Irritability is a common and impairing clinical presentation in children and adolescents. Despite its significant public health impact, irritability remains an elusive construct. Chronic and severe irritability is the primary symptom of the new DSM-5 diagnosis, disruptive mood dysregulation disorder (DMDD). However, empirical and clinical approaches to irritability are in their relative infancy, and questions regarding the validity of the DMDD diagnosis have been raised. Moreover, irritability is a trait distributed continuously in youth, thereby fitting within the National Institute of Mental Health Research Domain Criteria initiative. Thus, there are opportunities for scientific review and integration. Accordingly, the goals of this review include () clarifying the definitions of irritability, incorporating clinical and translational animal work; () reviewing the historical context surrounding the study of irritability; () reviewing the prevalence, clinical correlates, and longitudinal course of irritability; () presenting behavioral and neurobiological findings associated with irritability; and () exploring treatment options and proposing future directions for research.


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Literature Cited

  1. Adleman NE, Fromm SJ, Razdan V, Kayser R, Dickstein DP. et al. 2012. Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder. J. Child Psychol. Psychiatry 53:1149–56 [Google Scholar]
  2. Adleman NE, Kayser R, Dickstein D, Blair RJR, Pine D, Leibenluft E. 2011. Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry 50:1173–85 [Google Scholar]
  3. Althoff RR, Crehan ET, He JP, Burstein M, Hudziak JJ, Merikangas KR. 2016. Disruptive mood dysregulation disorder at ages 13–18: results from the National Comorbidity Survey–Adolescent Supplement. J. Child Adolesc. Psychopharmacol. 26:107–13 [Google Scholar]
  4. Althoff RR, Kuny-Slock AV, Verhulst FC, Hudziak JJ, van der Ende J. 2014. Classes of oppositional-defiant behavior: concurrent and predictive validity. J. Child Psychol. Psychiatry 55:1162–71 [Google Scholar]
  5. Althoff RR, Verhulst FC, Rettew DC, Hudziak JJ, van der Ende J. 2010. Adult outcomes of childhood dysregulation: a 14-year follow-up study. J. Am. Acad. Child Adolesc. Psychiatry 49:1105–16 [Google Scholar]
  6. Ambrosini PJ, Bennett DS, Elia J. 2013. Attention deficit hyperactivity disorder characteristics: II. Clinical correlates of irritable mood. J. Affect. Disord. 145:70–76 [Google Scholar]
  7. Am. Psychiatr. Assoc. 2013. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am. Psychiatr. Assoc, 5th ed.. [Google Scholar]
  8. Amsel A. 1958. The role of frustrative nonreward in noncontinuous reward situations. Psychol. Bull. 55:102–19 [Google Scholar]
  9. Avenevoli S, Blader JC, Leibenluft E. 2015. Irritability in youth: an update. J. Am. Acad. Child Adolesc. Psychiatry 54:881–83 [Google Scholar]
  10. Axelson D, Findling RL, Fristad MA, Kowatch RA, Youngstrom EA. et al. 2012. Examining the proposed disruptive mood dysregulation disorder diagnosis in children in the Longitudinal Assessment of Manic Symptoms study. J. Clin. Psychol. 73:1342–50 [Google Scholar]
  11. Bar-Haim Y, Lamy D, Pergamin L, Bakermans-Kranenburg MJ, van IJzendoorn MH. 2007. Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study. Psychol. Bull. 133:1–24 [Google Scholar]
  12. Basten M, Tiemeier H, Althoff RR, van de Schoot R, Jaddoe VW. et al. 2016. The stability of problem behavior across the preschool years: an empirical approach in the general population. J. Abnorm. Child Psychol. 44:393–404 [Google Scholar]
  13. Bebko G, Bertocci M, Chase H, Dwojak A, Bonar L. et al. 2015. Decreased amygdala-insula resting state connectivity in behaviorally and emotionally dysregulated youth. Psychiatry Res 231:77–86 [Google Scholar]
  14. Bebko G, Bertocci MA, Fournier JC, Hinze AK, Bonar L. et al. 2014. Parsing dimensional versus diagnostic category-related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the Longitudinal Assessment of Manic Symptoms study. JAMA Psychiatry 71:71–80 [Google Scholar]
