Recent findings on stress and anxiety in attention deficit hyperactivity disorder (ADHD) suggest that specific processes related to brain developmental disorganization could create a vulnerable background that increases sensitivity to stress stimuli from the psychosocial environment. These basic neurodevelopmental processes are closely related to the developmental mechanisms of primitive functions and their integration or disintegration. In this context, the psychopathological processes that manifest in ADHD are linked to the mechanisms of disturbed inhibitory functions that may cause incongruent neural interactions ("neural interference") between the more primitive functions and the higher levels of attentional and cognitive neural processes. These disturbed developmental processes may also determine increased sensitivity to stressful experiences that, in ADHD cases, could lead to the manifestations of various psychopathological symptoms such as disturbed attentional and motor functions, anxiety, and depression, among other cognitive and affective disturbances. These findings, based on previous research, suggest novel framework and hypothesis on how this neurodevelopment-based increased sensitivity to stress stimuli could manifest in the etiopathogenesis of ADHD in its relationship with cognitive, affective, and motor deficits.

Center for Neuropsychiatric Research of Traumatic Stress Department of Psychiatry and UHSL 1st Faculty of Medicine Charles University Prague Czechia

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Franz EA, Gillett G. John Hughlings Jackson’s evolutionary neurology: a unifying framework for cognitive neuroscience. Brain. (2011) 134:3114–20. doi: 10.1093/brain/awr218 PubMed DOI

Bob P, Konicarova J. ADHD, stress, and development. New York: Springer International Publishing; (2018).

Bob P, Konicarova J, Raboch J. Disinhibition of primitive reflexes in attention deficit and hyperactivity disorder: insight into specific mechanisms in girls and boys. Front Psychiatry. (2021) 12. doi: 10.3389/fpsyt.2021.430685 PubMed DOI PMC

Lee SH, Jung EM. Adverse effects of early-life stress: focus on the rodent neuroendocrine system. Neural Regeneration Res. (2024) 19:336–41. doi: 10.4103/1673-5374.377587 PubMed DOI PMC

Still G. The Goulstonian lectures on some abnormal psychical conditions in children. Lecture 1. Lancet. (1902) 1:1008–12.

Douglas VI. Stop, look and listen: the problem of sustained attention and impulse control in hyperactive and normal children. Can J Behav Sci. (1972) 4:259–82. doi: 10.1037/h0082313 DOI

Barkley RA. Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 3rd ed. New York, NY: Guilford Press; (2006).

Burd L, Kerbeshian J. Historical roots of ADHD. J Am Acad Child Adolesc Psychiatry. (1988) 27:262. doi: 10.1097/00004583-198803000-00029 PubMed DOI

Lange KW, Reichl S, Lange KM, Tucha L, Tucha O. The history of attention deficit hyperactivity disorder. Attention Deficit Hyperactivity Disord. (2010) 2:241–55. doi: 10.1007/s12402-010-0045-8 PubMed DOI PMC

Volkmar FR. Changing perspectives on ADHD. Am J Psychiatry. (2003) 160:1025–7. doi: 10.1176/appi.ajp.160.6.1025 PubMed DOI

American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-II). 4th edn. Washington DC: American Psychiatric Association; (2000). Text revision.

Hallowell EM, Ratey JJ. Delivered from distraction: Getting the most out of life with attention deficit disorder. New York: Ballantine Books; (2005).

Seidman LJ. Neuropsychological functioning in people with ADHD across the lifespan. Clin Psychol Rev. (2006) 26:466–85. doi: 10.1016/j.cpr.2006.01.004 PubMed DOI

Cherkasova M, Sulla EM, Dalena KL, Pondé MP, Hechtman L. Developmental course of attention deficit hyperactivity disorder and its predictors. J Can Acad Child Adolesc Psychiatry. (2013) 22:47–54. PubMed PMC

American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-V). 5th ed. Arlington, VA: American Psychiatric Publishing; (2014).

