Serotonin 5-HT2A receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression

Benedetti, Francesco; Barbini, Barbara; Bernasconi, Alessandro; Fulgosi, Mara Cigala; Colombo, Cristina; Dallaspezia, Sara; Gavinelli, Chiara; Marino, Elena; Pirovano, Adele; Radaelli, Daniele; Smeraldi, Enrico

doi:10.1016/j.pnpbp.2008.08.017

Cited by 34 publications

(15 citation statements)

References 22 publications

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“…Biological factors affecting the activity of these pathways, such as genotypic variants [51,[135][136][137] , basal neurotransmitter levels [138] , or the extent of receptor occupancy [139] , affect the clinical response, thus confirming a critical role for changes in monoaminergic neurotransmission in the clinical effect of SD.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Sleep Deprivation in Mood Disorders

2011

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Growing clinical evidence in support of the efficacy and safety of sleep deprivation (SD), and its biological mechanisms of action suggest that this technique can now be included among the first-line antidepressant treatment strategies for mood disorders. SD targets the broadly defined depressive syndrome, and can be administered according to several different treatment schedules: total versus partial, single versus repeated, alone or combined with antidepressant drugs, mood stabilizers, or other chronotherapeutic techniques, such as light therapy and sleep phase advance. The present review focuses on clinical evidence about the place of SD in therapy, its indications, dosage and timing of the therapeutic wake, interactions with other treatments, precautions and contraindications, adverse reactions, mechanism of action, and comparative efficacy, with the aim of providing the clinical psychiatrist with an updated, concise guide to its application.

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Section: Mechanism Of Actionmentioning

confidence: 99%

Sleep Deprivation in Mood Disorders

2011

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“…A common denominator of serotonin-based hallucinogens is their high affinity for serotonin type 2 (5-HT 2 ) receptors (Nichols 2004), including 5-HT 2A and 5-HT 2C receptors that are expressed densely in regions of the brain known to regulate emotion and memory, such as the frontal cortex and limbic structures (Lopez-Gimenez et al 1997, 2001, 2002). 5-HT 2A and 5-HT 2C receptors are altered in psychiatric conditions, ranging from obsessive-compulsive disorder and depression (Benedetti et al 2008; Millan 2005) to schizophrenia (Herrick-Davis et al 2000; Kang et al 2009; Quednow et al 2009). In addition, atypical antipsychotics as well as novel antidepressants and anxiolytic medications target 5-HT 2A and/or 5-HT 2C receptors.…”

Section: Introductionmentioning

confidence: 99%

The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen

et al. 2010

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Rationale Hallucinogenic serotonin 2A (5-HT2A) receptor partial agonists, such as (±)-1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane hydrochloride (DOI), induce a frontal cortex-dependent head-twitch response (HTR) in rodents, a behavioral proxy of a hallucinogenic response that is blocked by 5-HT2A receptor antagonists. In addition to 5-HT2A receptors, DOI and most other serotonin-like hallucinogens have high affinity and potency as partial agonists at 5-HT2C receptors. Objectives We tested for involvement of 5-HT2C receptors in the HTR induced by DOI. Results Comparison of 5-HT2C receptor knockout and wild-type littermates revealed an approximately 50% reduction in DOI-induced HTR in knockout mice. Also, pretreatment with either the 5-HT2C receptor antagonist SB206553 or SB242084 eradicated a twofold difference in DOI-induced HTR between the standard inbred mouse strains C57BL/6J and DBA/2J, and decreased the DOI-induced HTR by at least 50% in both strains. None of several measures of 5-HT2A receptors in frontal cortex explained the strain difference, including 5-HT2A receptor density, Gαq or Gαi/o protein levels, phospholipase C activity, or DOI-induced expression of Egr1 and Egr2. 5-HT2C receptor density in the brains of C57BL/6J and DBA/2J was also equivalent, suggesting that 5-HT2C receptor-mediated intracellular signaling or other physiological modulators of the HTR may explain the strain difference in response to DOI. Conclusions We conclude that the HTR to DOI in mice is strongly modulated by 5-HT2C receptor activity. This novel finding invites reassessment of hallucinogenic mechanisms involving 5-HT2 receptors.

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“…There are certain genes that have been implicated in an increased susceptibility to depression in non‐CFS patients 34 . Among them, a low amount of serotonin receptor density encoded in the prefrontal cortex has been associated with depression and suicide 35 . Serotonin receptor polymorphisms have been associated with receptor‐binding potential, with the ability of individuals to use environmental support in order to prevent depression and with sleep improvement after antidepressant treatment 34,35 …”

Section: Discussionmentioning

confidence: 99%

“…34 Among them, a low amount of serotonin receptor density encoded in the prefrontal cortex has been associ-ated with depression and suicide. 35 Serotonin receptor polymorphisms have been associated with receptor-binding potential, with the ability of individuals to use environmental support in order to prevent depression and with sleep improvement after antidepressant treatment. 34,35 During univariate analyses, we found that the serotonin receptor AA genotype was a risk factor for depressive symptoms among CFS patients; in spite of this, after adjustments for confounding factors, the AG genotype was found to be associated with protection against depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome

Ortega-Hernandez

Cuccia

Beigrezaei

et al. 2009

Annals of the New York Academy of Sciences

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This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS) onset and symptoms. Eighty-one CFS patients were enrolled, and clinical data were recorded. Autoantibodies to different components of the central nervous system were tested. Polymorphisms in the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the serotonin receptor-2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic-regression analyses were carried out. The mean age at CFS onset +/- SD was 33.5 +/- 12.5 years. An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA-DRB1*07 allele, whereas an ACFSO > or = 43 years was associated with having at least one copy of the serotonin G allele. Concerning CFS symptoms, the serotonin AG genotype was protective against depressive symptoms. Although having at least one copy of the serotonin A allele and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies was protective against this. Episodes of unexplained fever were associated with the HLA-DRB1*11 allele. None of the genetic or serological features was associated with myalgia. None of the antibodies determined correlated with any ACFSO or other symptoms. Our results reveal that in CFS, like other autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.

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Serotonin 5-HT2A receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression

Cited by 34 publications

References 22 publications

Sleep Deprivation in Mood Disorders

Sleep Deprivation in Mood Disorders

The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen

Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome

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