Recent advances in understanding the neurobiology of pediatric functional neurological disorder

References

• Leary PM Conversion disorder in childhood-diagnosed too late, investigated too much. J R Soc Med. 2003;96:436–438 PubMed. doi: 10.1258/jrsm.96.9.436
   PubMed Web of Science ®Google Scholar
• Operto FF, Coppola G, Mazza R, et al. Psychogenic nonepileptic seizures in pediatric population: A review. Brain Behav. 2019;9(12):e01406 PubMed. doi: 10.1002/brb3.1406
   PubMed Web of Science ®Google Scholar
• Jungilligens J, Michaelis R, Popkirov S Misdiagnosis of prolonged psychogenic non-epileptic seizures as status epilepticus: epidemiology and associated risks. J Neurol Neurosurg Psychiatry. 2021;92(12):1341–1345. doi: 10.1136/jnnp-2021-326443
   PubMed Web of Science ®Google Scholar
• Sigurdardottir KR, Olafsson E. Incidence of psychogenic seizures in adults: a population-based study in Iceland. Epilepsia. 1998;39(7):749–752. doi: 10.1111/j.1528-1157.1998.tb01161.x
   PubMed Web of Science ®Google Scholar
• Villagrán A, Eldøen G, Duncan R, et al. Incidence and prevalence of psychogenic nonepileptic seizures in a Norwegian county: a 10‐year population‐based study. Epilepsia (Copenhagen). 2021;62(7):1528–535. doi: 10.1111/epi.16949
   PubMed Web of Science ®Google Scholar
• Hansen AS, Rask CU, Rodrigo-Domingo M, et al. Incidence rates and characteristics of pediatric onset psychogenic nonepileptic seizures. Pediatr Res. 2020;88(5):796–803. doi: 10.1038/s41390-020-0945-z
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Nunn KP, Rose D, et al. Conversion disorder in Australian pediatric practice. J Am Acad Child Adolesc Psychiatry. 2007;46(1):68–75. doi: 10.1097/01.chi.0000242235.83140.1f
   PubMed Web of Science ®Google Scholar
• Ani C, Reading R, Lynn R, et al. Incidence and 12-month outcome of non-transient childhood conversion disorder in the UK and Ireland. Br J Psychiatry. 2013;202:413–418 PubMed. doi: 10.1192/bjp.bp.112.116707
   PubMed Web of Science ®Google Scholar
• Shephard B A war of nerves: soldiers and psychiatrists in the twentieth century. Cambridge Mass: Harvard University Press; 2001.
   Google Scholar
• Leff JP. Psychiatry around the globe: a transcultural view. 1st ed. (NY): Dekker; 1981.
   Google Scholar
• Da Costa JM On irritable heart; a clinical study of a form of functional cardiac disorder and its consequences. Am J Med Sci. 1871;121:2–52. doi: 10.1097/00000441-187101000-00001
   Google Scholar
• Kardiner A. The traumatic neuroses of war. Washington (DC): National Research Council; 1941.
   Google Scholar
• Crocq L Les Traumatismes Psychiques de Guerre. Paris: Odile Jacob; 1999.
   Google Scholar
• Kozlowska K, Scher S, Helgeland H. Historical context: terminology (online supplement 1.1). In: Dallos R Vetere A, editors Functional somatic symptoms in children and adolescents: the stress-system approach to assessment and treatment palgrave macmillan’s counselling and psychotherapy series. London: Palgrave Macmillan; 2020.
   Google Scholar
• Kozlowska K, Walker P, McLean L, et al. Fear and the defense cascade: clinical implications and management. Harv Rev Psychiatry. 2015;23(4):263–287. 10.1097/HRP.0000000000000065
   PubMed Web of Science ®Google Scholar
• Grossman D. On combat: the psychology and physiology of deadly conflict in war and in peace. 1st ed. ed. Christensen LW, editor. Milstadt (Ill): PPCT Research Publications; 2004.
