Adolescent Suicide as a Failure of Acute Stress-Response Systems.

In the paper

“Remarkably, all of these reviews demonstrate that we know surprisingly little about the etiology of adolescent suicidal ideation and behaviors and that predictors of suicidal ideation, suicidal behavior, and death by suicide are surprisingly weak.”

What the sources say

• Supported

  The Introduction defines the review’s youth outcomes as suicidal ideation, attempts, and deaths. In “Potential etiology: Risk factors and correlates” (page unavailable), the authors say that all the correlates and risk factors reviewed have fairly modest effects; “Future directions” adds that much of the literature does not directly test etiology, leaving causal questions open. (LLM, conf=0.88)

  cites Cha et al. 2018 source
• ?Not checked — no full text of the sourcecites Franklin et al. 2017 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Glenn et al. 2017a

In the paper

“early chronic stress is linked with increased amygdala reactivity and with a lack of prefrontal regulation to acute stressors (Tottenham & Galván 2016)”

What the sources say

• Partly supported

  In the section on amygdala–PFC circuitry and developmental stress (page unavailable), the review links stress exposure to increased amygdala reactivity and reports that trauma-exposed youths failed to dampen that reactivity during an emotional-conflict task. It does not establish a general lack of prefrontal regulation in response to acute stressors: the evidence concerns emotional tasks, and it also describes increased prefrontal recruitment or adult-like regulatory connectivity in some stress-exposed youths. (LLM, conf=0.84)

  cites Tottenham & Galván 2016 sourceExperimental — accuracy not yet measured

In the paper

“Consequently, little is known regarding the processes that may immediately precede suicide, and few effective strategies designed to intervene in the hours or minutes before individuals engage in suicidal behavior are available (Asarnow et al. 2017, Cha et al. 2018, Miller et al. 2017a), perhaps particularly among youths.”

What the sources say

• Partly supported

  The Introduction says that treatments with replicated efficacy for youth suicide attempts and self-harm are lacking, supporting the claim that effective strategies are limited among youths. It does not address what is known about processes immediately preceding suicide or whether effective interventions are available in the hours or minutes before suicidal behavior; the Method describes a safety plan but does not establish its effectiveness on that timescale. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites Asarnow et al. 2017 sourceExperimental — accuracy not yet measured
• Partly supported

  The Potential etiology section says the pathways by which young people develop suicidal thoughts and act on them are not well understood, and Future directions calls for more short-term, real-time research. The Prevention section says crisis lines address immediate needs but have not been studied for reducing suicidal behaviour in youth. These passages support the broad knowledge and intervention gaps, but do not specifically establish a lack of effective interventions in the hours or minutes before suicidal behaviour across individuals generally. Page numbers are unavailable in our copy. (LLM, conf=0.82)

  cites Cha et al. 2018 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Miller et al. 2017a

In the paper

“For example, across rodent and human studies, adolescents demonstrate changes in ANS responses, including increased SNS reactivity and PNS withdrawal to acute stressors (Allen & Matthews 1997, Choi & Kellogg 1996, Kurtz & Campbell 1994, Stroud et al. 2009), suggesting that adolescents are more physiologically reactive to stressors and less able to flexibly regulate these increased signals.”

What the sources say

• ?Not checked — no full text of the sourcecites Allen & Matthews 1997 source
• Partly supported

  The Results (section 3.2) and Discussion report age-dependent responses to restraint in male rats, supporting the general point that stress responses change during adolescence. But the study measures hypothalamic norepinephrine, not SNS reactivity or PNS withdrawal, and describes this system’s stressor-responsiveness as blunted at mid-adolescence rather than increased. It does not study humans or establish less flexible regulation. (LLM, conf=0.87)

  cites Choi & Kellogg 1996 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kurtz & Campbell 1994

In the paper

“Although data from studies in developmental affective neuroscience are still emerging, accumulating evidence suggests that pubertal adaptations in acute stress-response systems likely contribute to a protracted period of increased stress reactivity and prolonged stress responses (i.e., a slower return to baseline) in adolescence, which is during the same developmental period associated with”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites Dahl & Gunnar 2009 sourceExperimental — accuracy not yet measured

