The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

Попова, Н. К.; Цыбко, А. С.; Науменко, В. С.

doi:10.3390/ijms23158814

Cited by 36 publications

(23 citation statements)

References 262 publications

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“…In general agreement with previous reports, patients with anxiety depression had a higher frequency of major depressive episodes and a higher risk of suicidal ideation and previous suicide attempts compared to patients with non-anxiety depression [24,39]. A review explains the functional characteristics and nature of 5-HT receptor involvement in the regulation of pathological behavior, highlighting the role of 5-HT receptors in behavioral conditions such as suicide, depression, and anxiety [40].…”

Section: Differences Between Clinical Subgroups With and Without Anxietysupporting

confidence: 87%

Prevalence and correlates of severe anxiety in patients with first hospitalization for major depressive disorder combined with dyslipidemia: a large sample cross-sectional study

Yin

Zhang

Liu³

et al. 2023

Preprint

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Background: Anxiety symptoms and dyslipidemia are common comorbidities in patients with major depressive disorder (MDD), and there are complex pathophysiologic as well as clinical mechanisms underlying the association between the three. In this study, we investigated the prevalence and associated factors of severe anxiety in first-time hospitalized patients with MDD with dyslipidemia. Methods: We included 708 patients with major depressive disorder with comorbid dyslipidemia and collected their sociodemographic and general clinical data as well as biochemical parameters such as lipids, thyroid function and blood glucose. We also completed the Hamilton Anxiety Scale (HAMD), Hamilton Depression Scale (HAMD), Positive Symptom Scale (PSS) and Clinical General Impression Scale (CGI) to assess their clinical symptoms. Results: The prevalence of severe anxiety disorder in MDD patients with dyslipidemia combined with first hospitalization was 11. 02%. HAMD score, PSS score, history of suicide, body mass index (BMI), thyroid-stimulating hormone (TSH) level, and tetra-iodothyronine (FT4) level were the risk factors for the development of severe anxiety disorders in patients with MDD who were comorbid with dyslipidemia. Higher HAMD scores and TSH level may exacerbate the development of severe anxiety symptoms. Conclusion: This study reports and identifies the prevalence of anxiety symptoms in first-time hospitalized MDD patients with comorbid dyslipidemia, as well as risk factors for anxiety symptoms and severity of anxiety symptoms, and these identified factors may be potentially useful and informative for preventing and intervening in severe anxiety in this target population.

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Section: Differences Between Clinical Subgroups With and Without Anxietysupporting

confidence: 87%

Prevalence and correlates of severe anxiety in patients with first hospitalization for major depressive disorder combined with dyslipidemia: a large sample cross-sectional study

Yin

Zhang

Liu³

et al. 2023

Preprint

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“…Patients with treatment-resistant anxiety represent a significant ongoing challenge and underscore the necessity for novel treatment methodologies. Targeting the down-regulation of 5HT-2A receptors constitutes a rational approach based on the mechanism of action of current medications ( 7 , 9 ). In the present study, we show that delivery of copackaged Cas9 DNA with a Htr2a-targeting gRNA led to a sharp increase in indel formation and decreased neuronal electrical activity in vitro without any observable toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we investigated whether intranasal delivery of CRISPR/Cas9 could bypass the BBB and lead to knockout of the HTR2A gene in neuronal populations ( PCT/US2022/050947I ). The 5HT-2A receptor is implicated in both anxiety and depression disorders ( 7–10 ), and current legacy treatments with selective serotonin reuptake inhibitor (SSRI) compounds are fraught with side effects, show low efficacy, and require daily dosing ( 11 , 12 ). Therefore, there is a pressing need for newer, more effective therapeutic agents to treat anxiety and depression.…”

Section: Introductionmentioning

confidence: 99%

Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice

et al. 2023

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The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the HTR2A receptor gene. In vitro, exposure to primary mouse cortical neurons to AAV9 vectors targeting the HT2RA gene led to a concentration-dependent decrease in spontaneous electrical activity following multielectrode array (MEA) analysis. In vivo, at 5 weeks postintranasal delivery in mice, analysis of brain samples revealed single base pair deletions and nonsense mutations, leading to an 8.46-fold reduction in mRNA expression and a corresponding 68% decrease in the 5HT-2A receptor staining. Our findings also demonstrate a significant decrease in anxiety-like behavior in treated mice. This study constitutes the first successful demonstration of a noninvasive CRISPR/Cas9 delivery platform, capable of bypassing the blood–brain barrier and enabling modulation of neuronal 5HT-2A receptor pathways. The results of this study targeting the HTR2A gene provide a foundation for the development of innovative therapeutic strategies for a broad range of neurological disorders, including anxiety, depression, attentional deficits, and cognitive dysfunction.

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“…Src/Akt cascades (Sharp and Barnes, 2020). Furthermore, adjacent membrane proteins and allosteric modulators of metabotropic 5-HT receptors have been reported to regulate the function of 5-HT receptors via altering cellular localization or molecular structure to trigger a specific downstream reaction (Sharp and Barnes, 2020;Popova et al, 2022). Another mechanism regulating the function of the 5-HT receptor is RNA editing.…”

Section: -Ht Receptor Distribution and Function Across Pain/anxiety-r...mentioning

confidence: 99%

“…In addition, the metabotropic 5-HT receptors can also recruit many other non-canonical signaling pathways, such as extracellular signal-regulated kinase (ERK) signaling pathway, phospholipase A2, and β-arrestin coupled Src/Akt cascades ( Sharp and Barnes, 2020 ). Furthermore, adjacent membrane proteins and allosteric modulators of metabotropic 5-HT receptors have been reported to regulate the function of 5-HT receptors via altering cellular localization or molecular structure to trigger a specific downstream reaction ( Sharp and Barnes, 2020 ; Popova et al, 2022 ). Another mechanism regulating the function of the 5-HT receptor is RNA editing.…”

Section: -Ht Receptor Distribution and Function Across Pain/anxiety-r...mentioning

confidence: 99%

Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety

Hao

Shi

Liu

et al. 2023

Front. Synaptic Neurosci.

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Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient’s overall quality of life. Serotonin (5-HT) in the central nervous system (CNS) has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions–especially anxiety and depression. Its widespread and diverse receptors underlie the functional complexity of 5-HT in the CNS. Recent studies found that both chronic pain and anxiety are associated with synaptic plasticity in the anterior cingulate cortex (ACC), the insular cortex (IC), and the spinal cord. 5-HT exerts multiple modulations of synaptic transmission and plasticity in the ACC and the spinal cord, including activation, inhibition, and biphasic actions. In this review, we will discuss the multiple actions of the 5-HT system in both chronic pain and injury-related anxiety, and the synaptic mechanisms behind them. It is likely that the specific 5-HT receptors would be new promising therapeutic targets for the effective treatment of chronic pain and injury-related anxiety in the future.

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The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

Cited by 36 publications

References 262 publications

Prevalence and correlates of severe anxiety in patients with first hospitalization for major depressive disorder combined with dyslipidemia: a large sample cross-sectional study

Prevalence and correlates of severe anxiety in patients with first hospitalization for major depressive disorder combined with dyslipidemia: a large sample cross-sectional study

Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice

Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety

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