   Google Scholar
• Heyman I, Liang H, Hedderly T. COVID-19 related increase in childhood tics and tic-like attacks. Arch Dis Child. 2021;106(5):420–421. doi: 10.1136/archdischild-2021-321748
   Web of Science ®Google Scholar
• Hull M, Parnes M. Tics and TikTok: functional tics spread through social media. Mov Disord Clin Pract. 2021;8(8):1248–1252. doi: 10.1002/mdc3.13267
   PubMed Web of Science ®Google Scholar
• Pringsheim T, Ganos C, McGuire JF, et al. Rapid onset functional tic-like behaviors in young females during the COVID-19 pandemic. Mov Disord. 2021;36(12):2707–2713. doi: 10.1002/mds.28778
   PubMed Web of Science ®Google Scholar
• Pringsheim T, Martino D. Rapid onset of functional tic-like behaviours in young adults during the COVID-19 pandemic. Eur J Neurol. 2021;28(11):3805–3808. doi: 10.1111/ene.15034
   PubMed Web of Science ®Google Scholar
• Buts S, Duncan M, Owen T, et al. Paediatric tic-like presentations during the COVID-19 pandemic. Arch Dis Child. 2022;107(3):e17. doi: 10.1136/archdischild-2021-323002
   PubMed Web of Science ®Google Scholar
• Muller-Vahl KR, Pisarenko A, Jakubovski E, et al. Stop that! It’s not Tourette’s but a new type of mass sociogenic illness. Brain. 2022;476–480. 145 2 10.1093/brain/awab316
   PubMed Web of Science ®Google Scholar
• Paulus T, Baumer T, Verrel J, et al. Pandemic tic-like behaviors following social media consumption. Mov Disord. 2021;36(12):2932–2935. doi: 10.1002/mds.28800
   PubMed Web of Science ®Google Scholar
• Han VX, Kozlowska K, Kothur K, et al. Rapid onset functional tic-like behaviours in children and adolescents during COVID-19: clinical features, assessment and biopsychosocial treatment approach. J Paediatr Child Health. 2022;58(7):1181–1187.10.1111/jpc.15932
   PubMed Web of Science ®Google Scholar
• Nilles C, Pringsheim TM, Martino D. The recent surge of functional movement disorders: social distress or greater awareness? Curr Opin Neurol. 2022;35(4):485–493. doi: 10.1097/WCO.0000000000001074
   PubMed Web of Science ®Google Scholar
• Martino D, Hedderly T, Murphy T, et al. The spectrum of functional tic-like behaviours: data from an international registry. Eur J Neurol. 2023;30(2):334–343. doi: 10.1111/ene.15611
   PubMed Web of Science ®Google Scholar
• Guerriero RM, Pier DB, de Gusmao CM, et al. Increased pediatric functional neurological symptom disorders after the Boston marathon bombings: a case series. Pediatr Neurol. 2014;51(5):619–623. doi: 10.1016/j.pediatrneurol.2014.07.011
   PubMed Web of Science ®Google Scholar
• Carson A, Lehn A, Ludwig L, et al. Explaining functional disorders in the neurology clinic: a photo story. Pract Neurol. 2015;16:56–61 PubMed. doi: 10.1136/practneurol-2015-001242
   Google Scholar
• Stone J. Functional neurological disorders: the neurological assessment as treatment. Pract Neurol. 2016;16(1):7–17. doi: 10.1136/practneurol-2015-001241
   PubMedGoogle Scholar
• Kozlowska K, Mohammad S. Functional neurological disorder in children and adolescents: assessment and treatment. In: Sivaswamy L, Kamat D, editors Symptom based approach to pediatric neurology. Switzerland AG: Springer Nature; 2022. p. 683–724.
   Google Scholar
• Viswanathan N, Benbadis SR. The diagnosis of functional seizures. VideoEEG in the context of a complete clinical picture remains the gold standard for diagnosis of functional seizures. Pract Neurol. 2022;March/April:63–66.
