The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference
2022
Nina K. Popova | Anton S. Tsybko | Vladimir S. Naumenko
Being different multifactorial forms of psychopathology, aggression, depression and suicidal behavior, which is considered to be violent aggression directed against the self, have principal neurobiological links: preclinical and clinical evidence associates depression, aggression and suicidal behavior with dysregulation in central serotonergic (5-HT) neurotransmission. The implication of different types of 5-HT receptors in the genetic and epigenetic mechanisms of aggression, depression and suicidality has been well recognized. In this review, we consider and compare the orchestra of 5-HT receptors involved in these severe psychopathologies. Specifically, it concentrates on the role of 5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, 5-HT<sub>2C</sub>, 5-HT<sub>3</sub> and 5-HT<sub>7</sub> receptors in the mechanisms underlying the predisposition to aggression, depression and suicidal behavior. The review provides converging lines of evidence that: (1) depression-related 5-HT receptors include those receptors with pro-depressive properties (5-HT<sub>2A</sub>, 5-HT<sub>3</sub> and 5-HT<sub>7</sub>) as well as those providing an antidepressant effect (5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>2C</sub> subtypes). (2) Aggression-related 5-HT receptors are identical to depression-related 5-HT receptors with the exception of 5-HT<sub>7</sub> receptors. Activation of 5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2C</sub> receptors attenuate aggressiveness, whereas agonists of 5-HT<sub>3</sub> intensify aggressive behavior.
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