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

“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).”

“Consistent with allostatic load theories (McEwen 2007) regarding moderate levels of cortisol facilitating flexible, adaptive responses to environmental stressors, findings suggest that both hyper- and hypocortisol responses reflect disruptions in the HPA axis system that may increase the…”

“More recent theories also have emphasized negative interpersonal states that give rise to suicidal thinking (Joiner 2005, Klonsky & May 2015, O’Connor 2011, Van Orden et al. 2010), including thwarted belongingness or perceived burdensomeness.”

“Recently, several theoretical (Glenn et al. 2017a), systematic (Cha et al. 2018), and meta-analytic reviews (Franklin et al. 2017, Glenn et al. 2018, Ribeiro et al. 2016) have been published on the topic of suicide, with one review by Cha and colleagues (2018) focusing specifically on youths.”

“In this way, the PNS acts as a brake on the SNS by reducing the heart rate and facilitating alert engagement in the environment (Porges 2003, 2007).”

“…the activity of intracellular, proinflammatory immune response genes [e.g., tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL1B)] that release protein molecules called cytokines, which are the primary mediators of systemic inflammation (Raison et al. 2006, Slavich et al. 2014).”

“…of novel risk factors or developmental transactions between intra- and interpersonal risk factors unique to the adolescent period that elucidate why suicidal ideation and behaviors are more likely to appear within this period than any other period in the life span (Nock et al. 2008, 2013).”

“Adolescence also is marked by an increase in the frequency and emotional intimacy of dyadic peer experiences, with both best friendships and emerging romantic relationships occupying more of adolescents’ attention and interest (Rose & Rudolph 2006, Steinberg & Morris 2001).”

“…to acute stress that may help explain the proximal processes occurring in the moments between adolescents’ exposure to stress and their experience of suicidal ideation and behavior (see also Cha et al. 2018; Chang et al. 2016; Lutz et al. 2017; Pan et al. 2011, 2016; Turecki & Brent 2016).”

“Notably, the distinction between these constructs is sometimes unclear, particularly among youths who may not be able to articulate their intent to die before considering or engaging in suicidal behavior (Hawton et al. 2012, Prinstein 2008).”

“…that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015, Nederhof et al. 2015, Slavich & Irwin 2014).”

“Linehan (1993) highlighted the role of emotional dysregulation preceding suicide, and both Baumeister (1990) and Beck (1987) posited that increasingly distorted thinking leads an individual to view destructive behaviors as a reasonable option for dealing with intolerable distress.”

“Altered frontolimbic connectivity could help explain why some youths who experience an acute stressor are unable to leverage higher-order skills, such as cognitive reappraisal (Buhle et al. 2014), to modulate subcortical activation and, subsequently, begin experiencing suicidal ideation.”

“More recent theories also have emphasized negative interpersonal states that give rise to suicidal thinking (Joiner 2005, Klonsky & May 2015, O’Connor 2011, Van Orden et al. 2010), including thwarted belongingness or perceived burdensomeness.”

“Research also indicates that exposure to chronic stress during early development has lasting effects on stress responses (see McEwen & Gianaros 2010 for a review).”

“ADOLESCENCE: A CRITICAL TIME OF VULNERABILITY TO SUICIDE As reviewed above, few developmentally based theories have been offered to help explain why suicidal ideation and behaviors increase in prevalence at the adolescent transition (Nock et al. 2013).”

“Operating in a negative feedback loop, glucocorticoids signal the HPA axis to shut off following the end of a stressor via targeted brain structures, including the PVN, hippocampus, amygdala, and PFC regions (Herman et al. 2003, Tasker & Herman 2011).”

“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.”

“The vagus nerve modulates the faster-acting SNS and transmits afferent signals to subcortical structures of the brain, including the amygdala, via the nucleus tractus solitarius (Berthoud & Neuhuber 2000).”

“…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).”

“Peripheral inflammation is similarly controlled via subcortical neural structures, including the hypothalamus (Sternberg 2006).”

“…stimuli during adolescence relative to reactivity in children and adults (Silvers et al. 2012) and increased social sensitivity among adolescents, as reflected by activity in the anterior cingulate cortex, compared with sensitivity in children and adults (Somerville 2013, Somerville et al. 2013).”