Biederman J, Mick E, Faraone SV. Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type. Am J Psychiatry. (2000) 157:816–8. doi: 10.1176/appi.ajp.157.5.816 PubMed DOI

Molina BSG, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, et al. . The MTA at 8 Years: Prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. (2009) 48:484–500. doi: 10.1097/CHI.0b013e31819c23d0 PubMed DOI PMC

Caye A, Spadini AV, Karam RG, Grevet EH, Rovaris DL, Bau CH, et al. . Predictors of persistence of ADHD into adulthood: a systematic review of the literature and meta-analysis. Eur Child Adolesc Psychiatry. (2016) 25:1151–9. doi: 10.1007/s00787-016-0831-8 PubMed DOI

Barkley RA, Murphy KR, Firscher M. ADHD in adults: What the Science Says. New York, NY: Guilford Press; (2008).

Biederman J, Monuteaux MC, Mick E, Spencer T, Wilens TE, Silva JM, et al. . Young adult outcome of attention deficit hyperactivity disorder: A controlled 10-year follow-up study. psychol Med. (2006) 36:167–79. doi: 10.1017/S0033291705006410 PubMed DOI

Klein RG, Mannuzza S, Olazagasti MA, Roizen E, Hutchison JA, Lashua EC, et al. . Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry. (2012) 69:1295–303. doi: 10.1001/archgenpsychiatry.2012.271 PubMed DOI PMC

Mannuzza S, Klein RG, Bessler A, Malloy P, Hynes ME. Educational and occupational outcome of hyperactive boys grown up. J Am Acad Child Adolesc Psychiatry. (1997) 36:1222–7. doi: 10.1097/00004583-199709000-00014 PubMed DOI

Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry. (1998) 155:493–8. doi: 10.1176/ajp.155.4.493 PubMed DOI

Weiss G, Hechtman L. Hyperactive children grown up: ADHD in children, adolescents, and adults. 2nd ed. New York, NY: Guilford Press; (1993).

Gair SL, Brown HR, Kang S, Grabell AS, Harvey EA. Early development of comorbidity between symptoms of ADHD and anxiety. Res Child Adolesc Psychopathol. (2021) 49:311–23. doi: 10.1007/s10802-020-00724-6 PubMed DOI PMC

Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, et al. . The prevalence and correlates of adult ADHD in the United States: Results from the national comorbidity survey replication. Am J Psychiatry. (2006) 163:716–23. doi: 10.1176/ajp.2006.163.4.716 PubMed DOI PMC

Sobanski E. Psychiatric comorbidity in adults with attentiondeficit/hyperactivity disorder (ADHD) Vol. 256. European Archives of Psychiatry and Clinical Neuroscience; (2006) p. i26–31. PubMed

Black DW, Arndt S, Hale N, Rogerson R. Use of the mini international neuropsychiatric interview (MINI) as a screening tool in prisons: Results of a preliminary study. J Am Acad Psychiatry Law. (2004) 32:158–62. PubMed

Gunter TD, Arndt S, Wenman G, Allen J, Loveless P, Sieleni B, et al. . Frequency of mental and addictive disorders among 320 men and women entering the iowa prison system: Use of the MINI-plus. J Am Acad Psychiatry Law. (2008) 36:27–34. PubMed

Brocki KC, Nyberg L, Thorell LB, Bohlin G. Early concurrent and longitudinal symptoms of ADHD and ODD: Relations to different types of inhibitory control and working memory. J Child Psychol Psychiatry. (2007) 48:1033–41. doi: 10.1111/j.1469-7610.2007.01811.x PubMed DOI

LeBlanc N, Boivin M, Dionne G, Brendgen M, Vitaro F, Tremblay R, et al. . The development of hyperactive–impulsive behaviors during the preschool years: The predictive validity of parental assessments. J Abnormal Child Psychol. (2008) 36:977–87. doi: 10.1007/s10802-008-9227-7 PubMed DOI