   Google Scholar
• Ricci L, Boscarino M, Assenza G, et al. Clinical utility of home videos for diagnosing epileptic seizures: a systematic review and practical recommendations for optimal and safe recording. Neurol Sci. 2021;42(4):1301–1309. doi: 10.1007/s10072-021-05040-5
   PubMed Web of Science ®Google Scholar
• Beniczky SA, Fogarasi A, Neufeld M, et al. Seizure semiology inferred from clinical descriptions and from video recordings. How accurate are they? Epilepsy Behav. 2012;24(2):213–215. doi: 10.1016/j.yebeh.2012.03.036
   PubMed Web of Science ®Google Scholar
• Avbersek A, Sisodiya S. Does the primary literature provide support for clinical signs used to distinguish psychogenic nonepileptic seizures from epileptic seizures? J Neurol Neurosurg Psychiatry. 2010;81(7):719–725. doi: 10.1136/jnnp.2009.197996
   PubMed Web of Science ®Google Scholar
• Syed TU, LaFrance WC Jr., Kahriman ES, et al. Can semiology predict psychogenic nonepileptic seizures? A prospective study. Ann Neurol. 2011;69(6):997–1004. doi: 10.1002/ana.22345
   PubMed Web of Science ®Google Scholar
• LaFrance WC Jr., Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International league against epilepsy nonepileptic seizures task force. Epilepsia. 2013;54(11):2005–2018. doi: 10.1111/epi.12356
   PubMed Web of Science ®Google Scholar
• Seneviratne U, Minato E, Paul E How reliable is ictal duration to differentiate psychogenic nonepileptic seizures from epileptic seizures? Epilepsy Behav. 2017;66:127–131 PubMed.10.1016/j.yebeh.2016.10.024
   PubMed Web of Science ®Google Scholar
• Brigo F. Psychogenic nonepileptic seizures: we know what they are not. But do we know what they are? Epilepsy Behav. 2017;67:139. 10.1016/j.yebeh.2016.10.030
   PubMed Web of Science ®Google Scholar
• Muthusamy S, Seneviratne U, Ding C, et al. Using semiology to classify epileptic seizures vs psychogenic nonepileptic seizures: a meta-analysis. Neurol Clin Pract. 2022;12(3):234–247. doi: 10.1212/CPJ.0000000000001170
   PubMedGoogle Scholar
• Popkirov S, Reuber M, Kozlowska K. Communicating diagnosis of Functional/Dissociative seizures. Functional/Dissociative seizure task force. Psychiatry Commission. International League Against Epilepsy (ILAE) 2022 Oct 8. Available from: https://www.youtube.com/watch?v=oq6JhqPq5d
   Google Scholar
• Capra F. The web of life: a new synthesis of mind and matter. London: Flamingo; 1997.
   Google Scholar
• Jackson JH. The Croonian Lectures on evolution and dissolution of the nervous system. Br Med J. 1884;1(1213):591–593. 10.1136/bmj.1.1213.591
   PubMedGoogle Scholar
• MacLean PD. The triune brain in evolution: role in paleocerebral functions. (NY): Plenum Press; 1990p. xxiv, 672 p.
   Google Scholar
• Knyazev GG. EEG delta oscillations as a correlate of basic homeostatic and motivational processes. Neurosci Biobehav Rev. 2012;36(1):677–95. doi: 10.1016/j.neubiorev.2011.10.002
   PubMed Web of Science ®Google Scholar
• Arnsten AF. Stress weakens prefrontal networks: molecular insults to higher cognition. Nat Neurosci. 2015;18(10):1376–1385. doi: 10.1038/nn.4087
   PubMed Web of Science ®Google Scholar
• Raut RV, Snyder AZ, Mitra A, et al. Global waves synchronize the brain’s functional systems with fluctuating arousal. Sci Adv. 2021;7(30). doi: 10.1126/sciadv.abf2709
   PubMed Web of Science ®Google Scholar
• Agorastos A, Pervanidou P, Chrousos GP, et al. Developmental trajectories of early life stress and trauma: a narrative review on neurobiological aspects beyond stress system dysregulation. Front Psychiatry. 2019;10:118
   PubMed Web of Science ®Google Scholar
• Pervanidou P, Chrousos GP. Early-life stress: from neuroendocrine mechanisms to stress-related disorders. Horm Res Paediatr. 2018;89(5):372–379. doi: 10.1159/000488468
   PubMed Web of Science ®Google Scholar
• McEwen BS, Flier JS, Underhill LH. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338(3):171–179. doi: 10.1056/NEJM199801153380307
   PubMed Web of Science ®Google Scholar
• McEwen BS, Gray JD, Nasca C. 60 Years of neuroendocrinology: redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. J Endocrinol. 2015;226(2):T67–T83. doi: 10.1530/JOE-15-0121
   PubMed Web of Science ®Google Scholar
• Zannas AS, Chrousos GP. Epigenetic programming by stress and glucocorticoids along the human lifespan. Mol Psychiatry. 2017;22(5):640–646. doi: 10.1038/mp.2017.35
   PubMed Web of Science ®Google Scholar
• Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study. Am J Prev Med. 1998;14(4):245–258. doi: 10.1016/S0749-3797(98)00017-8
   PubMed Web of Science ®Google Scholar
• Boyce WT, Levitt P, Martinez FD, et al. Genes, environments, and time: the biology of adversity and resilience. Pediatrics. 2021;147(2). doi: 10.1542/peds.2020-1651
   Web of Science ®Google Scholar
• Sterling P, Eyer J. Allostatis: a new paradigm to explain arousal pathology. In: Fisher S, Reason J, editors Handbook of life stress, cognition and health. Chichester: Wiley; 1988. p. 629–649.