  15. Berkowitz L. 1989. Frustration-aggression hypothesis: examination and reformulation. Psychol. Bull. 106:59–73 [Google Scholar]
  16. Biederman J, Klein RG, Pine DS, Klein DF. 1998. Resolved: Mania is mistaken for ADHD in prepubertal children. J. Am. Acad. Child Adolesc. Psychiatry 37:1091–96; discussion 96–99 [Google Scholar]
  17. Blader JC, Carlson GA. 2007. Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996–2004. Biol. Psychiatry 62:107–14 [Google Scholar]
  18. Blader JC, Pliszka SR, Jensen PS, Schooler NR, Kafantaris V. 2010. Stimulant-responsive and stimulant-refractory aggressive behavior among children with ADHD. Pediatrics 126:e796–806 [Google Scholar]
  19. Blader JC, Pliszka SR, Kafantaris V, Sauder C, Posner J. et al. 2016. Prevalence and treatment outcomes of persistent negative mood among children with attention-deficit/hyperactivity disorder and aggressive behavior. J. Child Adolesc. Psychopharmacol. 26:164–73 [Google Scholar]
  20. Blair RJ. 2010. Psychopathy, frustration, and reactive aggression: the role of ventromedial prefrontal cortex. Brit. J. Psychol. 101:383–99 [Google Scholar]
  21. Brotman MA, Kassem L, Reising MM, Guyer AE, Dickstein DP. et al. 2007. Parental diagnoses in youth with narrow phenotype bipolar disorder or severe mood dysregulation. Am. J. Psychiatry 164:1238–41 [Google Scholar]
  22. Brotman MA, Kircanski K, Stringaris A, Pine DS, Leibenluft E. 2017. Irritability in youths: a translational model. Am. J. Psychiatry.
  23. Brotman MA, Rich BA, Guyer AE, Lunsford JR, Horsey SE. et al. 2010. Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Am. J. Psychiatry 167:61–69 [Google Scholar]
  24. Brotman MA, Schmajuk M, Rich BA, Dickstein DP, Guyer AE. et al. 2006. Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biol. Psychiatry 60:991–97 [Google Scholar]
  25. Burke JD, Boylan K, Rowe R, Duku E, Stepp SD. et al. 2014. Identifying the irritability dimension of ODD: application of a modified bifactor model across five large community samples of children. J. Abnorm. Psychol. 123:841–51 [Google Scholar]
  26. Burokas A, Gutiérrez-Cuesta J, Martín-García E, Maldonado R. 2012. Operant model of frustrated expected reward in mice. Addict. Biol. 17:770–82 [Google Scholar]
  27. Buss AH, Durkee A. 1957. An inventory for assessing different kinds of hostility. J. Consult. Psychol. 21:343–49 [Google Scholar]
  28. Caprara GV, Cinanni V, D'Imperio G, Passerini S, Renzi P, Travaglia G. 1985. Indicators of impulsive aggression: present status of research on irritability and emotional susceptibility scales. Personal. Individ. Differ. 6:665–74 [Google Scholar]
  29. Caprara GV, Paciello M, Gerbino M, Cugini C. 2007. Individual differences conducive to aggression and violence: trajectories and correlates of irritability and hostile rumination through adolescence. Aggress. Behav. 33:359–74 [Google Scholar]
  30. Carver CS, Harmon-Jones E. 2009. Anger is an approach-related affect: evidence and implications. Psychol. Bull. 135:183–204 [Google Scholar]
  31. Coccaro EF, Bergeman CS, Kavoussi RJ, Seroczynski AD. 1997. Heritability of aggression and irritability: a twin study of the Buss-Durkee aggression scales in adult male subjects. Biol. Psychiatry 41:273–84 [Google Scholar]
  32. Coccaro EF, Lee RJ, Kavoussi RJ. 2009. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J. Clin. Psychiatry 70:653–62 [Google Scholar]
  33. Conner KR, Meldrum S, Wieczorek WF, Duberstein PR, Welte JW. 2004. The association of irritability and impulsivity with suicidal ideation among 15- to 20-year-old males. Suicide Life Threat. Behav. 34:363–73 [Google Scholar]
  34. Connor DF, Glatt SJ, Lopez ID, Jackson D, Melloni RH Jr. 2002. Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. J. Am. Acad. Child Adolesc. Psychiatry 41:253–61 [Google Scholar]
  35. Cools R, Altamirano L, D'Esposito M. 2006. Reversal learning in Parkinson's disease depends on medication status and outcome valence. Neuropsychologia 44:1663–73 [Google Scholar]