Wahlstedt C, Thorell LB, Bohlin G. ADHD symptoms and executive function impairment: Early predictors of later behavioral problems. Dev Neuropsychol. (2008) 33:160–78. doi: 10.1080/87565640701884253 PubMed DOI

Chronis AM, Lahey BB, Pelham WE, Jr., Williams SH, Baumann BL, Kipp H, et al. . Maternal depression and early positive parenting predict future conduct problems in young children with attention-deficit/hyperactivity disorder. Dev Psychol. (2007) 43:70–82. doi: 10.1037/0012-1649.43.1.70 PubMed DOI

Biederman J, Petty CR, Clarke A, Lomedico A, Faraone SV. Predictors of persistent ADHD: An 11-year follow-up study. J Psychiatr Res. (2011) 45:150–5. doi: 10.1016/j.jpsychires.2010.06.009 PubMed DOI PMC

Swanson JM, Hinshaw SP, Arnold LE, Gibbons RD, Marcus SUE, Hur K, et al. . Secondary evaluations of MTA 36-month outcomes: Propensity score and growth mixture model analyses. J Am Acad Child Adolesc Psychiatry. (2007) 46:1003–14. doi: 10.1097/CHI.0b013e3180686d63 PubMed DOI

Punski-Hoogervorst JL, Engel-Yeger B, Avital A. Attention deficits as a key player in the symptomatology of posttraumatic stress disorder: A review. J Neurosci Res. (2023) 101:1068–85. doi: 10.1002/jnr.v101.7 PubMed DOI

Nigg JT, Willcutt EG, Doyle AE, Sonuga-Barke EJ. Causal heterogeneity in attention-deficit/hyperactivity disorder: do we need neuropsychologically impaired subtypes? Biol Psychiatry. (2005) 57:1224–30. doi: 10.1016/j.biopsych.2004.08.025 PubMed DOI

Hofmann W, Schmeichel BJ, Baddeley AD. Executive functions and self-regulation. Trends Cogn Sci. (2012) 16:174–80. doi: 10.1016/j.tics.2012.01.006 PubMed DOI

Martinez L, Prada E, Satler C, Tavares MC, Tomaz C. Executive dysfunctions: the role in attention deficit hyperactivity and post-traumatic stress neuropsychiatric disorders. Front Psychol. (2016) 7:1230. doi: 10.3389/fpsyg.2016.01230 PubMed DOI PMC

Castellanos FX, Sonuga-Barke EJ, Milham MP, Tannock R. Characterizing cognition in ADHD: beyond executive dysfunction. Trends Cogn Sci. (2006) 10:117–23. doi: 10.1016/j.tics.2006.01.011 PubMed DOI

Toplak ME, Jain U, Tannock R. Executive and motivational processes in adolescents with attention deficit-hyperactivity disorder (ADHD). Behav Brain Functions. (2005) 1:8. doi: 10.1186/1744-9081-1-8 PubMed DOI PMC

Antonini TN, Becker SP, Tamm L, Epstein JN. Hot and cool executive functions in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. J Int Neuropsychol Soc. (2015) 21:584–95. doi: 10.1017/S1355617715000752 PubMed DOI PMC

Sonuga-Barke EJ. The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev. (2003) 27:593–604. doi: 10.1016/j.neubiorev.2003.08.005 PubMed DOI

Solanto MV, Abikoff H, Sonuga-Barke E, Schachar R, Logan GD, Wigal T, et al. . The ecological validity of delay aversion and response inhibition as measures of impulsivity in AD/HD a supplement to the NIMH multi-modal treatment study of AD/HD. J Abnormal Child Psychol. (2001) 29:215–28. doi: 10.1023/A:1010329714819 PubMed DOI

Nigg J. Is AD/HD a disinhibitory disorder? psychol Bull. (2001) 127:571–98. PubMed

Johnson KA, Robertson IH, Kelly SP, Silk TJ, Barry E, Daibhis A, et al. . Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention. Neuropsychologia. (2007) 45:2234–45. doi: 10.1016/j.neuropsychologia.2007.02.019 PubMed DOI PMC