   Google Scholar
• McEwen BS, Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern Med. 1993;153(18):2093–2101. 10.1001/archinte.1993.00410180039004
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Scher S, Helgeland H. Functional somatic symptoms in children and adolescents: a stress-system approach to assessment and treatment. London: Palgrave Macmillan; 2020.
   Google Scholar
• McCraty R, Childre D. Coherence: bridging personal, social, and global health. Altern Ther Health Med. 2010;16(4):10–24.
   PubMed Web of Science ®Google Scholar
• Hallett M, Aybek S, Dworetzky BA, et al. Functional neurological disorder: new subtypes and shared mechanisms. Lancet Neurol. 2022;21(6):537–550. doi: 10.1016/S1474-4422(21)00422-1
   PubMed Web of Science ®Google Scholar
• Edwards MJ, Adams RA, Brown H, et al. A Bayesian account of ‘hysteria’. Brain. 2012;135(11):3495–3512. doi: 10.1093/brain/aws129
   PubMed Web of Science ®Google Scholar
• Kleckner IR, Zhang J, Touroutoglou A, et al. Evidence for a large-scale brain system supporting allostasis and interoception in humans. Nat Human Behav. 2017;1(5). 10.1038/s41562-017-0069
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. 5th edition, text revision. ed. Washington (DC): APA Publishing; 2022.
   Google Scholar
• Vachon-Presseau E, Centeno MV, Ren W, et al. The emotional brain as a predictor and amplifier of chronic pain. J Dent Res. 2016;95(6):605–612. doi: 10.1177/0022034516638027
   PubMed Web of Science ®Google Scholar
• Polese D, Belli A, Esposito D, et al. Psychological disorders, adverse childhood experiences and parental psychiatric disorders in children affected by headache: a systematic review. Neurosci Biobehav Rev. 2022;140:104798. doi: 10.1016/j.neubiorev.2022.104798
   PubMed Web of Science ®Google Scholar
• Raucci U, Boni A, Evangelisti M, et al. Lifestyle modifications to help prevent headache at a developmental age. Front Neurol. 2021;11:618375. doi: 10.3389/fneur.2020.618375
   PubMed Web of Science ®Google Scholar
• Papetti L, Alaimo Di Loro P, Tarantino S, et al. I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children. Cephalalgia. 2020;40(13):1459–1473. doi: 10.1177/0333102420965139
   PubMed Web of Science ®Google Scholar
• Hyams JS, Di Lorenzo C, Miguel Saps M, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology. 2016;150(6):1456–68.e2. doi: 10.1053/j.gastro.2016.02.015
   Web of Science ®Google Scholar
• Drossman DA, Hasler WL. Rome IV-Functional GI disorders: disorders of gut-brain interaction. Gastroenterology. 2016;150(6):1257–1261. doi: 10.1053/j.gastro.2016.03.035
   PubMed Web of Science ®Google Scholar
• Raucci U, Borrelli O, Di Nardo G, et al. Cyclic vomiting syndrome in children. Front Neurol. 2020;11:583425. doi: 10.3389/fneur.2020.583425
   PubMed Web of Science ®Google Scholar
• Vassilopoulos A, Mohammad S, Dure L, et al. Treatment approaches for functional neurological disorders in children. Curr Treat Options Neurol. 2022;24(2):77–97. doi: 10.1007/s11940-022-00708-5
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Chudleigh C, Savage B, et al. Evidence-based mind-body interventions for children and adolescents with functional neurological disorder. Harv Rev Psychiatry. 2023;31(2):60–82. doi: 10.1097/HRP.0000000000000358
   PubMed Web of Science ®Google Scholar
• Savage B, Chudleigh C, Hawkes C, et al. Treatment of functional seizures in children and adolescents: a mind-body manual for health professionals: Australian Academic Press; 2022.