“…thoughts; stress response; suicidal behavior; acute suicidal crisis; proximal risk factors INTRODUCTION Suicide is the second leading cause of death worldwide among individuals between 10 and 24 years of age (Curtin et al. 2016, Mokdad et al. 2016), representing an alarming public health crisis.”

“Adolescents’ bids to enhance or maintain this form of peer status frequently involve the use of overt or relational aggression strategies that often are cited as powerful predictors of adolescent suicide (Juvonen & Graham 2014, Massing-Schaffer et al. 2018).”

“…data suggest that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015, Nederhof et al. 2015,…”

“A growing body of data also suggests that adolescents may be particularly susceptible toward the socialization of self-injury when a close friend endorses depressive symptoms, NSSI, or suicidal ideation and behavior (Bearman & Moody 2004, Kandel et al. 1991, Rew et al. 2001, Yoder 1999).”

“In recent years, adolescence has also been associated with an increase in online interactions with peers, offering remarkably frequent opportunities for new forms of interpersonal relationships and social expectations (Nesi et al. 2018).”

“At the peer group level, adolescence is marked by the introduction of a new form of peer status, reflecting adolescents’ dominance, power, influence, and visibility (Cillessen & Rose 2005, Parkhurst & Hopmeyer 1998).”

“The onset of puberty, characterized by rapid external physical and internal biological changes, includes extensive neural network changes in the brain and alterations in hormonal systems as adolescents move toward sexual maturity (Gunnar et al. 2009, Rudolph 2014, Susman & Dorn 2009).”

“…A uthor M anuscript risk factors may experience psychological symptoms following stress, 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).”

“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…”

“Recently, several theoretical (Glenn et al. 2017a), systematic (Cha et al. 2018), and meta-analytic reviews (Franklin et al. 2017, Glenn et al. 2018, Ribeiro et al. 2016) have been published on the topic of suicide, with one review by Cha and colleagues (2018) focusing specifically on youths.”

“…as well as suicidal ideation, suicidal plans, suicidal gestures, and a range of suicidal behaviors (i.e., interrupted attempts; aborted attempts; suicidal attempts, ranging from minor to those that require medical attention; and death by suicide) (O’Carroll et al. 1996, Silverman et al. 2007).”

“At the peer group level, adolescence is marked by the introduction of a new form of peer status, reflecting adolescents’ dominance, power, influence, and visibility (Cillessen & Rose 2005, Parkhurst & Hopmeyer 1998).”

“Adolescent suicide also must be considered in the context of cultural factors, such as race, ethnicity, and religiosity, that are remarkably relevant but often neglected determinants of suicidal outcomes (Goldston et al. 2008).”

“Nevertheless, prior research clearly has revealed NSSI as both a correlate and risk factor for suicidal ideation and behavior; yet the predictors and developmental course of NSSI differ from that of suicidal ideation and behaviors (see reviews by Fox et al. 2015 and Liu et al. 2017).”

“Only three randomized controlled trials have demonstrated efficacy in temporarily reducing the risk for suicidal behavior among adolescents with a history of suicide attempts or self-harm (Asarnow et al. 2017, Esposito-Smythers et al. 2011, McCauley et al. 2018).”

“This system is modulated by the parasympathetic branch (parasympathetic nervous system; PNS) of the ANS, which has been specifically implicated in self-regulatory processes (Beauchaine 2015).”

“Findings indicate that adults with a history of suicidal behavior show increased levels of interleukin6 (IL-6) (Janelidze et al. 2011, Lindqvist et al. 2009, Serafini et al. 2013), increased tumor necrosis factor-α (TNF-α) (Janelidze et al. 2011), decreased levels of IL-2 (Janelidze et al. 2011,…”

“…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).”

“…has demonstrated that 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), increased…”

“…neuroimaging research demonstrates increased neural reactivity to negative stimuli during adolescence relative to reactivity in children and adults (Silvers et al. 2012) and increased social sensitivity among adolescents, as reflected by activity in the anterior cingulate cortex, compared with…”

“Last, most suicidal behavior among youths occurs in response to a discrete stressful precipitant (King & Merchant 2008).”