In the paper

“a lower resting RSA is associated with suicidal ideation (Rottenberg et al. 2002) and distinguishes individuals with and without a history of suicide attempt (Tsypes et al. 2018)”

What the sources say

• ?Not checked — no full text of the sourcecites Rottenberg et al. 2002 source
• Partly supported

  The Results report significantly lower resting RSA in women with a history of suicide attempt than in women without one. The citing sentence attributes only this attempt-history finding to Tsypes et al.; its suicidal-ideation clause cites a different source. The Discussion cautions that the women-only finding has not been shown to generalize to men, so the unqualified reference to individuals is broader than this study supports. (LLM, conf=0.85)

  cites Tsypes et al. 2018 sourceExperimental — accuracy not yet measured

In the paper

“Early in this process, beginning before physical manifestations of puberty are evident, changes within the limbic system include synaptic pruning, increased myelinization, and a proliferation of dopamine and oxytocin receptors that facilitate more rapid and dramatic responses to social rewards and avoidance of social punishment (Casey et al. 2008, Chein et al. 2011).”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Casey et al. 2008 sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Chein et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“In sum, findings from developmental affective neuroscience suggest that adolescents experience several years during the pubertal transition with newly developed and robust responses to their social environment and a more sophisticated capacity to allow these social experiences to shape their self-concept, but without mature abilities to regulate their emotions or inhibit impulsive responses (Casey”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Casey et al. 2008 sourceExperimental — accuracy not yet measured

In the paper

“Even the effects of prior suicidal ideation and behaviors are relatively weak in predicting future suicidal behavior (Ribeiro et al. 2016), reflecting that in most studies, only a minority of those who attempt suicide are likely do so again.”

What the sources say

• Supported

  The citation is attached to the claim that prior suicidal ideation and behaviors are relatively weak predictors, not to the citing authors’ subsequent explanation about repeat attempts. The Discussion (page unavailable) states that prior self-injurious thoughts and behaviors confer risk, but their effects are substantially weaker than anticipated and may not improve prediction much beyond chance. (LLM, conf=0.92)

  cites Ribeiro et al. 2016 source

In the paper

“Less is known regarding adolescent-specific changes in peripheral stress-response systems, although research has begun examining typical adolescent levels of immune system markers, such as cytokines (Riis et al. 2014).”

What the sources say

• Supported

  The Introduction says knowledge of salivary cytokine levels in youth is shallow and that the study addresses this gap. The Methods (Participants and Analytic Strategy) describe measuring cytokine levels and examining their associations with age and pubertal stage in adolescent girls. This supports the sentence’s qualified claim that research has begun examining these markers in adolescents. (LLM, conf=0.91)

  cites Riis et al. 2014 source

In the paper

“Research confirms that adolescents experience increased physiological responses to stressors (Stroud et al. 2009), increased prefrontal brain activation during social evaluation (Somerville 2013), and increased difficulty implementing cognitive control skills in the context of emotionally evocative events (Cohen et al. 2016, Somerville et al. 2011).”

What the sources say

• Supported

  Stroud et al. is cited only for increased physiological responses to stressors, not for the claims about brain activation or cognitive control. The Abstract reports significantly greater cortisol, salivary alpha-amylase, and blood-pressure stress responses in adolescents than in children. (LLM, conf=0.94)

  cites Stroud et al. 2009 source
• Supported

  In “Vigilance to social evaluation,” the paper reports that medial prefrontal cortex activity during peer video monitoring increased markedly in adolescence and partially subsided in adulthood. This supports the part of the citing sentence attributed to Somerville (2013); the other claims have separate citations. (LLM, conf=0.93)

  cites Somerville 2013 source
• ?Not checked — no full text of the sourcecites Cohen et al. 2016 source