  36. Cools R, Clark L, Owen AM, Robbins TW. 2002. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J. Neurosci. 22:4563–67 [Google Scholar]
  37. Copeland WE, Angold A, Costello EJ, Egger H. 2013. Prevalence, comorbidity, and correlates of DSM-5 proposed disruptive mood dysregulation disorder. Am. J. Psychiatry 170:173–79 [Google Scholar]
  38. Copeland WE, Brotman MA, Costello EJ. 2015. Normative irritability in youth: developmental findings from the Great Smoky Mountains Study. J. Am. Acad. Child Adolesc. Psychiatry 54:635–42 [Google Scholar]
  39. Copeland WE, Shanahan L, Egger H, Angold A, Costello EJ. 2014. Adult diagnostic and functional outcomes of DSM-5 disruptive mood dysregulation disorder. Am. J. Psychiatry 171:668–74 [Google Scholar]
  40. Cornacchio D, Crum KI, Coxe S, Pincus DB, Comer JS. 2016. Irritability and severity of anxious symptomatology among youth with anxiety disorders. J. Am. Acad. Child Adolesc. Psychiatry 55:54–61 [Google Scholar]
  41. Costa VD, Tran VL, Turchi J, Averbeck BB. 2015. Reversal learning and dopamine: a Bayesian perspective. J. Neurosci. 35:2407–16 [Google Scholar]
  42. Crick NR, Dodge KA. 1994. A review and reformulation of social information-processing mechanisms in children's social adjustment. Psychol. Bull. 115:74–101 [Google Scholar]
  43. Davenport JW, Thompson CI. 1965. The Amsel frustration effect in monkeys. Anim. Behav. 3:481–82 [Google Scholar]
  44. Deveney CM, Connolly ME, Haring CT, Bones BL, Reynolds RC. et al. 2013. Neural mechanisms of frustration in chronically irritable children. Am. J. Psychiatry 170:1186–94 [Google Scholar]
  45. Dickstein DP, Nelson EE, McClure EB, Grimley ME, Knopf L. et al. 2007. Cognitive flexibility in phenotypes of pediatric bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry 46:341–55 [Google Scholar]
  46. Dickstein DP, Rich BA, Binstock AB, Pradella AG, Towbin KE. et al. 2005. Comorbid anxiety in phenotypes of pediatric bipolar disorder. J. Child Adolesc. Psychopharmacol. 15:534–48 [Google Scholar]
  47. Dickstein DP, Towbin KE, Van Der Veen JW, Rich BA, Brotman MA. et al. 2009. Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation. J. Child Adolesc. Psychopharmacol. 19:61–73 [Google Scholar]
  48. Dimmock PW, Wyatt KM, Jones PW, O'Brien PM. 2000. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. Lancet 356:1131–36 [Google Scholar]
  49. Dodge KA. 1980. Social cognition and children's aggressive behavior. Child Dev 51:162–70 [Google Scholar]
  50. Dollard J, Doob L, Miller N, Mowrer O, Sears R. 1939. Frustration and Aggression New Haven, CT: Yale Univ. Press
  51. Dougherty LR, Smith VC, Bufferd SJ, Carlson GA, Stringaris A. et al. 2014. DSM-5 disruptive mood dysregulation disorder: correlates and predictors in young children. Psychol. Med. 44:2339–50 [Google Scholar]
  52. Dougherty LR, Smith VC, Bufferd SJ, Kessel EM, Carlson GA, Klein DN. 2016. Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later. Psychol. Med. 46:1103–14 [Google Scholar]
  53. Dougherty LR, Smith VC, Bufferd SJ, Stringaris A, Leibenluft E. et al. 2013. Preschool irritability: longitudinal associations with psychiatric disorders at age 6 and parental psychopathology. J. Am. Acad. Child Adolesc. Psychiatry 52:1304–13 [Google Scholar]
  54. Eley TC. 1999. Behavioral genetics as a tool for developmental psychology: anxiety and depression in children and adolescents. Clin. Child Fam. Psychol. Rev. 2:21–36 [Google Scholar]
  55. Fanselow MS. 1994. Neural organization of the defensive behavior system responsible for fear. Psychon. Bull. Rev. 1:429–38 [Google Scholar]
  56. Fava M, Hwang I, Rush AJ, Sampson N, Walters EE, Kessler RC. 2010. The importance of irritability as a symptom of major depressive disorder: results from the National Comorbidity Survey Replication. Mol. Psychiatry 15:856–67 [Google Scholar]
  57. Fava M, Rosenbaum JF. 1999. Anger attacks in patients with depression. J. Clin. Psychiatry 60:21–24 [Google Scholar]