Sugar J, Ford JD. Peritraumatic reactions and posttraumatic stress disorder in psychiatrically impaired youth. J Traumatic Stress. (2012) 25:41–9. doi: 10.1002/jts.21668 PubMed DOI

Adler LA, Kunz M, Chua HC, Rotrosen J, Resnick SG. Attention deficit/hyperactivity disorder in adult patients with posttraumatic stress disorder (PTSD): Is ADHD a vulnerability factor? J Attentional Disord. (2004) 8:11–6. doi: 10.1177/108705470400800102 PubMed DOI

Daud A, Rydelius PA. Comorbidity/overlapping between ADHD and PTSD in relation to IQ among children of traumatized/non-traumatized parents. J Attentional Disord. (2009) 13:188–96. doi: 10.1177/1087054708326271 PubMed DOI

Henry JP. Psychological and physiological responses to stress: the right hemisphere and the hypothalamo-pituitary-adrenal axis, an inquiry into problems of human bonding. Integr Physiol Behav Sci. (1993) 28:369–87. doi: 10.1007/BF02690935 PubMed DOI

Henry JP. Psychological and physiological responses to stress: the right hemisphere and the hypothalamo-pituitary-adrenal axis, an inquiry into problems of human bonding. Acta Physiologica Scandinavica. (1997) 161:10–25. PubMed

Hasler G, van der Veen JW, Grillon C, Drevets WC, Shen J. Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy. Am J Psychiatry. (2010) 167:1226–31. doi: 10.1176/appi.ajp.2010.09070994 PubMed DOI PMC

Andermann AA. Hughlings Jackson’s deductive science of the nervous system: a product of his thought collective and formative years. Neurology. (1997) 48:471–81. doi: 10.1212/WNL.48.2.471 PubMed DOI

Jacyna LS. Process and progress: John Hughlings Jackson’s philosophy of science. Brain. (2011) 134:3121–6. doi: 10.1093/brain/awr236 PubMed DOI

Teicher MH, Tomoda A, Andersen SL. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann New York Acad Sci. (2006) 1071:313–23. PubMed

Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol. (2009) 19:207–12. doi: 10.1016/j.conb.2009.05.009 PubMed DOI PMC

Kolb B, Gibb R. Brain plasticity and behaviour in the developing brain. J Can Acad Child Adolesc Psychiatry. (2011) 20:265–76. PubMed PMC

Allen MC, Capute AJ. The evolution of primitive reflexes in extremely premature infants. Pediatr Res. (1986) 20:1284–9. doi: 10.1203/00006450-198612000-00018 PubMed DOI

Zafeiriou DI. Primitive reflexes and postural reactions in the neurodevelopmental examination. Pediatr Neurol. (2004) 31:1–8. doi: 10.1016/j.pediatrneurol.2004.01.012 PubMed DOI

Sanders RD, Gillig PM. Reflexes in psychiatry. Innov Clin Neurosci. (2011) 8:24–9. PubMed PMC

Ellis MD, Drogos J, Carmona C, Keller T, Dewald JP. Neck rotation modulates flexion synergy torques indicating an ipsilateral reticulospinal source for impairment in stroke. J Neurophysiol. (2012) 108:3096–104. doi: 10.1152/jn.01030.2011 PubMed DOI PMC

Touwen BCL. Primitive reflexes-conceptional or semantic problem. In: Prechtl HFR, editor. Continuity of neural functions from prenatal to postnatal life. Spastics International Medical Publications, Oxford, Great Britain: (1984).

Capute AJ, Accardo PJ. Developmental disabilities in infancy and childhood. Baltimore, MD: Paul Brooks; (1991).

Niklasson M. The relation between postural movement and bilateral motor integration: Comment on Lin, et al., (2012). Perceptual Motor Skills. (2013) 117:647–50. PubMed

Polatajko HJ. Developmental Coordination Disorder (DCD): alias, the clumsy child syndrome. In: Whitmore K, Hart H, Willems G, editors. A neurodevelopmental approach to specific learning disorders. Mac Keith Press, London: (1999). p. 119–33.