In the paper

“Initial findings revealed a significant effect for cortisol hyperreactivity (and a marginal trend for hyporeactivity) to the TSST on the risk for suicidal ideation 3 months later, even after controlling for the lifetime history of suicidal ideation and other distal risk factors (e.g., impulsivity) (Giletta et al. 2015)”

What the sources say

• Supported

  The Results (Multivariate Predictors of Adolescent Suicidal Ideation; page not available) report that hyperresponsive adolescents were about 16 times more likely than the normative group to report suicidal ideation at three months, with a marginal trend for the hyporesponsive group (p=0.087). The Methods (Strategy of Analyses; page not available) describe models including impulsiveness and other baseline predictors, and the Results state that the follow-up association remained after controlling for lifetime suicidal ideation. (LLM, conf=0.93)

  cites Giletta et al. 2015 source

In the paper

“compared with nonsuicidal controls, youths with a history of suicidal behavior had decreased gray matter volumes in the hippocampus and cerebellum and decreased functional connectivity between the amygdala and the left ventral and right rostral PFC when viewing emotional faces (Johnston et al. 2017)”

What the sources say

• Supported

  The Abstract Results and Discussion report lower hippocampal and cerebellar gray matter volumes and lower amygdala connectivity to left ventral and right rostral prefrontal regions in suicide attempters than non-attempters. The Method identifies both groups as adolescents or young adults with bipolar disorder; the Results specify that connectivity differences occurred during emotional-face conditions. Here, “nonsuicidal controls” refers to the study’s non-attempter comparison group, not a healthy control group. (LLM, conf=0.91)

  cites Johnston et al. 2017 source

In the paper

“DNA methylation systematically alters gene expression, resulting in an increased risk for psychopathology and, specifically, suicide (Haghighi et al. 2014)”

What the sources say

• Partly supported

  The Introduction links methylation at specific sites to decreased gene expression, and the Abstract says increased methylation may contribute to psychopathology and suicide risk. But the Discussion explicitly says the study cannot establish a causal relationship between increased DNA methylation and suicide risk, so the citing sentence overstates the evidence by saying methylation results in increased risk. (LLM, conf=0.88)

  cites Haghighi et al. 2014 sourceExperimental — accuracy not yet measured

In the paper

“We have replicated a similar pattern of results in a separate sample of adolescents and in a sample of emerging adults (Miller et al. 2018).”

What the sources say

• Partly supported

  The Methods (Participants; page unavailable) describe one sample of 49 adolescents, and the Discussion reports differences in neural activation associated with suicidal ideation in that sample. This supports the reference to a similar pattern in adolescents, but the paper does not report a separate sample of emerging adults. (LLM, conf=0.86)

  cites Miller et al. 2018 sourceExperimental — accuracy not yet measured

In the paper

“Adolescents who engage in NSSI or make suicide attempts are significantly more likely to engage in future suicidal behavior (Ribeiro et al. 2016), especially within the first few months following an attempt (Goldston et al. 2001)”

What the sources say

• Supported

  The Results (Risk factor category analyses) report significantly increased odds of future suicide attempts after NSSI (OR 4.27) or a prior suicide attempt (OR 3.61). The Results (Moderator analyses, Sample age) also report a significant association with future attempts in adolescent samples. The first-few-months qualifier is cited to Goldston et al. (2001), not Ribeiro et al., and is outside this verdict. (LLM, conf=0.88)

  cites Ribeiro et al. 2016 source
• ?Not checked — no full text of the sourcecites Goldston et al. 2001 source

In the paper

“adverse social experiences characterized by loss or threat activate proinflammatory cytokine activity (Giletta et al. 2018, Slavich & Cole 2013) and trigger alterations in the genes regulating proinflammatory cytokine production (Slavich et al. 2010)”

What the sources say

• Partly supported

  The Peer Victimization and Adolescent Inflammatory Responses to Social Stress section (page unavailable) says threats to the social self may increase acute inflammatory responses. The Results (page unavailable) find greater IL-6 and IL-1β reactivity among girls with more peer victimization, but no significant average cytokine increase after the stressor. Thus, the citation supports a narrower, qualified link than the claim’s general statement that loss- or threat-related experiences activate cytokine activity. The separate claim about gene alterations is attributed to Slavich et al. (2010), not this source. (LLM, conf=0.84)

  cites Giletta et al. 2018 sourceExperimental — accuracy not yet measured
• Supported