  58. Fernández de la Cruz L, Simonoff E, McGough JJ, Halperin JM, Arnold LE, Stringaris A. 2015. Treatment of children with attention-deficit/hyperactivity disorder (ADHD) and irritability: results from the Multimodal Treatment Study of Children with ADHD (MTA). J. Am. Acad. Child Adolesc. Psychiatry 54:62–70 [Google Scholar]
  59. Finger EC, Marsh AA, Blair KS, Reid ME, Sims C. et al. 2011. Disrupted reinforcement signaling in the orbitofrontal cortex and caudate in youths with conduct disorder or oppositional defiant disorder and a high level of psychopathic traits. Am. J. Psychiatry 168:152–62 [Google Scholar]
  60. Freeman AJ, Youngstrom EA, Youngstrom JK, Findling RL. 2016. Disruptive mood dysregulation disorder in a community mental health clinic: prevalence, comorbidity and correlates. J. Child Adolesc. Psychopharmacol. 26:123–30 [Google Scholar]
  61. Fristad MA, Wolfson H, Algorta GP, Youngstrom EA, Arnold LE. et al. 2016. Disruptive mood dysregulation disorder and bipolar disorder not otherwise specified: fraternal or identical twins. J. Child Adolesc. Psychopharmacol. 26:138–46 [Google Scholar]
  62. Gagne JR, Goldsmith HH. 2011. A longitudinal analysis of anger and inhibitory control in twins from 12 to 36 months of age. Dev. Sci. 14:112–24 [Google Scholar]
  63. Gatzke-Kopp LM, Beauchaine TP, Shannon KE, Chipman J, Fleming AP. et al. 2009. Neurological correlates of reward responding in adolescents with and without externalizing behavior disorders. J. Abnorm. Psychol. 118:203–13 [Google Scholar]
  64. Guyer AE, McClure EB, Adler AD, Brotman MA, Rich BA. et al. 2007. Specificity of facial expression labeling deficits in childhood psychopathology. J. Child Psychol. Psychiatry 48:863–71 [Google Scholar]
  65. Hommer RE, Meyer A, Stoddard J, Connolly ME, Mogg K. et al. 2014. Attention bias to threat faces in severe mood dysregulation. Depress. Anxiety 31:559–65 [Google Scholar]
  66. Hulvershorn LA, Mennes M, Castellanos FX, Di Martino A, Milham MP. et al. 2014. Abnormal amygdala functional connectivity associated with emotional lability in children with attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 53:351–61 [Google Scholar]
  67. Insel TR. 2009. Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch. Gen. Psychiatry 66:128–33 [Google Scholar]
  68. Insel TR, Cuthbert B, Garvey M, Heinssen R, Pine DS. et al. 2010. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167:748–51 [Google Scholar]
  69. James A, Hoang U, Seagroatt V, Clacey J, Goldacre M, Leibenluft E. 2014. A comparison of American and English hospital discharge rates for pediatric bipolar disorder, 2000 to 2010. J. Am. Acad. Child Adolesc. Psychiatry 53:614–24 [Google Scholar]
  70. Jensen PS, Youngstrom EA, Steiner H, Findling RL, Meyer RE. et al. 2007. Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: implications for medication studies. J. Am. Acad. Child Adolesc. Psychiatry 46:309–22 [Google Scholar]
  71. Ji N, Findling RL. 2015. An update on pharmacotherapy for autism spectrum disorder in children and adolescents. Curr. Opin. Psychiatry 28:91–101 [Google Scholar]
  72. Judd LL, Schettler PJ, Coryell W, Akiskal HS, Fiedorowicz JG. 2013. Overt irritability/anger in unipolar major depressive episodes: past and current characteristics and implications for long-term course. JAMA Psychiatry 70:1171–80 [Google Scholar]
  73. Kazdin AE. 2010. Problem-solving skills training and parent management training for oppositional defiant disorder and conduct disorder. Evidence-Based Psychotherapies for Children and Adolescents J Weisz, A Kazdin 211–26 New York: Guilford Press, 2nd ed.. [Google Scholar]
  74. Kessel EM, Dougherty LR, Kujawa A, Hajcak G, Carlson GA, Klein DN. 2016. Longitudinal associations between preschool disruptive mood dysregulation disorder symptoms and neural reactivity to monetary reward during preadolescence. J. Child Adolesc. Psychopharmacol. 26:131–37 [Google Scholar]
