Adolescent suicide and testosterone

Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: A Hypothesis

Timothy R. Rice 1  and Leo Sher 1
  • 1 Department of Psychiatry, New York, USA
Timothy R. Rice
  • Corresponding author
  • Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA
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and Leo Sher
  • Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA
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  • degruyter.comGoogle Scholar

Abstract

Completed suicide is much more common in men than in women. Its incidence rises precipitously in adolescence. One biological hypothesis that accounts for the increased frequency of completed suicide in men is that the male sex hormone testosterone partially mediates the observed increase in suicide frequency among men. It is the aim of this communication to review the relevant literature and to describe putative biological mechanisms for this association. Specifically, we propose that the impairment wrought by of high levels of testosterone in the adolescent upon the emotion regulation system contribute to an account for these findings. Herein, we describe this neural system and the specific effects of testosterone upon the system. We conclude with a discussion of clinical implications and applications with an aim of stimulating further research.

  • 1.

    Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, et al. Suicide prevention strategies: a systematic review. J Am Med Assoc 2005;294:2064–74.

  • 2.

    Murphy S, Xu J, Kochanek K. Deaths: final data for 2010. vol 61, no 4. Hyattsville, MD: National vital statistics reports, 2013.

  • 3.

    Arsenault-Lapierre G, Kim C, Turecki G. Psychiatric diagnoses in 3275 suicides: a meta-analysis. BMC Psychiatry 2004;4:37.

  • 4.

    Bertolote JM, Fleischmann A, De Leo D, Wasserman D. Psychiatric diagnoses and suicide: revisiting the evidence. Crisis 2004;25:147–55.

  • 5.

    Möller-Leimkühler AM. The gender gap in suicide and premature death or: why are men so vulnerable? Eur Arch Psychiatry Clin Neurosci 2003;253:1–8.

  • 6.

    Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010-2011. Pediatrics 2013;131:548–58.

  • 7.

    Eaton D, Kann L, Kinchen S. Centers for disease control and prevention (CDC) youth risk behavior surveillance – United States, 2011. MMWR 2012;61:1–162.

  • 8.

    Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 2010;167:748–51.

  • 9.

    Insel TR. The NIMH Research Domain Criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry 2014;171:395–7.

  • 10.

    Varlinskaya EI, Vetter-O’Hagen CS, Spear LP. Puberty and gonadal hormones: role in adolescent-typical behavioral alterations. Horm Behav 2013;64:343–9.

  • 11.

    Markianos M, Tripodianakis J, Istikoglou C, Rouvali O, Christopoulos M, et al. Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident. Psychiatry Res 2009;170:82–5.

  • 12.

    Tripodianakis J, Markianos M, Rouvali O, Istikoglou C. Gonadal axis hormones in psychiatric male patients after a suicide attempt. Eur Arch Psychiatry Clin Neurosci 2007;257:135–9.

  • 13.

    Sher L. Testosterone and suicidal behavior. Expert Rev Neurother 2012;12:257–9.

  • 14.

    Perez-Rodriguez MM, Lopez-Castroman J, Martinez-Vigo M, Diaz-Sastre C, Ceverino A, et al. Lack of association between testosterone and suicide attempts. Neuropsychobiology 2011;63:125–30.

  • 15.

    Butterfield MI, Stechuchak KM, Connor KM, Davidson JRT, Wang C, et al. Neuroactive steroids and suicidality in posttraumatic stress disorder. Am J Psychiatry 2005;162:380–2.

  • 16.

    Roland B, Morris J, Zelhart P. Proposed relation of testosterone levels to male suicides and sudden deaths. Psychol Rep 1986;59:100–2.

  • 17.

    Thiblin I, Runeson B, Rajs J. Anabolic androgenic steroids and suicide. Ann Clin Psychiatry 1999;11:223–31.

  • 18.

    Barzman DH, Patel A, Sonnier L, Strawn JR. Neuroendocrine aspects of pediatric aggression: can hormone measures be clinically useful? Neuropsychiatr Dis Treat 2010;6:691–7.

  • 19.

    Scerbo AS, Kolko DJ. Salivary testosterone and cortisol in disruptive children: relationship to aggressive, hyperactive, and internalizing behaviors. J Am Acad Child Adolesc Psychiatry 1994;33:1174–84.

  • 20.

    Olweus D, Mattsson A, Schalling D, Löw H. Circulating testosterone levels and aggression in adolescent males: a causal analysis. Psychosom Med 1988;50:261–72.

  • 21.

