Invisible wounds: Suturing the gap between the neurobiology, conventional and emerging therapies for posttraumatic stress disorder.

A sharp increase in the prevalence of neuropsychiatric disorders, including major depression, anxiety, substance use disorders and posttraumatic stress disorder (PTSD) has occurred due to the traumatic nature of the persisting COVID-19 global pandemic. PTSD is estimated to occur in up to 25% of individuals following exposure to acute or chronic trauma, and the pandemic has inflicted both forms of trauma on much of the population through both direct physiological attack as well as an inherent upheaval to our sense of safety. However, despite significant advances in our ability to define and apprehend the effects of traumatic events, the neurobiology and neuroanatomical circuitry of PTSD, one of the most severe consequences of traumatic exposure, remains poorly understood. Furthermore, the current psychotherapies or pharmacological options for treatment have limited efficacy, durability, and low adherence rates. Consequently, there is a great need to better understand the neurobiology and neuroanatomy of PTSD and develop novel therapies that extend beyond the current limited treatments. This review summarizes the neurobiological and neuroanatomical underpinnings of PTSD and discusses the conventional and emerging psychotherapies, pharmacological and combined psychopharmacological therapies, including the use of psychedelic-assisted psychotherapies and neuromodulatory interventions, for the improved treatment of PTSD and the potential for their wider applications in other neuropsychiatric disorders resulting from traumatic exposure.

"Out, out, brief candle! Life's but a walking shadow": 5-HTTLPR Is Associated With Current Suicidal Ideation but Not With Previous Suicide Attempts and Interacts With Recent Relationship Problems.

BACKGROUND: Suicide is an unresolved psychiatric and public health emergency, claiming 800,000 lives each year, however, its neurobiological etiology is still not understood. In spite of original reports concerning the involvement of 5-HTTLPR in interaction with recent stress in the appearance of suicidal ideation and attempts, replication studies have yielded contradictory results. In our study, we analyzed the association between 5-HTTLPR and lifetime suicide attempts, current suicidal ideation, hopelessness and thoughts of death as main effects, and in interaction with childhood adversities, recent stress, and different types of recent life events in a general population sample. METHODS: Two thousand and three hundred fifty-eight unrelated European volunteers were genotyped for 5-HTTLPR, provided phenotypic data on previous suicide attempts, and current suicidal ideation, hopelessness and thoughts about death, and information on childhood adversities and recent life events. Logistic and linear regression models were run with age, gender, and population as covariates to test for the effect of 5-HTTLPR as a main effect and in interaction with childhood adversities and recent life events on previous suicide attempts and current suicidal ideation. Benjamini-Hochberg FDR Q values were calculated to correct for multiple testing. RESULTS: 5-HTTLPR had no significant effect on lifetime suicide attempts either as a main effect on in interaction with childhood adversities. 5-HTTLPR had a significant main effect on current suicidal ideation in the dominant model (Q=0.0344). 5-HTTLPR did not interact with childhood adversities or total number of recent life events on any phenotypes related to current suicidal risk, however, a significant interaction effect between 5-HTTLPR and current relationship problems emerged in the case of current suicidal ideation in the dominant model (Q=0.0218) and in the case of thoughts about death and dying in the dominant (Q=0.0094) and additive models (Q=0.0281). CONCLUSION: While 5-HTTLPR did not influence previous suicide attempts or interacted with childhood adversities, it did influence current suicidal ideation with, in addition, an interaction with recent relationship problems supporting the involvement of 5-HTTLPR in suicide. Our findings that 5-HTTLPR impacts only certain types of suicide risk-related behaviors and that it interacts with only distinct types of recent stressors provides a possible explanation for previous conflicting findings.