  The citation to Slavich and Cole is attached to the first clause, about adverse social experiences activating proinflammatory activity; the later claim about alterations in genes is cited to a different source. In “Social Signal Transduction” (page unavailable), the paper says that even the threat of a significant social loss can activate the inflammatory transcriptional response, and that psychosocial stress or threat can lead to increased inflammatory activity. “Socially Sensitive Genes” identifies proinflammatory cytokine genes as part of the immune response under discussion. (LLM, conf=0.88)

  cites Slavich & Cole 2013 source
• Supported

  Section 3.2, “Social rejection and inflammation” (page not provided), reports that social isolation and interpersonal stress upregulate expression of genes that promote inflammation. This supports the gene-regulation clause attributed to Slavich et al.; the paper describes altered gene expression, not changes to DNA sequence. (LLM, conf=0.86)

  cites Slavich et al. 2010 source

In the paper

“An emerging line of research points to altered neural activation (Just et al. 2017, Miller et al. 2018, Pan et al. 2013, Quevedo et al. 2016) and neural network connectivity (Chase et al. 2017; Ordaz et al. 2018; Zhang et al. 2014, 2016) in PFC regions among individuals with a history of suicidal ideation or behavior.”

What the sources say

• Supported

  The Results section reports negligible stable activation in anterior frontal regions among suicidal ideators, compared with controls. Just et al. is cited for altered neural activation; the sentence attributes neural network connectivity to other studies. (LLM, conf=0.92)

  cites Just et al. 2017 source
• Supported

  The Miller et al. citation is attached to the neural-activation portion of the sentence, not the connectivity portion. The Discussion reports different activation in frontal control regions between adolescents with and without histories of suicidal ideation during an emotion-regulation task. (LLM, conf=0.93)

  cites Miller et al. 2018 source
• Supported

  Pan et al. is cited for the neural-activation portion of the sentence, not the connectivity portion. The Discussion reports greater left dorsolateral prefrontal activity in adolescents with a history of depression and suicide attempt than in depressed adolescents without an attempt when viewing 50% intensity angry faces. Our copy does not provide a page number for this passage. (LLM, conf=0.93)

  cites Pan et al. 2013 source

In the paper

“Following acute stress, proinflammatory cytokines signal the brain to engage in sickness behaviors closely mimicking depression and, in some cases, leading to clinical depression among physically ill people (Dantzer et al. 2008)”

What the sources say

• Partly supported

  The Abstract says that pro-inflammatory cytokines act on the brain to cause sickness behaviour, that its symptoms resemble depression, and that sustained immune activation may contribute to depression in vulnerable physically ill people. It describes infection and ongoing inflammation, however, not acute stress as the trigger; it also says the similarity between sickness and depression is only partial. No page number is provided in our copy. (LLM, conf=0.88)

  cites Dantzer et al. 2008 sourceExperimental — accuracy not yet measured

In the paper

“those who become suicidal might be predicted by understanding whether adolescents have recently been exposed to and, perhaps, consequently possess less-aversive attitudes toward suicide (Nock et al. 2010)”

What the sources say

• Partly supported

  The Results (page not provided) show that an implicit association between death/suicide and self predicted subsequent suicide attempts in psychiatric emergency-department patients. The paper does not establish that these patients had less-aversive attitudes toward suicide, or assess recent exposure to suicide as a predictor. It does not establish the proposed prediction specifically for adolescents. (LLM, conf=0.86)

  cites Nock et al. 2010 sourceExperimental — accuracy not yet measured

In the paper

“higher-than-usual peer stress predicted suicidal ideation over 18 months, regardless of HPA axis function, but it predicted suicidal behavior only among girls with blunted cortisol responses to the TSST at baseline (Eisenlohr-Moul et al. 2018a)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Eisenlohr-Moul et al. 2018a

In the paper

“Yet prior work has not elucidated the biological or psychological processes that immediately follow stressful experiences and occur within the hours, minutes, or seconds prior to suicidal behavior.”