    Constantino JN. Testosterone and aggression. J Am Acad Child Adolesc Psychiatry 1995;34:1–2.

  • 22.

    Rice TR, Sher L. Testosterone, emotion regulation and childhood aggression. Neuropsychiatry (London) 2013;3:267–70.

  • 23.

    Ladouceur CD. Neural systems supporting cognitive-affective interactions in adolescence: the role of puberty and implications for affective disorders. Front Integr Neurosci 2012;6:65.

  • 24.

    Ladouceur CD, Peper JS, Crone EA, Dahl RE. White matter development in adolescence: the influence of puberty and implications for affective disorders. Dev Cogn Neurosci 2012;2:36–54.

  • 25.

    Sato SM, Schulz KM, Sisk CL, Wood RI. Adolescents and androgens, receptors and rewards. Horm Behav 2008;53:647–58.

  • 26.

    Gross JJ. Emotion regulation: taking stock and moving forward. Emotion 2013;13:359–65.

  • 27.

    Mullin BC, Hinshaw SP. Emotion regulation and externalizing disorders in children and adolescents. Handbook of emotion regulation. New York, NY: Guilford Press, 2009.

  • 28.

    Silk JS, Steinberg L, Morris AS. Adolescents’ emotion regulation in daily life: links to depressive symptoms and problem behavior. Child Dev 2003;74:1869–80.

  • 29.

    Pisani AR, Wyman PA, Petrova M, Schmeelk-Cone K, Goldston DB, et al. Emotion regulation difficulties, youth-adult relationships, and suicide attempts among high school students in underserved communities. J Youth Adolesc 2013;42:807–20.

  • 30.

    Shaffer D, Garland A, Gould M, Fisher P, Trautman P. Preventing teenage suicide: a critical review. J Am Acad Child Adolesc Psychiatry 1988;27:675–87.

  • 31.

    Negron R, Piacentini J, Graae F, Davies M, Shaffer D. Microanalysis of adolescent suicide attempters and ideators during the acute suicidal episode. J Am Acad Child Adolesc Psychiatry 1997;36:1512–9.

  • 32.

    Kienhorst CW, de Wilde EJ, Diekstra RF, Wolters WH. Differences between adolescent suicide attempters and depressed adolescents. Acta Psychiatr Scand 1992;85:222–8.

  • 33.

    Tamás Z, Kovacs M, Gentzler AL, Tepper P, Gádoros J, et al. The relations of temperament and emotion self-regulation with suicidal behaviors in a clinical sample of depressed children in Hungary. J Abnorm Child Psychol 2007;35:640–52.

  • 34.

    Jacobson C, Batejan K, Kleinman M, Gould M. Reasons for attempting suicide among a community sample of adolescents. Suicide Life Threat Behav 2013;43:646–62.

  • 35.

    Rice T, Sher L. Neuroendocrinology of emotion regulation and suicide risk in adolescents. Neuropsychiatry (London) 2013;3:551–4.

  • 36.

    Rice T. Emotion regulation and adolescent suicide: a proposal for physician education. Int J Adolesc Med Health 2015;27:189–94.

  • 37.

    Linehan M. Cognitive-Behavioral treatment of borderline personality disorder. New York, NY: The Guilford Press, 1993.

  • 38.

    Gross JJ. Handbook of emotion reguation, 2nd ed. In: Gross J, editor. New York, NY: Guilford Press, 2014.

  • 39.

    Hoffman L, Rice T, Prout T. Manual for Regulation-focused psychotherapy for children with externalizing behaviors (RFP-C): a psychodynamic approach. New York, NY: Routledge, 2015.

  • 40.

    Mehta PH, Beer J. Neural mechanisms of the testosterone-aggression relation: the role of orbitofrontal cortex. J Cogn Neurosci 2010;22:2357–68.

  • 41.

    Farb NAS, Anderson AK, Segal ZV. The mindful brain and emotion regulation in mood disorders. Can J Psychiatry 2012;57:70–7.

  • 42.

    Hermann A, Bieber A, Keck T, Vaitl D, Stark R. Brain structural basis of cognitive reappraisal and expressive suppression. Soc Cogn Affect Neurosci 2014;9:1435–42.

  • 43.

    McRae K, Hughes B, Chopra S, Gabrieli JDE, Gross JJ, et al. The neural bases of distraction and reappraisal. J Cogn Neurosci 2010;22:248–62.

  • 44.

    Goldin PR, McRae K, Ramel W, Gross JJ. The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biol Psychiatry 2008;63:577–86.

  • 45.