  75. Kim S, Boylan K. 2016. Effectiveness of antidepressant medications for symptoms of irritability and disruptive behaviors in children and adolescents. J. Child Adolesc. Psychopharmacol. 26:694–704 [Google Scholar]
  76. Krieger FV, Pheula GF, Coelho R, Zeni T, Tramontina S. et al. 2011. An open-label trial of risperidone in children and adolescents with severe mood dysregulation. J. Child Adolesc. Psychopharmacol. 21:237–43 [Google Scholar]
  77. Krieger FV, Polanczyk VG, Goodman R, Rohde LA, Graeff-Martins AS. et al. 2013. Dimensions of oppositionality in a Brazilian community sample: testing the DSM-5 proposal and etiological links. J. Am. Acad. Child Adolesc. Psychiatry 52:389–400 [Google Scholar]
  78. Lamm C, Granic I, Zelazo PD, Lewis MD. 2011. Magnitude and chronometry of neural mechanisms of emotion regulation in subtypes of aggressive children. Brain Cogn 77:159–69 [Google Scholar]
  79. Leadbeater BJ, Homel J. 2015. Irritable and defiant sub-dimensions of ODD: their stability and prediction of internalizing symptoms and conduct problems from adolescence to young adulthood. J. Abnorm. Child Psychol. 43:407–21 [Google Scholar]
  80. LeDoux JE, Pine DS. 2016. Using neuroscience to help understand fear and anxiety: a two-system framework. Am. J. Psychiatry 173:1083–93 [Google Scholar]
  81. Leibenluft E. 2011. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am. J. Psychiatry 168:129–42 [Google Scholar]
  82. Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS. 2003. Defining clinical phenotypes of juvenile mania. Am. J. Psychiatry 160:430–37 [Google Scholar]
  83. Leibenluft E, Cohen P, Gorrindo T, Brook JS, Pine DS. 2006. Chronic versus episodic irritability in youth: a community-based, longitudinal study of clinical and diagnostic associations. J. Child Adolesc. Psychopharmacol. 16:456–66 [Google Scholar]
  84. Leibenluft E, Stoddard J. 2013. The developmental psychopathology of irritability. Dev. Psychopathol. 25:1473–87 [Google Scholar]
  85. Liu Y, Zhan X, Li W, Han H, Wang H. et al. 2015. The trait anger affects conflict inhibition: a Go/Nogo ERP study. Front. Hum. Neurosci. 8:1076 [Google Scholar]
  86. Lochman JE, Boxmeyer CL, Powell NP, Barry TD, Pardini DA. 2010. Anger control training for aggressive youths. Evidence-Based Psychotherapies for Children and Adolescents AE Kazdin, JR Weisz 227–42 New York: Guilford Press [Google Scholar]
  87. Luna B, Garver KE, Urban TA, Lazar NA, Sweeney JA. 2004. Maturation of cognitive processes from late childhood to adulthood. Child Dev 75:1357–72 [Google Scholar]
  88. Marcus RN, Owen R, Kamen L, Manos G, McQuade RD. et al. 2009. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J. Am. Acad. Child Adolesc. Psychiatry 48:1110–19 [Google Scholar]
  89. Margulies DM, Weintraub S, Basile J, Grover PJ, Carlson GA. 2012. Will disruptive mood dysregulation disorder reduce false diagnosis of bipolar disorder in children?. Bipolar Disord 14:488–96 [Google Scholar]
  90. Mayes SD, Mathiowetz C, Kokotovich C, Waxmonsky J, Baweja R. et al. 2015. Stability of disruptive mood dysregulation disorder symptoms (irritable-angry mood and temper outbursts) throughout childhood and adolescence in a general population sample. J. Abnorm. Child Psychol. 43:1543–49 [Google Scholar]
  91. Mayes SD, Waxmonsky JD, Calhoun SL, Bixler EO. 2016. Disruptive mood dysregulation disorder symptoms and association with oppositional defiant and other disorders in a general population child sample. J. Child Adolesc. Psychopharmacol. 26:101–6 [Google Scholar]
  92. McCracken JT, McGough J, Shah B, Cronin P, Hong D. et al. 2002. Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 347:314–21 [Google Scholar]
  93. Mitchell RH, Timmins V, Collins J, Scavone A, Iskric A, Goldstein BI. 2016. Prevalence and correlates of disruptive mood dysregulation disorder among adolescents with bipolar disorder. J. Child Adolesc. Psychopharmacol. 26:147–53 [Google Scholar]
  94. Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. 2007. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch. Gen. Psychiatry 64:1032–39 [Google Scholar]