“…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 greater exposure to interpersonal stress (Dahl & Gunnar 2009).”

“Although still an emerging area of research, cellular-level responses to acute stress, such as free circulating mitochondrial DNA (mtDNA), result in downstream systemic inflammation (Picard et al. 2014).”

“…stimuli during adolescence relative to reactivity in children and adults (Silvers et al. 2012) and increased social sensitivity among adolescents, as reflected by activity in the anterior cingulate cortex, compared with sensitivity in children and adults (Somerville 2013, Somerville et al. 2013).”

“…that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015, Nederhof et al. 2015, Slavich & Irwin 2014).”

“…behavior also have been well documented through research on suicide clusters (see Brent et al. 1989, Gould 1990, Gould et al. 1990, Joiner 1999, Phillips & Carstensen 1986), yielding best practice recommendations for the media and school personnel when covering the death by suicide of a…”

“In other words, the PFC can assist in managing subcortical activation resulting from exposure to a stressor to achieve an efficient and effective acute stress response.”

“This hypothesis has some support from emerging studies demonstrating that compared with controls, individuals with suicidal ideation and behavior have increased proinflammatory cytokine activity (Black & Miller 2015).”

“…cytokine activity (Giletta et al. 2018, Slavich & Cole 2013) and trigger alterations in the genes regulating proinflammatory cytokine production (Slavich et al. 2010), increased inflammatory brain signaling in the context of exposure to social stressors may distinguish adolescents at risk for…”

“…2013), increased tumor necrosis factor-α (TNF-α) (Janelidze et al. 2011), decreased levels of IL-2 (Janelidze et al. 2011, Serafini et al. 2013), and increased levels of cytokine-stimulated plasma kynurenine (Sublette et al. 2011) and quinolinic acid (Erhardt et al. 2013) in cerebrospinal fluid.”

“…models also have demonstrated that chronic exposure to stress, particularly during early childhood and adolescent development, is associated with structural and functional changes in both the amygdala and hippocampus, thus increasing the risk for altered acute stress responses (Radley et al. 2015).”

“A growing body of data also suggests that adolescents may be particularly susceptible toward the socialization of self-injury when a close friend endorses depressive symptoms, NSSI, or suicidal ideation and behavior (Bearman & Moody 2004, Kandel et al. 1991, Rew et al. 2001, Yoder 1999).”

“Findings from rodent studies and human neuroimaging research have revealed that early chronic stress is linked with increased amygdala reactivity and with a lack of prefrontal regulation to acute stressors (Tottenham & Galván 2016).”

“In a sample of adolescents and emerging adults (age range 15–30 years), individuals with a history of suicide attempt had higher levels of TNF-α and C-reactive protein compared with those with a history of suicidal ideation and with healthy controls (Melhem et al. 2017).”

“Polyamine levels increase following exposure to stress, and the magnitude of this response is associated with the intensity of the stressor and the behavioral response to the stressor (Gilad & Gilad 2003, Turecki 2014).”

“Operating in a negative feedback loop, glucocorticoids signal the HPA axis to shut off following the end of a stressor via targeted brain structures, including the PVN, hippocampus, amygdala, and PFC regions (Herman et al. 2003, Tasker & Herman 2011).”

“Glucocorticoids (cortisol in humans) are the end point of the HPA axis system and are responsible for many of the adaptive acute stress responses, such as enhanced memory (Barsegyan et al. 2010) and regulation of inflammatory immune signaling (Slavich & Irwin 2014).”

“Only three randomized controlled trials have demonstrated efficacy in temporarily reducing the risk for suicidal behavior among adolescents with a history of suicide attempts or self-harm (Asarnow et al. 2017, Esposito-Smythers et al. 2011, McCauley et al. 2018).”

“…2013), increased tumor necrosis factor-α (TNF-α) (Janelidze et al. 2011), decreased levels of IL-2 (Janelidze et al. 2011, Serafini et al. 2013), and increased levels of cytokine-stimulated plasma kynurenine (Sublette et al. 2011) and quinolinic acid (Erhardt et al. 2013) in cerebrospinal fluid.”

“…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), suggesting altered signaling between subcortical and PFC control regions.”

