The complement cascade not only is an innate immune response that enables removal of pathogens but also plays an important role in microglia-mediated synaptic refinement during brain development. Complement C3 is elevated in Alzheimer's disease (AD), colocalizing with neuritic plaques, and appears to contribute to clearance of Aβ by microglia in the brain. Previously, we reported that C3-deficient C57BL/6 mice were protected against age-related and region-specific loss of hippocampal synapses and cognitive decline during normal aging. Furthermore, blocking complement and downstream iC3b/CR3 signaling rescued synapses from Aβ-induced loss in young AD mice before amyloid plaques had accumulated. We assessed the effects of C3 deficiency in aged, plaque-rich APPswe/PS1dE9 transgenic mice (APP/PS1; KO). We examined the effects of C3 deficiency on cognition, Aβ plaque deposition, and plaque-related neuropathology at later AD stages in these mice. We found that 16-month-old APP/PS1; KO mice performed better on a learning and memory task than did APP/PS1 mice, despite having more cerebral Aβ plaques. Aged APP/PS1; KO mice also had fewer microglia and astrocytes localized within the center of hippocampal Aβ plaques compared to APP/PS1 mice. Several proinflammatory cytokines in the brain were reduced in APP/PS1; KO mice, consistent with an altered microglial phenotype. C3 deficiency also protected APP/PS1 mice against age-dependent loss of synapses and neurons. Our study suggests that complement C3 or downstream complement activation fragments may play an important role in Aβ plaque pathology, glial responses to plaques, and neuronal dysfunction in the brains of APP/PS1 mice.

Objective: As part of the National Suicide Prevention Lifeline's crisis response system, the Lifeline Crisis Chat Network (LCC) answers chats from hundreds of thousands of at-risk individuals yearly. The study's objective was to assess the effectiveness of these online crisis interventions.Method: Data from 39,911 pre-chat surveys and 13,130 linked pre-and post-chat surveys completed by LCC chatters from October 2017-June 2018 were analyzed.The relationship of several effectiveness measures with chatter demographics, pre-chat distress, suicidal ideation, and chatters' perceptions of engagement with their counselors was examined using a series of logistic regression analyses.Results: Chatters were significantly and substantially less distressed at the end of the chat intervention than at the beginning. By the end of the chat, two-thirds of suicidal chatters reported that the chat had been helpful, while just under half reported being less suicidal. Conclusions:Our study offers empirical evidence for the Lifeline's online crisis chat services' effectiveness, but also highlights areas for improvement. This is of critical import in light of the recent designation of 988 as the nationwide number for the Lifeline beginning in 2022, which will increase the Lifeline's prominence in providing suicide prevention and mental health crisis interventions in the United States.

Objective: Specific content characteristics of suicide media reporting might differentially impact suicides in the population, but studies have not considered the overarching theme of the respective media stories and other relevant outcomes besides suicide, such as help-seeking behaviours. Methods: We obtained 5652 media reports related to suicide from 6 print, 44 broadcast and 251 online sources in Oregon and Washington states, published between April 2019 and March 2020. We conducted a content analysis of stories regarding their overarching focus and specific content characteristics based on media recommendations for suicide reporting. We applied logistic regression analyses to assess how focus and content characteristics were associated with subsequent calls to the US National Suicide Prevention Lifeline (Lifeline) and suicides in these two states in the week after publication compared to a control time period. Results: Compared to a focus on suicide death, a focus on suicidal ideation, suicide prevention, healing stories, community suicide crises/suicide clusters and homicide suicide was associated with more calls. As compared to a focus on suicide death, stories on suicide prevention and stories on community suicide crises/suicide clusters were also associated with no increase in suicides. Regarding specific content characteristics, there were associations that were largely consistent with previous work in the area, for example, an association of celebrity suicide reporting with increases in suicide. Conclusion: The overall focus of a media story may influence help-seeking and suicides, and several story characteristics appear to be related to both outcomes. More research is needed to investigate possible causal effects and pathways.

Adolescents’ exposure to a peer’s suicide has been found to be associated with, as well as to predict, suicidal ideation and behavior. Although postvention efforts tend to be school-based, little is known about the impact of a schoolmate’s suicide on the school’s student population overall. The present study seeks to determine whether there is excess psychological morbidity among students in a school where a schoolmate has died by suicide, and whether students’ attitudes about coping and help-seeking strategies are more or less problematic in such schools. Students in twelve high schools in Suffolk and Westchester counties in New York State—2865 students at six schools where a student had died by suicide within the past six months, and 2419 students at six schools where no suicide had occurred within the current students’ tenure—completed an assessment of their suicidal ideation and behavior, depressive symptoms, coping and help-seeking attitudes, stressful life events, and friendship with suicide decedent (if applicable). No excess morbidity (i.e., serious suicidal ideation/behavior and depression) was evident among the general student population after a schoolmate’s death by suicide; however, the risk of serious suicidal ideation/behavior was elevated among students at exposed schools who had concomitant negative life events. There was a significant relationship between friendship with the decedent and morbidity, in that students who were friends, but not close friends, of the decedents had the greatest odds of serious suicidal ideation/behavior. Overall, students in exposed schools had more adaptive attitudes toward help-seeking; but this was not true of the decedents’ friends or students with concomitant negative life events. The implications of the findings for postvention strategies are discussed.

Abstract. Background: Research indicates that the COVID-19 pandemic caused increases in psychological distress and suicidal ideation. Aims: To describe the ways suicidal callers to the National Suicide Prevention Lifeline (Lifeline) perceived COVID-19 to have impacted them and assess whether these callers perceived COVID-19-related stress as contributing to their suicidal thoughts. Method: Telephone interviews were conducted with 412 suicidal callers to 12 Lifeline centers. Logistic regression analyses were used to examine the associations between demographic factors and individual COVID-19 stressors and to determine whether callers who endorsed COVID-19-related stress as contributing to their suicidal thoughts differed from those who did not regarding demographics, current suicide risk, history of suicidality, Lifeline use, or individual COVID-19 stressors. Results: Over half of callers reported that COVID-19-related stress contributed to their suicidal ideation (CRSSI). Callers who endorsed CRSSI had higher odds than those who did not of mentioning financial difficulties when asked how COVID-19 impacted them. The two groups of callers did not differ on the other factors examined. Limitations: Interviewed callers may not be representative of all Lifeline callers. Conclusion: Despite the subjective burden of COVID-19-related stress on suicidal Lifeline callers, this was not associated with new suicidality or heightened suicide risk.