Health, we show that individuals with a polymorphism of the MAOA gene are significantly more likely to have voted in the 2004 presidential election. We also find evidence that an association between a polymorphism of the 5HTT gene and voter turnout is moderated by religious attendance. These are the first results ever to link specific genes to political behavior. Social scientists have shown that basic political attitudes like liberalism and conservatism are likely to be heritable (Alford, Funk, and Hibbing 2005, Hatemi et al. 2007). While the choice of a particular candidate or party does not appear to be heritable, a significant proportion of the variation in the decision to participate in politics can be attributed to genetic factors. Fowler, Baker, and Dawes (2008) recently studied the voting behavior of two populations of twins and showed that heritability accounted for 53% of the variation in validated turnout of those living in Los Angeles county and 72% of the self-reported turnout in a nationally representative sample of young adults. They also showed that heritability accounted for 60% of the variation in a general index of political participation, including contributing to campaigns, running for office, volunteering for political organizations, and attending protests. These results were the first to suggest that humans exhibit inherent variability in their willingness to participate in politics.However, these initial results based on twin studies beg the question ''which genes?'' The natural place to start the search for such genes is among those that have already been shown to account for variation in social behavior. And among these, MAOA and 5HTT are prime candidates. These two genes transcribe neurochemicals that exert a strong influence on the serotonin system in parts of the brain that regulate fear, trust, and social interaction (Bertolino et al. 2005; Eisenberger et al. 2007;Hariri et al. 2002;Hariri et al. 2005;Heinz et al. 2005;Meyer-Lindenberg et al. 2006). MAOA and 5HTT have been studied for more than 20 years, and much is known about the way different versions of their genes regulate transcription, metabolism, and signal transfers between neurons, all of which have an effect on social interactions (Craig 2007). In particular, the less transcriptionally efficient alleles of these genes have been associated with a variety of antisocial behaviors (Rhee and Waldman 2002).In this article, we hypothesize that people with more transcriptionally efficient alleles of the MAOA and 5HTT genes are more likely to vote. An association between a gene and political behavior may also be moderated by environmental factors. This phenomenon is known as a gene-environment (GxE) interaction (Shanahan and Hofer 2005). We therefore...

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Section: Serotonin Genes and Social Behaviormentioning

confidence: 99%

Two Genes Predict Voter Turnout

Fowler

Dawes

2008

The Journal of Politics

216

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“…Some consider serotonin to function mainly in a tonic steady-state mode of activity also related primarily to behavioral arousal (Rueter and Jacobs, 1996), although this relationship can be modified (Chaouloff et al, 1999). Others, though, consider that even if there is some constant tonic level of serotonergic activity, there can still be local modulation of serotonin release that may be both brain region and stimulus specific (Kirby et al, 1995(Kirby et al, , 1997.…”

Section: Drug-induced Effects On Monoamines and Behavioral Changesmentioning

confidence: 99%

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Katz

Tekell

Bowden

et al. 2003

Neuropsychopharmacol

234

153

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This study was aimed at resolving the time course of clinical action of antidepressants (ADs) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients. The first goal was to identify, during the first 2 weeks of treatment, the onset of clinical actions of the selective serotonin reuptake inhibitor (SSRI), paroxetine, and the selective noradrenergic reuptake inhibitor, desipramine (DMI). The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients. The design was a randomized, parallel group, placebo-controlled, double-blind study for 6 weeks of treatment following a 1-week washout period. The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity. The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days, averaged 13 days for paroxetine, and was 16-42 days for placebo. Furthermore, as hypothesized, the different types of ADs initially impacted different behavioral aspects of the disorder. After 1 week of treatment, DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo, and this difference persisted at the second week of treatment. Early improvement in depressed mood-motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not. Paroxetine initially reduced anxiety more in responders than in nonresponders, and by the second week, significantly improved depressed mood and distressed expression in responders to a greater extent. Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement. Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs, results that could eventually be applied directly to clinical practice.

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“…Although serotonin is well known to modulate a variety of physiological and behavioral processes including sleep-wake cycles, and circadian rhythms, the effect of valerian on serotonin receptor binding has not been completely elucidated [9,24]. Serotonin (5-HT, 5-hydroxytryptamine) impacts numerous sensory, motor, and cortical functions by activating multiple 5-HT receptor subtypes [9,24,35].…”

Section: Introductionmentioning

confidence: 99%

“…Serotonin (5-HT, 5-hydroxytryptamine) impacts numerous sensory, motor, and cortical functions by activating multiple 5-HT receptor subtypes [9,24,35]. Abnormalities of these receptor systems have been implicated in many psychiatric disorders including anxiety, depression, as well as disorders of cognition, stress, and sleep [9,28,35]. Serotonin was initially thought to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chloro-phenylalanine induced severe insomnia that could be reversed by restoring 5-HT synthesis [2].…”

Section: Introductionmentioning

confidence: 99%

“…Serotonin was initially thought to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chloro-phenylalanine induced severe insomnia that could be reversed by restoring 5-HT synthesis [2]. More recent experiments suggest that the release of 5-HT during the sleep-wakefulness cycle initiates a cascade of genomic events in some hypnogenic neurons located in the preoptic area and the neighboring suprachiasmatic nucleus including vasoactive intestinal polypeptide and GABAergic mechanism [1,3,9,15,28,35].…”

Section: Introductionmentioning

confidence: 99%

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Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro

Dietz

Mahady

Pauli

et al. 2005

Molecular Brain Research

126

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Insomnia is the most frequently encountered sleep complaint worldwide. While many prescription drugs are used to treat insomnia, extracts of valerian (Valeriana officinalis L., Valerianaceae) are also used for the treatment of insomnia and restlessness. To determine novel mechanisms of action, radioligand binding studies were performed with valerian extracts (100% methanol, 50% methanol, dichloromethane [DCM], and petroleum ether [PE]) at the melatonin, glutamate, and GABA A receptors, and 8 serotonin receptor subtypes. Both DCM and PE extracts had strong binding affinity to the 5-HT 5a receptor, but only weak binding affinity to the 5-HT 2b and the serotonin transporter. Subsequent binding studies focused on the 5-HT 5a receptor due to the distribution of this receptor in the suprachiasmatic nucleus of the brain, which is implicated in the sleep-wake cycle. The PE extract inhibited [ 3 H]lysergic acid diethylamide (LSD) binding to the human 5-HT 5a receptor (86% at 50 μg/ml) and the DCM extract inhibited LSD binding by 51%. Generation of an IC 50 curve for the PE extract produced a biphasic curve, thus GTP shift experiments were also performed. In the absence of GTP, the competition curve was biphasic (two affinity sites) with an IC 50 of 15.7 ng/ml for the high-affinity state and 27.7 μg/ml for the lowaffinity state. The addition of GTP (100 AM) resulted in a right-hand shift of the binding curve with an IC 50 of 11.4 μg/ml. Valerenic acid, the active constituent of both extracts, had an IC 50 of 17.2 AM. These results indicate that valerian and valerenic acid are new partial agonists of the 5-HT 5a receptor.

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Serotonin and Stress

Cited by 223 publications

References 35 publications

Two Genes Predict Voter Turnout

Two Genes Predict Voter Turnout

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro

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