Youssef HA, Waddington JL. Primitive (developmental) reflexes and diffuse cerebral dysfunction in schizophrenia and bipolar affective disorder: overrepresentation in patients with tardive dyskinesia. Biol Psychiatry. (1988) 23:791–6. doi: 10.1016/0006-3223(88)90067-4 PubMed DOI

Links KA, Merims D, Binns MA, Freedman M, Chow TW. Prevalence of primitive reflexes and Parkinsonian signs in dementia. Can J Neurological Sci. (2010) 37:601–7. doi: 10.1017/S0317167100010763 PubMed DOI

Nicolson SE, Chabon B, Larsen KA, Kelly SE, Potter AW, Stern TA. Primitive reflexes associated with delirium: a prospective trial. Psychosomatics. (2011) 52:507–12. doi: 10.1016/j.psym.2011.06.008 PubMed DOI

Keshavan MS, Yeragani VK. Primitive reflexes in psychiatry. Lancet. (1987) 1:1264. doi: 10.1016/S0140-6736(87)92714-0 PubMed DOI

Bubier JL, Drabick DA. Co-occurring anxiety and disruptive behavior disorders: The roles of anxious symptoms, reactive aggression, and shared risk processes. Clin Psychol Rev. (2009) 29:658–69. doi: 10.1016/j.cpr.2009.08.005 PubMed DOI PMC

Overgaard KR, Aase H, Torgersen S, Zeiner P. Co-occurrence of ADHD and anxiety in preschool children. J Attention Disord. (2016) 20:573–80. doi: 10.1177/1087054712463063 PubMed DOI

Buderath P, Gärtner K, Frings M, Christiansen H, Schoch B, Konczak J, et al. . Postural and gait performance in children with attention deficit/hyperactivity disorder. Gait Posture. (2009) 29:249–54. doi: 10.1016/j.gaitpost.2008.08.016 PubMed DOI

D’Agati E, Casarelli L, Pitzianti MB, Pasini A. Overflow movements and white matter abnormalities in ADHD. Prog Neuropsychopharmacol Biol Psychiatry. (2010) 34:441–5. doi: 10.1016/j.pnpbp.2010.01.013 PubMed DOI

Ghanizadeh A. Predictors of postural stability in children with ADHD. J Attention Disord. (2011) 15:604–10. doi: 10.1177/1087054710370936 PubMed DOI

Arnsten AF. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CNS Drugs. (2009) 23:33–41. doi: 10.2165/00023210-200923000-00005 PubMed DOI

Shaw P, Rabin C. New insights into attention-deficit/hyperactivity disorder using structural neuroimaging. Curr Psychiatry Rep. (2009) 11:393–8. doi: 10.1007/s11920-009-0059-0 PubMed DOI

Makris N, Biederman J, Monuteaux MC, Seidman LJ. Towards conceptualizing a neural systems-based anatomy of attention-deficit/hyperactivity disorder. Dev Neurosci. (2009) 31:36–49. doi: 10.1159/000207492 PubMed DOI PMC

Berquin PC, Giedd JN, Jacobsen LK, Hamburger SD, Krain AL, Rapoport JL, et al. . Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study. Neurology. (1998) 50:1087–93. doi: 10.1212/WNL.50.4.1087 PubMed DOI

Baillieux H, De Smet HJ, Paquier PF, De Deyn PP, Marien P. Cerebellar neurocognition: insights into the bottom of the brain. Clin Neurol Neurosurg. (2008) 110:763–73. doi: 10.1016/j.clineuro.2008.05.013 PubMed DOI

O’Halloran CJ, Kinsella GJ, Storey E. The cerebellum and neuropsychological functioning: a critical review. J Clin Exp Neuropsychol. (2012) 34:35–56. doi: 10.1080/13803395.2011.614599 PubMed DOI