  95. Nakamura K, Hikosaka O. 2006. Role of dopamine in the primate caudate nucleus in reward modulation of saccades. J. Neurosci. 26:5360–69 [Google Scholar]
  96. Nock MK, Kazdin AE, Hiripi E, Kessler RC. 2007. Lifetime prevalence, correlates, and persistence of oppositional defiant disorder: results from the National Comorbidity Survey Replication. J. Child Psychol. Psychiatry 48:703–13 [Google Scholar]
  97. O'Doherty J, Dayan P, Schultz J, Deichmann R, Friston K, Dolan RJ. 2004. Dissociable roles of ventral and dorsal striatum in instrumental conditioning. Science 304:452–54 [Google Scholar]
  98. Papini MR, Dudley RT. 1997. Consequences of surprising reward omissions. Rev. Gen. Psychol. 1:175–97 [Google Scholar]
  99. Patterson GR. 1975. Families: Applications of Social Learning to Family Life Champaign, IL: Research Press
  100. Pawliczek CM, Derntl B, Kellermann T, Gur RC, Schneider F, Habel U. 2013. Anger under control: neural correlates of frustration as a function of trait aggression. PLOS ONE 8:e78503 [Google Scholar]
  101. Penton-Voak IS, Thomas J, Gage SH, McMurran M, McDonald S, Munafo MR. 2013. Increasing recognition of happiness in ambiguous facial expressions reduces anger and aggressive behavior. Psychol. Sci. 24:688–97 [Google Scholar]
  102. Pereira F, Mitchell T, Botvinick M. 2009. Machine learning classifiers and fMRI: a tutorial overview. NeuroImage 45:S199–209 [Google Scholar]
  103. Perlman SB, Jones BM, Wakschlag LS, Axelson D, Birmaher B, Phillips ML. 2015. Neural substrates of child irritability in typically developing and psychiatric populations. Dev. Cogn. Neurosci. 14:71–80 [Google Scholar]
  104. Perlman SB, Luna B, Hein TC, Huppert TJ. 2014. fNIRS evidence of prefrontal regulation of frustration in early childhood. NeuroImage 85:Pt. 1326–34 [Google Scholar]
  105. Peterson BS, Zhang H, Santa Lucia R, King RA, Lewis M. 1996. Risk factors for presenting problems in child psychiatric emergencies. J. Am. Acad. Child Adolesc. Psychiatry 35:1162–73 [Google Scholar]
  106. Pickles A, Aglan A, Collishaw S, Messer J, Rutter M, Maughan B. 2010. Predictors of suicidality across the life span: the Isle of Wight study. Psychol. Med. 40:1453–66 [Google Scholar]
  107. Pilling S, Gould N, Whittington C, Taylor C, Scott S. 2013. Recognition, intervention, and management of antisocial behaviour and conduct disorders in children and young people: summary of NICE-SCIE guidance. BMJ 346:f1298 [Google Scholar]
  108. Posner J, Rauh V, Gruber A, Gat I, Wang Z, Peterson BS. 2013. Dissociable attentional and affective circuits in medication-naive children with attention-deficit/hyperactivity disorder. Psychiatry Res 213:24–30 [Google Scholar]
  109. Regier DA, Narrow WE, Clarke DE, Kraemer HC, Kuramoto SJ. et al. 2013. DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am. J. Psychiatry 170:59–70 [Google Scholar]
  110. Rich BA, Carver FW, Holroyd T, Rosen HR, Mendoza JK. et al. 2011. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation. J. Psychiatr. Res. 45:1283–94 [Google Scholar]
  111. Rich BA, Schmajuk M, Perez-Edgar KE, Fox NA, Pine DS, Leibenluft E. 2007. Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. Am. J. Psychiatry 164:309–17 [Google Scholar]
  112. Roberson-Nay R, Leibenluft E, Brotman MA, Myers J, Larsson H. et al. 2015. Longitudinal stability of genetic and environmental influences on irritability: from childhood to young adulthood. Am. J. Psychiatry 172:657–64 [Google Scholar]
  113. Roy AK, Lopes V, Klein RG. 2014. Disruptive mood dysregulation disorder: a new diagnostic approach to chronic irritability in youth. Am. J. Psychiatry 171:918–24 [Google Scholar]
  114. Runions KC, Stewart RM, Moore J, Martinez Ladino Y, Rao P, Zepf FD. 2016. Disruptive mood dysregulation disorder in ICD-11: a new disorder or ODD with a specifier for chronic irritability. Eur. Child Adolesc. Psychiatry 25:331–32 [Google Scholar]
  115. Ryan TJ, Watson P. 1968. Frustrative nonreward theory applied to children's behavior. Psychol. Bull. 69:111–25 [Google Scholar]
