Role of 5-HT in stress, anxiety, and depression

Graeff, Frederico Guilherme; Guimarães, Francisco Silveira; Andrade, Telma Gonçalves Carneiro Spera de; Deakin, J. F. William

doi:10.1016/0091-3057(95)02135-3

Cited by 865 publications

(509 citation statements)

References 87 publications

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“…There is abundant empirical evidence implicating 5-HT in controlling aversion and potentiating anxiety-induced avoidance (Tye et al, 1977;Gray, 1982;Graeff et al, 1996). The hypothesis concurs with the observation that serotonergic neurotransmission is implicated in a range of mood and anxiety disorders (Young et al, 1985;Anderson et al, 1990;Deakin et al, 1990;Blier and de Montigny, 1999) that are characterized by enhanced anticipation of, and sensitivity to threat-related stimuli, punishment, and negative feedback (Beats et al, 1996;Elliott et al, 1997;Mathews and Mackintosh, 2000;Steffens et al, 2001;Richards et al, 2002;Murphy et al, 2003).…”

Section: Introductionsupporting

confidence: 57%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

149

152

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Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishmentassociated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

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Section: Introductionsupporting

confidence: 57%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

149

152

View full text Add to dashboard Cite

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“…A key mechanism of action of antidepressant agents is to enhance the efficacy of 5-HT neurotransmission, which occurs following chronic treatment. In the hippocampus, this would restore the capacity to tolerate chronic stress (for reviews of this topic and original references, see references [20][21] ).…”

Section: Anxietymentioning

confidence: 99%

Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal

Graeff

2007

Rev. Bras. Psiquiatr.

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A b s t r a c t Objective: This article focuses on the differential activation of the hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic disorder. Method: The results of recently reported reviews of the literature are summarized and discussed. Results: The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks, as well as those induced by selective panicogenic agents such as lactate and carbon dioxide, do not activate the hypothalamic-pituitary-adrenal axis. Agonists of the cholecystokinin receptor B such as the cholecystokinin-4 peptide and pentagastrin increase stress hormones regardless of the occurrence of a panic attack and, thus, seem to activate the hypothalamicpituitary-adrenal axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increase anxiety in both normal people and panic patients (caffeine, yohimbine, serotonergic agonists) raise stress hormone levels. Conclusions: In addition to the differences in symptomatology and pharmacological response, generalized anxiety disorder and panic disorder affect stress hormones in distinct ways. While anticipatory anxiety and generalized anxiety disorder activate both the hypothalamic-pituitary-adrenal and the sympathoadrenal axes, panic attack causes major sympathetic activation, but has little effect on the hypothalamic-pituitaryadrenal axis.Descriptors: Stress; Hormones; Anxiety disorders; Hypothalamus; Pituitary-adrenal system Resumo Objetivo: Este artigo discute a ativação diferencial do eixo hipotálamo-pituitária-adrenal no transtorno de ansiedade generalizada e no transtorno de pânico. Método: Resultados de recentes revisões da literatura são resumidos e discutidos. Resultados: Os resultados de estudos experimentais que dosaram o hormônio adrenocorticotrópico, o cortisol e a prolactina mostram que ataques de pânico espontâneos, bem como os provocados por agentes panicogênicos seletivos -como lactato de sódio e dióxido de carbono -, não ativam o eixo hipotálamo-pituitária-adrenal. Agonistas do receptor de colecistocinina do tipo B, como o peptídeo colecistocinina-4 e pentagastrina, elevam os hormônios de estresse, independentemente da ocorrência de um ataque de pânico, parecendo ativar diretamente o eixo hipotálamo-pituitária-adrenal. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse; porém, este agente farmacológico não induz ataques de pânico de modo consistente. Agentes farmacológicos que aumentam a ansiedade em pacientes de pânico (cafeína, ioimbina, agonistas serotonérgicos), assim como em pessoas saudáveis, elevam o nível dos hormônios de estresse. Conclusões: Além das diferenças na sintomatologia e na resposta farmacológica, o transtorno de ansiedade generalizada e o transtorno de pânico afetam os hormônios de estresse de modo distinto. Enquanto a ansiedade antecipatória e o transtorno de ansied...

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“…[5][6][7] 5-HT is synthesized within the brain from the essential amino acid tryptophan (TRP). Other amino acids, notably tyrosine, valine, phenylalanine, leucine and isoleucine, affect 5-HT precursor availability by competing with TRP for transport across the blood-brain barrier (BBB) and are also referred to as competing amino acids (CAA).…”

mentioning

confidence: 99%

IDO and interferon-α-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity

et al. 2004

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Studies show that administration of interferon (IFN)-a causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-a-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-a treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-a treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-a-induced depressive symptoms, through its induction of neurotoxic KYN metabolites. Molecular Psychiatry (2005) 10, 538-544.

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Role of 5-HT in stress, anxiety, and depression

Cited by 865 publications

References 87 publications

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal

IDO and interferon-α-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity

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