“…through affiliations with other distressed teens, some emerging longitudinal evidence suggests that a friend’s suicide is a meaningful predictor of an adolescent’s own risk for future NSSI (Giletta et al. 2013, Prinstein et al. 2010, You et al. 2013) and suicidal behavior (e.g., Liu 2006).”

“Only three randomized controlled trials have demonstrated efficacy in temporarily reducing the risk for suicidal behavior among adolescents with a history of suicide attempts or self-harm (Asarnow et al. 2017, Esposito-Smythers et al. 2011, McCauley et al. 2018).”

“…females aged 14 to 18 years with a history of suicidal behavior or NSSI, or both, evinced lower resting RSA and excessive RSA withdrawal (i.e., greater release of SNS suppression) following exposure to evocative stimuli compared with controls (N = 23, ages 14–18 years) (Crowell et al. 2005).”

“…dialectical behavioral theories of suicide suggest that distorted thinking often leads to narrowed problem-solving abilities and risky or self-regulatory behavior, such as alcohol use or self-harm, that may make future suicidal behavior more likely (Linehan 1993, Rudd 2010, Spirito et al. 2012).”

“Nevertheless, prior research clearly has revealed NSSI as both a correlate and risk factor for suicidal ideation and behavior; yet the predictors and developmental course of NSSI differ from that of suicidal ideation and behaviors (see reviews by Fox et al. 2015 and Liu et al. 2017).”

“Notably, the prevalence of suicidal ideation, suicidal behavior, and death by suicide all increase dramatically during the adolescent transition, a unique period of developmental vulnerability for suicidal ideation and behaviors (Curtin et al. 2016, Glenn et al. 2017b, Kõlves & de Leo 2017).”

“For instance, a rich literature has demonstrated that depressive symptoms are associated with the development of hyporeactive responses to stress in the HPA axis (see Guerry & Hastings 2011 for a review).”

“Notably, the distinction between these constructs is sometimes unclear, particularly among youths who may not be able to articulate their intent to die before considering or engaging in suicidal behavior (Hawton et al. 2012, Prinstein 2008).”

“…individuals’ suicidal behavior on adolescents’ own suicidal behavior also have been well documented through research on suicide clusters (see Brent et al. 1989, Gould 1990, Gould et al. 1990, Joiner 1999, Phillips & Carstensen 1986), yielding best practice recommendations for the media…”

“…behavior on adolescents’ own suicidal behavior also have been well documented through research on suicide clusters (see Brent et al. 1989, Gould 1990, Gould et al. 1990, Joiner 1999, Phillips & Carstensen 1986), yielding best practice recommendations for the media and school personnel when…”

“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…”

“For instance, in some studies in adults, elevated baseline levels of cortisol have been associated with greater frequencies of suicidal behavior (Mann & Currier 2007).”

“…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.”

“…to acute stress that may help explain the proximal processes occurring in the moments between adolescents’ exposure to stress and their experience of suicidal ideation and behavior (see also Cha et al. 2018; Chang et al. 2016; Lutz et al. 2017; Pan et al. 2011, 2016; Turecki & Brent 2016).”

“…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…”

“…indicate that adults with a history of suicidal behavior show increased levels of interleukin6 (IL-6) (Janelidze et al. 2011, Lindqvist et al. 2009, Serafini et al. 2013), increased tumor necrosis factor-α (TNF-α) (Janelidze et al. 2011), decreased levels of IL-2 (Janelidze et al. 2011, Serafini…”

“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).”

“…own suicidal behavior also have been well documented through research on suicide clusters (see Brent et al. 1989, Gould 1990, Gould et al. 1990, Joiner 1999, Phillips & Carstensen 1986), yielding best practice recommendations for the media and school personnel when covering the death by…”

“Some studies have revealed that adults with a history of suicide attempts have more blunted cortisol reactivity to a Trier Social Stress Test (TSST) than those with only suicidal ideation history or than healthy controls (Melhem et al. 2016, O’Connor et al. 2017).”

“Neuringer (1964) noted that suicidal individuals were characterized by rigid thinking.”

“For instance, one study revealed that adolescents with major depressive disorder and suicidal ideation (N = 12) showed higher levels of interferon-γ compared with controls (N = 15) (Gabbay et al. 2009).”