  116. Savage J, Verhulst B, Copeland W, Althoff RR, Lichtenstein P, Roberson-Nay R. 2015. A genetically informed study of the longitudinal relation between irritability and anxious/depressed symptoms. J. Am. Acad. Child Adolesc. Psychiatry 54:377–84 [Google Scholar]
  117. Schultz W. 2002. Getting formal with dopamine and reward. Neuron 36:241–63 [Google Scholar]
  118. Scott S, O'Connor TG. 2012. An experimental test of differential susceptibility to parenting among emotionally-dysregulated children in a randomized controlled trial for oppositional behavior. J. Child Psychol. Psychiatry 53:1184–93 [Google Scholar]
  119. Scott S, Sylva K, Doolan M, Price J, Jacobs B. et al. 2010. Randomised controlled trial of parent groups for child antisocial behaviour targeting multiple risk factors: the SPOKES project. J. Child Psychol. Psychiatry 51:48–57 [Google Scholar]
  120. Shaw P, Stringaris A, Nigg J, Leibenluft E. 2014. Emotion dysregulation in attention deficit hyperactivity disorder. Am. J. Psychiatry 171:276–93 [Google Scholar]
  121. Snaith RP, Taylor CM. 1985. Irritability: definition, assessment and associated factors. Br. J. Psychiatry 147:127–36 [Google Scholar]
  122. Spielberger CD, Reheiser EC, Sydeman SJ. 1995. Measuring the experience, expression, and control of anger. Issues Compr. Pediatr. Nurs. 18:207–32 [Google Scholar]
  123. Stoddard J, Hsu D, Reynolds RC, Brotman MA, Ernst M. et al. 2015. Aberrant amygdala intrinsic functional connectivity distinguishes youths with bipolar disorder from those with severe mood dysregulation. Psychiatry Res 231:120–25 [Google Scholar]
  124. Stoddard J, Sharif-Askary B, Harkins EA, Frank HR, Brotman MA. et al. 2016. An open pilot study of training hostile interpretation bias to treat disruptive mood dysregulation disorder. J. Child Adolesc. Psychopharmacol. 26:49–57 [Google Scholar]
  125. Stoddard J, Stringaris A, Brotman MA, Montville D, Pine DS, Leibenluft E. 2014. Irritability in child and adolescent anxiety disorders. Depress. Anxiety 31:566–73 [Google Scholar]
  126. Stringaris A. 2011. Irritability in children and adolescents: a challenge for DSM-5. Eur. Child Adolesc. Psychiatry 20:61–66 [Google Scholar]
  127. Stringaris A. 2013. Editorial: the new DSM is coming—it needs tough love…. J. Child Psychol. Psychiatry 54:501–2 [Google Scholar]
  128. Stringaris A, Baroni A, Haimm C, Brotman M, Lowe CH. et al. 2010. Pediatric bipolar disorder versus severe mood dysregulation: risk for manic episodes on follow-up. J. Am. Acad. Child Adolesc. Psychiatry 49:397–405 [Google Scholar]
  129. Stringaris A, Cohen P, Pine DS, Leibenluft E. 2009. Adult outcomes of youth irritability: a 20-year prospective community-based study. Am. J. Psychiatry 166:1048–54 [Google Scholar]
  130. Stringaris A, Goodman R. 2009a. Longitudinal outcome of youth oppositionality: irritable, headstrong, and hurtful behaviors have distinctive predictions. J. Am. Acad. Child Adolesc. Psychiatry 48:404–12 [Google Scholar]
  131. Stringaris A, Goodman R. 2009b. Three dimensions of oppositionality in youth. J. Child Psychol. Psychiatry 50:216–23 [Google Scholar]
  132. Stringaris A, Goodman R, Ferdinando S, Razdan V, Muhrer E. et al. 2012a. The Affective Reactivity Index: a concise irritability scale for clinical and research settings. J. Child Psychol. Psychiatry 53:1109–17 [Google Scholar]
  133. Stringaris A, Taylor E. 2015. Disruptive Mood: Irritability in Children and Adolescents Oxford, UK: Oxford Univ. Press
  134. Stringaris A, Zavos H, Leibenluft E, Maughan B, Eley TC. 2012b. Adolescent irritability: phenotypic associations and genetic links with depressed mood. Am. J. Psychiatry 169:47–54 [Google Scholar]
  135. Sukhodolsky DG, Scahill L. 2012. Cognitive-Behavioral Therapy for Anger and Aggression in Children New York: Guilford Press
  136. Sukhodolsky DG, Smith SD, McCauley SA, Ibrahim K, Piasecka JB. 2016a. Behavioral interventions for anger, irritability, and aggression in children and adolescents. J. Child Adolesc. Psychopharmacol. 26:58–64 [Google Scholar]
