The developmental role of serotonin: news from mouse molecular genetics

Gaspar, Patricia; Cases, Olivier; Maroteaux, Luc

doi:10.1038/nrn1256

Cited by 1,169 publications

(1,001 citation statements)

References 136 publications

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“…In addition, our understanding of the use of fluoxetine is limited to noninstitutionalized outpatients and only children 5-years and older. Future studies should focus on institutionalized and noninstitutionalized patients, as well as younger children, since SSRIs may promote neurogenesis (Gaspar et al, 2003) and differentiation factors in early brain development. This study focused on repetitive behaviors; future studies should assess in a more specific manner possible improvements in the other core deficits in social and communication function.…”

Section: Discussionmentioning

confidence: 99%

A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Hollander

Phillips

Chaplin

et al. 2004

Neuropsychopharmacol

353

214

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Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebocontrolled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.974.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

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Section: Discussionmentioning

confidence: 99%

A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Hollander

Phillips

Chaplin

et al. 2004

Neuropsychopharmacol

353

214

View full text Add to dashboard Cite

show abstract

“…The serotonergic projections innervate multiple cortical brain regions to regulate a wide repertoire of behaviors, as well as cognition and mood. In addition to its prominent role as a neurotransmitter, 5-HT plays an important role in brain development via regulation of neurite outgrowth, synaptogenesis, and cell survival (Gaspar et al, 2003). In the adult, serotonergic neurotransmission modulates many brain functions including emotion, cognition, motor function, and pain sensitivity.…”

Section: Bdnfmentioning

confidence: 99%

Interaction between BDNF and Serotonin: Role in Mood Disorders

Martinowich

2007

Neuropsychopharmacol

686

458

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Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are two seemingly distinct signaling systems that play regulatory roles in many neuronal functions including survival, neurogenesis, and synaptic plasticity. A common feature of the two systems is their ability to regulate the development and plasticity of neural circuits involved in mood disorders such as depression and anxiety. BDNF promotes the survival and differentiation of 5-HT neurons. Conversely, administration of antidepressant selective serotonin reuptake inhibitors (SSRIs) enhances BDNF gene expression. There is also evidence for synergism between the two systems in affective behaviors and genetic epitasis between BDNF and the serotonin transporter genes.

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“…127 The 5-HTergic system develops early in the mammalian brain and is widespread, therefore it can influence the maturation of many other cells in the brain. 168 In addition to influencing the development of target regions, 5-HT also has a negative feedback effect on the developing fetal 5-HT neurons. 169 As 5-HT neurons develop, 5-HT levels increase until a point is reached at which the growth is curtailed through a negative feedback mechanism.…”

Section: Stressmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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The developmental role of serotonin: news from mouse molecular genetics

Cited by 1,169 publications

References 136 publications

A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Interaction between BDNF and Serotonin: Role in Mood Disorders

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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