“In adult samples, similar findings have emerged, suggesting decreased frontolimbic functional connectivity in individuals with suicidal ideation (Du et al. 2017, Kim et al. 2017, Minzenberg et al. 2015).”

“Recently, several theoretical (Glenn et al. 2017a), systematic (Cha et al. 2018), and meta-analytic reviews (Franklin et al. 2017, Glenn et al. 2018, Ribeiro et al. 2016) have been published on the topic of suicide, with one review by Cha and colleagues (2018) focusing specifically on youths.”

“…studies with combined samples of adults and youths, individuals with a lifetime history of suicidal behavior have had lower baseline levels or hair concentrations of cortisol compared with individuals with only suicidal ideation or with healthy controls (Keilp et al. 2016, Melhem et al. 2017).”

“A growing body of data also suggests that adolescents may be particularly susceptible toward the socialization of self-injury when a close friend endorses depressive symptoms, NSSI, or suicidal ideation and behavior (Bearman & Moody 2004, Kandel et al. 1991, Rew et al. 2001, Yoder 1999).”

“Suicidal ideation and behaviors are the most common mental health emergencies among adolescents (King et al. 2009).”

“Evidence from studies of adults also suggests that 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).”

“…to acute stress that may help explain the proximal processes occurring in the moments between adolescents’ exposure to stress and their experience of suicidal ideation and behavior (see also Cha et al. 2018; Chang et al. 2016; Lutz et al. 2017; Pan et al. 2011, 2016; Turecki & Brent 2016).”

“Notably, the prevalence of suicidal ideation, suicidal behavior, and death by suicide all increase dramatically during the adolescent transition, a unique period of developmental vulnerability for suicidal ideation and behaviors (Curtin et al. 2016, Glenn et al. 2017b, Kõlves & de Leo 2017).”

“…suicidal ideation appear to show abnormal resting state connectivity between PFC control regions and subcortical brain regions (Chase et al. 2017, Ordaz et al. 2018), potentially signaling a vulnerability to increased reactivity and decreased ability to modulate this reactivity when faced with a…”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript cytokines (Riis et al. 2014).”

“In adult samples, similar findings have emerged, suggesting decreased frontolimbic functional connectivity in individuals with suicidal ideation (Du et al. 2017, Kim et al. 2017, Minzenberg et al. 2015).”

“Polyamines are aliphatic molecules that are stress responsive (Gilad & Gilad 2003), have a major role in homeostatic regulation, and function to influence neurotransmitter systems, including catecholamines, γ-aminobutyric acid, glutamate, and nitric oxide (for an excellent review, see Gross &…”

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

“A growing body of data also suggests that adolescents may be particularly susceptible toward the socialization of self-injury when a close friend endorses depressive symptoms, NSSI, or suicidal ideation and behavior (Bearman & Moody 2004, Kandel et al. 1991, Rew et al. 2001, Yoder 1999).”

“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…”

“…through affiliations with other distressed teens, some emerging longitudinal evidence suggests that a friend’s suicide is a meaningful predictor of an adolescent’s own risk for future NSSI (Giletta et al. 2013, Prinstein et al. 2010, You et al. 2013) and suicidal behavior (e.g., Liu 2006).”

“…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).”

“Because work has demonstrated that 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), increased…”

“…deviations in chronic peer stress revealed that 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).”

“Our review also did not address a myriad of protective factors that may buffer the effects of risk on adolescents’ suicidal behavior; this remains a critically understudied yet important direction for research (see Gallagher & Miller 2018).”

“…the activity of intracellular, proinflammatory immune response genes [e.g., tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL1B)] that release protein molecules called cytokines, which are the primary mediators of systemic inflammation (Raison et al. 2006, Slavich et al. 2014).”

“…systems, and recent data suggest that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015,…”

“…with a history of suicidal ideation appear to show abnormal resting state connectivity between PFC control regions and subcortical brain regions (Chase et al. 2017, Ordaz et al. 2018), potentially signaling a vulnerability to increased reactivity and decreased ability to modulate this…”

“In adult samples, similar findings have emerged, suggesting decreased frontolimbic functional connectivity in individuals with suicidal ideation (Du et al. 2017, Kim et al. 2017, Minzenberg et al. 2015).”