    Pettit JW, Temple SR, Norton PJ, Yaroslavsky I, Grover KE, et al. Thought suppression and suicidal ideation: preliminary evidence in support of a robust association. Depress Anxiety 2009;26:758–63.

  • 46.

    Van Eck K, Ballard E, Hart S, Newcomer A, Musci R, et al. ADHD and suicidal ideation: the roles of emotion regulation and depressive symptoms among college students. J Atten Disord 2015;19:703–14.

  • 47.

    Gyurak A, Gross JJ, Etkin A. Explicit and implicit emotion regulation: a dual-process framework. Cogn Emot 2011;25:400–12.

  • 48.

    Ehring T, Tuschen-Caffier B, Schnülle J, Fischer S, Gross JJ. Emotion regulation and vulnerability to depression: spontaneous versus instructed use of emotion suppression and reappraisal. Emotion 2010;10:563–72.

  • 49.

    Etkin A, Prater KE, Hoeft F, Menon V, Schatzberg AF. Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. Am J Psychiatry 2010;167:545–54.

  • 50.

    Markham JA, Morris JR, Juraska JM. Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood. Neuroscience 2007;144:961–8.

  • 51.

    Geschwind N, Galaburda AM. Cerebral lateralization. Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Arch Neurol 1985;42:428–59.

  • 52.

    McManus IC, Bryden MP. Geschwind’s theory of cerebral lateralization: developing a formal, causal model. Psychol Bull 1991;110:237–53.

  • 53.

    Lyon G, Gadisseux J. Structural abnormalities of the brain in developmental disorders. In: Rutter M, Casaer P, editors. Biological risk factors for psychosocial disorders. Cambridge, MA: Cambridge University Press, 1991:1–19.

  • 54.

    Martel MM, Klump K, Nigg JT, Breedlove SM, Sisk CL. Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective. Horm Behav 2009;55:465–79.

  • 55.

    Martel MM, Nikolas M, Jernigan K, Friderici K, Nigg JT. Diversity in pathways to common childhood disruptive behavior disorders. J Abnorm Child Psychol 2012;40:1223–36.

  • 56.

    Martel MM. Sexual selection and sex differences in the prevalence of childhood externalizing and adolescent internalizing disorders. Psychol Bull 2013;139:1221–59.

  • 57.

    Shaw P, Stringaris A, Nigg J, Leibenluft E. Emotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry 2014;171:276–93.

  • 58.

    Hinshaw SP. Impulsivity, emotion regulation, and developmental psychopathology: specificity versus generality of linkages. Ann NY Acad Sci 2003;1008:149–59.

  • 59.

    Musser ED, Galloway-Long HS, Frick PJ, Nigg JT. Emotion regulation and heterogeneity in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2013;52:1–2.

  • 60.

    Cavanagh M, Quinn D, Duncan D, Graham T, Balbuena L. Oppositional defiant disorder is better conceptualized as a disorder of emotional regulation. J Atten Disord 2014;1–9.

  • 61.

    Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Taylor K, et al. Fetal testosterone influences sexually dimorphic gray matter in the human brain. J Neurosci 2012;32:674–80.

  • 62.

    Ackermann S, Spalek K, Rasch B, Gschwind L, Coynel D, et al. Testosterone levels in healthy men are related to amygdala reactivity and memory performance. Psychoneuroendocrinology 2012;37:1417–24.

  • 63.

    Volman I, Toni I, Verhagen L, Roelofs K. Endogenous testosterone modulates prefrontal-amygdala connectivity during social emotional behavior. Cereb Cortex 2011;21:2282–90.

  • 64.

    Van Wingen G, Mattern C, Verkes RJ, Buitelaar J, Fernández G. Testosterone reduces amygdala-orbitofrontal cortex coupling. Psychoneuroendocrinology 2010;35:105–13.

  • 65.

    Van Wingen GA, Ossewaarde L, Bäckström T, Hermans EJ, Fernández G. Gonadal hormone regulation of the emotion circuitry in humans. Neuroscience 2011;191:38–45.

  • 66.

    Denson TF, Ronay R, von Hippel W, Schira MM. Endogenous testosterone and cortisol modulate neural responses during induced anger control. Soc Neurosci 2013;8:165–77.

  • 67.

    Henckens MJAG, van Wingen GA, Joels M, Fernandez G. Time-dependent effects of corticosteroids on human amygdala processing. J Neurosci 2010;30:12725–32.

  • 68.

    Popma A, Vermeiren R, Geluk CAML, Rinne T, van den Brink W, et al. Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents. Biol Psychiatry 2007;61:405–11.

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