In the paper

“We suggest that a promising area for future research is to examine adolescent suicide as a failure of biological responses to acute stress in the proximal moments of a suicidal crisis.”

• Also stated in: § INTRODUCTION · hedged

  “Specifically, we suggest that failures in biological responses to acute stress may underlie acute suicidal crises in youth.”

• Also stated in: § Organization of Review · hedged

  “We suggest that adolescent suicidal crises may result from failures of biological responses to acute stress.”

In the paper

“Further, it is not clear how these factors confer risk in the proximal moments of a suicidal crisis.”

In the paper

“Biologically equipped with an increased investment in social interactions and enhanced social sensitivity, adolescents enter a world involving novel, complex, and unfamiliar social interactions with increased stakes for success, but with immature biological resources to adequately regulate social stress.”

In the paper

“While these risk factors provide information about global risk for any suicidal ideation or behaviors in the future, they are nonspecific. In other words, they do not provide information about which youths are more vulnerable to these risk factors or when a given youth will experience suicidal ideation or engage in suicidal behavior.”

In the paper

“For example, they note that while internalizing risk factors accounted for nearly 66% of all predictors examined in the literature, they were not strongly related to future risk for suicidal ideation or behaviors when omnibus effect sizes are considered in meta-analyses (odds ratios between 1.17 and 1.71; Franklin et al. 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Franklin et al. 2017 source

In the paper

“As compared with children and adults, adolescents report higher levels of peer-related interpersonal stressors and greater emotional reactivity to these types of stressors (Rudolph 2014).”

What the sources say

• ?Not checked — no full text of the sourcecites Rudolph 2014 source

In the paper

“Markers of central stress-response systems may be promising predictors of proximal suicide risk in adolescents.”

In the paper

“Indeed, research suggests that the pubertal transition is associated with marked increases in adolescents’ interactions with peers, concomitant decreases in parental supervision, and more severe parent–child conflict (Prinstein & Giletta 2016).”

What the sources say

• ?Not checked — no full text of the sourcecites Prinstein & Giletta 2016 source

In the paper

“Adolescence is marked by dramatic changes in biological and social systems that simultaneously increase acute stress-response system reactivity and adolescents’ orientation toward social stimuli, thus creating a uniquely vulnerable time frame for the emergence of suicidal ideation and behavior.”

In the paper

“For healthy individuals, stress thresholds may be quite high.”

In the paper

“there are several factors that may increase the likelihood that adolescents will readily consider suicide, including (a) their own prior experiences with self-injury and suicide, such as prior NSSI, ideation, or attempts; (b) their knowledge of others’ (a relative’s or celebrity’s) suicidal behavior; and (c) peer socialization toward self-injurious thoughts and behaviors”

In the paper

“suicide is most likely to occur when at least one of two conditions is met”

In the paper

“a fact that, unfortunately, has been unaddressed in almost all prior theories regarding suicide”

In the paper

“Markers of several peripheral response systems also may be relevant correlates of adolescent suicide.”

In the paper

“both higher and lower levels of cortisol have been associated with suicide”

In the paper

“is associated with relevant suicidal outcomes, at least preliminarily, based on limited empirical studies”

In the paper

“many other domains of psychopathology also may be predicted by these same distal factors, the onset of social–biological adaptations to puberty, and atypical stress-response systems”

In the paper

“resting RSA and greater RSA withdrawal to a noninterpersonal frustration task did not predict engagement in self-injurious thoughts and behavior (defined as a composite of NSSI, suicidal ideation, and suicidal behavior) during the following 6 months”

What the sources say

• ?Not checked — no full text of the sourcecites Wielgus et al. 2016 source

In the paper

“Thus, suicide propinquity may moderate the association between adolescents’ acute stress response and suicidal ideation or behavior.”