Latest updates on the serotonergic system in depression and anxiety

Abstract

Psychiatric disorders are among the leading causes of global health burden, with depression and anxiety being the most disabling subtypes. The two common disorders, depression and anxiety, usually coexist and are pathologically polygenic with complicated etiologies. Current drug-based therapies include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and 5-hydroxytryptamine partial agonists. However, these modalities share common limitations, such as slow onset and low efficacy, which is why potential mechanistic insights for new drug targets are needed. In this review, we summarize recent advances in brain localization, pathology, and therapeutic mechanisms of the serotonergic system in depression and anxiety.

Atractylenolide I improves behaviors in mice with depression‐like phenotype by modulating neurotransmitter balance via 5‐HT2A

“…This view has also been confirmed by the autopsy results of patients dying of depression-induced suicide. The enhanced binding ability of 5-HT1A autoreceptors leads to reduced 5-HT neuroconduction, while the compromised binding ability of postsynaptic 5-HT1A receptors weakens the 5-HT-mediated behavioral response (Lin et al, 2023). Hence, the occurrence of depression is closely associated with the co-action of 5-HT1A receptors in the pre-and postsynaptic membranes (Deng et al, 2023).…”

Anxiety in oncology outpatients is associated with perturbations in pathways identified in anxiety focused network pharmacology research

“…This study evaluated for perturbed signaling pathways associated with low versus high levels of state anxiety in oncology patients. Given that the underlying mechanisms for anxiety may relate to how various anxiolytic drugs exert their effect(s) [ 70 ], our pathways were compared to a list of pathways identified in network pharmacology studies [ 15 – 22 ]. Taken together, these findings increase our knowledge of the molecular mechanisms that underlie anxiety in patients receiving chemotherapy.…”

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review

“…Serotonergic neurons are mainly distributed in brainstem raphe nuclei, from which projections are sent to wide areas of the brain ( Paquelet et al, 2022 ; Figure 2 ). A battery of canonical signaling pathways is involved in the 5-HT-mediated system, including the phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K-Akt/mTOR) signaling pathway, extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway ( Albert and Vahid-Ansari, 2019 ), and cAMP response element-binding protein/cAMP response element-binding protein (PKA/CREB) pathway ( Yue et al, 2022 ; Lin et al, 2023 ).…”