“…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.”

“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…”

“…to acute stress that may help explain the proximal processes occurring in the moments between adolescents’ exposure to stress and their experience of suicidal ideation and behavior (see also Cha et al. 2018; Chang et al. 2016; Lutz et al. 2017; Pan et al. 2011, 2016; Turecki & Brent 2016).”

“In a cross-sectional study of depressed and/or self-harming adolescent girls, lower levels of cortisol after a dexamethasone suppression test (suggesting cortisol hyporeactivity) were associated with greater current suicidal ideation (Beauchaine et al. 2015).”

“…studies with combined samples of adults and youths, individuals with a lifetime history of suicidal behavior have had lower baseline levels or hair concentrations of cortisol compared with individuals with only suicidal ideation or with healthy controls (Keilp et al. 2016, Melhem et al. 2017).”

“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).”

“Similarly, changes in the HPA axis during adolescence result in heightened cortisol reactivity to acute stressors and a longer recovery relative to childhood and adult years (Gunnar et al. 2009, Romeo 2017).”

“For example, one study revealed that administration of the polyamine agmatine ameliorated experimentally (TNF-α)-induced depression-like behaviors in mice (Neis et al. 2014).”

“…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…”

“…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).”

“…adolescent girls’ increased experience of social stress, greater biological and emotional reactivity to interpersonal stress (Rose & Rudolph 2006, Stroud et al. 2017), and emerging data suggesting unique biological factors among females (i.e., circulating reproductive hormones) that may…”

“Adolescents’ bids to enhance or maintain this form of peer status frequently involve the use of overt or relational aggression strategies that often are cited as powerful predictors of adolescent suicide (Juvonen & Graham 2014, Massing-Schaffer et al. 2018).”

“…withdrawal (indexed via RSA decreases or RSA suppression) occurs almost instantaneously, thereby facilitating the fight-or-flight response of the SNS. Dynamic and flexible responses of RSA across environmental contexts are essential for adaptive physiological self-regulation (Hastings et al. 2014).”

“…that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015, Nederhof et al. 2015, Slavich & Irwin 2014).”

“…that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015, Nederhof et al. 2015, Slavich & Irwin 2014).”

“Altered polyamine-related genes, suggesting system dysregulation, also were revealed in a postmortem study of adults who died by suicide (Gross & Turecki 2013).”

“…systems, and recent data suggest that atypical presentations of these same systems have implications for understanding emotion dysregulation (Miller et al. 2017b, Tottenham et al. 2010) and a range of both internalizing and externalizing symptoms (Burghy et al. 2012, Chen et al. 2015,…”

“Another study demonstrated that children ages 7–11 years with a history of suicidal ideation and who had parents rated high on expressed negative emotion did not show flexible RSA responses to a stressful discussion, suggesting a poor adaptive stress response (James et al. 2017).”

“…through affiliations with other distressed teens, some emerging longitudinal evidence suggests that a friend’s suicide is a meaningful predictor of an adolescent’s own risk for future NSSI (Giletta et al. 2013, Prinstein et al. 2010, You et al. 2013) and suicidal behavior (e.g., Liu 2006).”

“…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…”

“However, slower recovery of RSA (indexed by lower resting RSA during recovery from the task) was associated with a prospective risk for this same self-injury composite over time (Wielgus et al. 2016).”

“…to acute stress that may help explain the proximal processes occurring in the moments between adolescents’ exposure to stress and their experience of suicidal ideation and behavior (see also Cha et al. 2018; Chang et al. 2016; Lutz et al. 2017; Pan et al. 2011, 2016; Turecki & Brent 2016).”

“There is also some preliminary evidence for autonomic dysregulation in insulin and glucagon secretion among individuals with a history of suicide attempt (Bendix et al. 2017).”

“…deviations in chronic peer stress revealed that 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).”

“Last, most theories offered to explain suicidal behavior have implicated interpersonal stress (e.g., conflict, loss) as a common factor that significantly enhances individuals’ risk (Miller & Prinstein, 2019).”

“Rather, they interact dynamically with stress (2, 3, 36, 37), a point underscored by the fact that stress is prominently featured in many leading STB (11, 20, 38) and NSSI (25, 39) theories.”