The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants

  title={The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants},
  author={Stephan K{\"o}hler and Katharina Cierpinsky and Golo Kronenberg and Mazda Adli},
  journal={Journal of Psychopharmacology},
  pages={13 - 22}
The monoamine hypothesis of depression posits that an imbalance in monoaminergic neurotransmission is causally related to the clinical features of depression. Antidepressants influencing serotonin mainly aim at raising serotonin concentrations, thereby increasing serotonergic transmission at the level of the synapse, for example by inhibiting the serotonin transporter. However, the serotonin system is multifaceted. Different serotonin receptor subtypes turn the serotonergic system into a… 

Tables from this paper

Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy

The emphasis is shifted from individual proteins to their interactions in explaining antidepressant action of SSRI, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance is discussed.

Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study

This study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist and offered functional information on the influence of pharmacological activation of 5-HT1A receptors in specific brain regions.

Novel Challenges for the Therapeutics of Depression: Pharmacological Modulation of Interaction between the Intracellular Signaling Pathways Mediated by Ca2+ and cAMP

The pharmacological modulation of this interaction by combined use of L-type CCBs, and cAMP-enhancer compounds, could be a more effi cient (and safer) therapeutic strategy to produce increase of serotoninergic and monoaminergic neurotransmission in the CNS due to enhance of serotonin and monoamines release, thus attenuating clinical symptoms of depression in humans.

Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

The evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5- HT regulates immune system signaling within the CNS and periphery is summarized.

The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter

Vilazodone is an antidepressant with limited information on its molecular interactions with SERT and it exhibits non-competitive inhibition of serotonin uptake and impedes dissociation of [3H]imipramine at low nanomolar concentrations.

Role of Estradiol in the Expression of Genes Involved in Serotonin Neurotransmission: Implications for Female Depression

Estradiol increases tryptophan hydroxylase-2 and serotonin transporter expression and decreases the expres-sion of serotonin 1A receptor and monoamine oxidase A and B through the interaction with its intracellular receptors.

The Therapeutic Prospects of Naturally Occurring and Synthetic Indole Alkaloids for Depression and Anxiety Disorders

The present review is a summary of the bioactive compounds from plants and marine sources that contain the indole moiety, which can serve as potent antidepressants.

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.



Review: The auspicious role of the 5-HT3 receptor in depression: a probable neuronal target?

Behavioural, neurochemical, electrophysiological and molecular analyses, including the results from the laboratory, provided substantial evidence that rationalizes the correlation between serotonin type-3 receptor modulation and rodent depressive-like behaviour.

The 5-HT1B receptor: a novel target for the pathophysiology of depression.

A review of the literature provides strong evidence that 5-HT(1B) receptors and related factors such as p11 are involved in the pathophysiology of depression, and possible factors which may render the 5- HT( 1B) receptor dysfunctional, resulting in susceptibility to depression are explored.

Serotonin 5-HT1A Receptors as Targets for Agents to Treat Psychiatric Disorders: Rationale and Current Status of Research

In agreement with pharmacological studies, presynaptic and postsynaptic 5- HT1A-R activation appears necessary for anxiolytic and antidepressant effects, respectively, yet, neurodevelopmental roles for 5-HT 1A-Rs are also involved.

Modulating the serotonin system in the treatment of major depressive disorder

How pharmacologic interventions, including novel and existing antidepressants and atypical antipsychotics, may be utilized to adjust serotonergic neurotransmission and provide more effective treatments for patients with MDD are discussed.

Triple reuptake inhibitors for treating subtypes of major depressive disorder: the monoamine hypothesis revisited

This article reviews the development of new broad-spectrum antidepressants, the triple reuptake inhibitors, which also increase brain dopamine levels and proposes a hypothetical model: ‘the monoamine hypothesis revisited’ to predict what kind of pharmacological treatment will be effective in the different subtypes of depression.

The 5-HT7 receptor and disorders of the nervous system: an overview

  • P. Hedlund
  • Psychology, Medicine
  • 2009
The use of pharmacological and genetic tools in preclinical animal models strongly supports a role for the 5-HT7 receptor in depression and indirect evidence exists showing that 5- HT7 receptor antagonism is clinically useful in the treatment of depression.

Relationship of neurotransmitters to the symptoms of major depressive disorder.

  • D. Nutt
  • Psychology
    The Journal of clinical psychiatry
  • 2008
A 2-dimensional model of neurotransmitter functions is discussed that describes depression as a mixture of 2 separate components--negative affect and the loss of positive affect--that can be considered in relation to the 3 amine neurotransmitters.

Serotonergic drugs for depression and beyond.

Various strategies that build upon SERT inhibition provide promise for novel therapeutic approaches to depression, including the possibility of targeting residual symptoms not well treated by Sert inhibition alone, and reducing side effects, such as sexual dysfunction.

Clinical utility of vilazodone for the treatment of adults with major depressive disorder and theoretical implications for future clinical use

As a new option for the treatment of major depressive disorder, vilazodone, due to its unique SPARI mechanism of action, may hold promise for patients who cannot tolerate or have not responded to previous antidepressant monotherapies.