  137. Sukhodolsky DG, Vander Wyk BC, Eilbott JA, McCauley SA, Ibrahim K. et al. 2016b. Neural mechanisms of cognitive-behavioral therapy for aggression in children and adolescents: design of a randomized controlled trial within the National Institute for Mental Health Research Domain Criteria construct of frustrative non-reward. J. Child Adolesc. Psychopharmacol. 26:38–48 [Google Scholar]
  138. Thomas LA, Brotman MA, Muhrer EJ, Rosen BH, Bones BL. et al. 2012. Parametric modulation of neural activity by emotion in youth with bipolar disorder, youth with severe mood dysregulation, and healthy volunteers. Arch. Gen. Psychiatry 69:1257–66 [Google Scholar]
  139. Thomas LA, Kim P, Bones BL, Hinton KE, Milch HS. et al. 2013. Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder. NeuroImage Clin 2:637–45 [Google Scholar]
  140. Tobler PN, Fiorillo CD, Schultz W. 2005. Adaptive coding of reward value by dopamine neurons. Science 307:1642–45 [Google Scholar]
  141. Tseng WL, Thomas LA, Harkins E, Pine DS, Leibenluft E, Brotman MA. 2016. Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation. Soc. Cogn. Affect. Neurosci. 11:78–88 [Google Scholar]
  142. Tufan E, Topal Z, Demir N, Taskiran S, Savci U. et al. 2016. Sociodemographic and clinical features of disruptive mood dysregulation disorder: a chart review. J. Child Adolesc. Psychopharmacol. 26:94–100 [Google Scholar]
  143. Van Honk J, Tuiten A, de Haan E, vann de Hout M, Stam H. 2001. Attentional biases for angry faces: relationships to trait anger and anxiety. Cogn. Emot. 15:279–97 [Google Scholar]
  144. Vidal-Ribas P, Brotman MA, Valdivieso I, Leibenluft E, Stringaris A. 2016. The status of irritability in psychiatry: a conceptual and quantitative review. J. Am. Acad. Child Adolesc. Psychiatry 55:556–70 [Google Scholar]
  145. Wakschlag LS, Estabrook R, Petitclerc A, Henry D, Burns JL. et al. 2015. Clinical implications of a dimensional approach: the normal:abnormal spectrum of early irritability. J. Am. Acad. Child Adolesc. Psychiatry 54:626–34 [Google Scholar]
  146. Wakschlag LS, Choi SW, Carter AS, Hullsiek H, Burns J, McCarthy K. et al. 2012. Defining the developmental parameters of temper loss in early childhood: implications for developmental psychopathology. J. Child Psychol. Psychiatry 53:111099–108 [Google Scholar]
  147. Waxmonsky J, Pelham WE, Gnagy E, Cummings MR, O'Connor B. et al. 2008. The efficacy and tolerability of methylphenidate and behavior modification in children with attention-deficit/hyperactivity disorder and severe mood dysregulation. J. Child Adolesc. Psychopharmacol. 18:573–88 [Google Scholar]
  148. Waxmonsky JG, Waschbusch DA, Belin P, Li T, Babocsai L. et al. 2016. A randomized clinical trial of an integrative group therapy for children with severe mood dysregulation. J. Am. Acad. Child Adolesc. Psychiatry 55:196–207 [Google Scholar]
  149. Whelan YM, Leibenluft E, Stringaris A, Barker ED. 2015. Pathways from maternal depressive symptoms to adolescent depressive symptoms: the unique contribution of irritability symptoms. J. Child Psychol. Psychiatry 56:1092–100 [Google Scholar]
  150. Whelan YM, Stringaris A, Maughan B, Barker ED. 2013. Developmental continuity of oppositional defiant disorder subdimensions at ages 8, 10, and 13 years and their distinct psychiatric outcomes at age 16 years. J. Am. Acad. Child Adolesc. Psychiatry 52:961–69 [Google Scholar]
  151. Wiggins JL, Brotman MA, Adleman NE, Kim P, Oakes AH. et al. 2016. Neural correlates of irritability in disruptive mood dysregulation and bipolar disorders. Am. J. Psychiatry 173:722–30 [Google Scholar]
  152. Wiggins JL, Mitchell C, Stringaris A, Leibenluft E. 2014. Developmental trajectories of irritability and bidirectional associations with maternal depression. J. Am. Acad. Child Adolesc. Psychiatry 53:1191–205 [Google Scholar]
  • Article Type: Review Article
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