Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complem...Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.展开更多
Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous sys...Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous system is susceptible to shifts in activity of epigenetic modifiers,these allow for significant plasticity and response to rapid changes in the environment.Among the most studied epigenetic modifications in depressive disorder is DNA methylation,with findings centered on the brain-derived neurotrophic factor gene,the glucocorticoid receptor gene,and the serotonin transporter gene.In order to identify biomarkers that would be useful in clinical settings,for diagnosis and for treatment response,further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed.Studies on cornerstone antidepressants,such as selective serotonin reuptake inhibitors,selective serotonin and norepinephrine reuptake inhibitors,norepinephrine,and dopamine reuptake inhibitors and their effects on depressive disorder are available,but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies.In addition,two novel drugs,ketamine and esketamine,are being investigated particularly in association with treatment of resistant depression,which is one of the hot topics of contemporary research and the field of precision psychiatry.展开更多
基金Supported by Slovenian Research and Innovation Agency Program,No.P1-0390 and No.N3-0349Slovenian Research and Innovation Agency Program,Young Researcher Grant(toŠmon J).
文摘Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.
基金Supported by Slovenina Reserach Agency,Young Researcher Grant to I?,No.P1-0390。
文摘Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous system is susceptible to shifts in activity of epigenetic modifiers,these allow for significant plasticity and response to rapid changes in the environment.Among the most studied epigenetic modifications in depressive disorder is DNA methylation,with findings centered on the brain-derived neurotrophic factor gene,the glucocorticoid receptor gene,and the serotonin transporter gene.In order to identify biomarkers that would be useful in clinical settings,for diagnosis and for treatment response,further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed.Studies on cornerstone antidepressants,such as selective serotonin reuptake inhibitors,selective serotonin and norepinephrine reuptake inhibitors,norepinephrine,and dopamine reuptake inhibitors and their effects on depressive disorder are available,but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies.In addition,two novel drugs,ketamine and esketamine,are being investigated particularly in association with treatment of resistant depression,which is one of the hot topics of contemporary research and the field of precision psychiatry.