   Google Scholar
• Fobian AD, Long DM, Szaflarski JP. Retraining and control therapy for pediatric psychogenic non-epileptic seizures. Ann Clin Transl Neurol. 2020;7(8):1410–1419. doi: 10.1002/acn3.51138
   PubMed Web of Science ®Google Scholar
• Stager L, Morriss S, McKibben L, et al. Sense of control, selective attention and cognitive inhibition in pediatric functional seizures: a prospective case-control study. Seizure. 2022;98:79–86 PubMed. doi: 10.1016/j.seizure.2022.03.021
   PubMed Web of Science ®Google Scholar
• Sawchuk T, Buchhalter J, Senft B. Psychogenic nonepileptic seizures in children-prospective validation of a clinical care pathway & risk factors for treatment outcome. Epilepsy Behav. 2020;105:106971. doi: 10.1016/j.yebeh.2020.106971
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Sawchuk T, Waugh JL, et al. Changing the culture of care for children and adolescents with functional neurological disorder. Epilepsy & Behavior Reports. 2021;16:1004486. doi: 10.1016/j.ebr.2021.100486
   Google Scholar
• Popkirov S. Double vision. Brain. 2023;146(1):2–3. doi: 10.1093/brain/awac409
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Palmer DM, Brown KJ, et al. Reduction of autonomic regulation in children and adolescents with conversion disorders. Psychosom Med. 2015;77(4):356–70. doi: 10.1097/PSY.0000000000000184
   PubMed Web of Science ®Google Scholar
• Chudleigh C, Savage B, Cruz C, et al. Use of respiratory rates and heart rate variability in the assessment and treatment of children and adolescents with functional somatic symptoms. Clin Child Psychol Psychiatry. 2019;24(1):29–39. doi: 10.1177/1359104518807742
   PubMed Web of Science ®Google Scholar
• Sawchuk T, Buchhalter J, Senft B. Psychogenic non-epileptic seizures in children – psychophysiology & dissociative characteristics. Psychiatry Res. 2020;294:113544. doi: 10.1016/j.psychres.2020.113544
   PubMed Web of Science ®Google Scholar
• Paredes-Echeverri S, Maggio J, Begue I, et al. Autonomic, endocrine, and inflammation profiles in functional neurological disorder: a systematic review and meta-analysis. J neuropsych clin neurosci. 2022;34(1):30–43. doi: 10.1176/appi.neuropsych.21010025
   PubMed Web of Science ®Google Scholar
• Kozlowska K. The body comes to family therapy: utilizing research to formulate treatment interventions with somatising children and their families. Aust N Z J Fam Ther. 2016;37:6–29. doi: 10.1002/anzf.1133
   Web of Science ®Google Scholar
• Kozlowska K, Rampersad R, Cruz C, et al. The respiratory control of carbon dioxide in children and adolescents referred for treatment of psychogenic non-epileptic seizures. Eur Child Adolesc Psychiatry. 2017;26(10):1207–1217. doi: 10.1007/s00787-017-0976-0
   PubMed Web of Science ®Google Scholar
• Benarroch EE. Brainstem respiratory chemosensitivity: new insights and clinical implications. Neurology. 2007;68(24):2140–3. doi: 10.1212/01.wnl.0000266560.60371.98
   PubMed Web of Science ®Google Scholar
• Braun M, Sawchuk T, Simpkins A, et al. Quantitative EEG during hyperventilation as a biomarker for pediatric psychogenic non-epileptic seizures (PNES). Poster session presented at the annual meeting of the American Epilepsy Society, Chicago, USA. 2021.
   Google Scholar
• Fleming S, Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet. 2011;377(9770):1011–1018. doi: 10.1016/S0140-6736(10)62226-X
   PubMed Web of Science ®Google Scholar
• Wallis LA, Healy M, Undy MB, et al. Age related reference ranges for respiration rate and heart rate from 4 to 16 years. Arch Dis Child. 2005;90(11):1117–1121. doi: 10.1136/adc.2004.068718
   PubMed Web of Science ®Google Scholar
• Sparing R, Dafotakis M, Buelte D, et al. Excitability of human motor and visual cortex before, during, and after hyperventilation. J Appl Physiol (1985). 2007;102(1):406–411. doi: 10.1152/japplphysiol.00770.2006
   PubMed Web of Science ®Google Scholar
• Jensen O, Hari R, Kaila K. Visually evoked gamma responses in the human brain are enhanced during voluntary hyperventilation. Neuroimage. 2002;15(3):575–586. doi: 10.1006/nimg.2001.1013
   PubMed Web of Science ®Google Scholar
• Carbon M, Wübbeler G, Trahms L, et al. Hyperventilation-induced human cerebral magnetic fields non-invasively monitored by multichannel ‘direct current’ magnetoencephalography. Neurosci Lett. 2000;287:227–230 PubMed. doi: 10.1016/S0304-3940(00)01192-7
   PubMed Web of Science ®Google Scholar
• Stenkamp K, Palva JM, Uusisaari M, et al. Enhanced temporal stability of cholinergic hippocampal gamma oscillations following respiratory alkalosis in vitro. J Neurophysiol. 2001;85(5):2063 PubMed–9. doi: 10.1152/jn.2001.85.5.2063
   Web of Science ®Google Scholar
• Engel GL, Ferris EB, Logan M. Hyperventilation: analysis of clinical symptomatology. Ann Intern Med. 1947;27:683–704 PubMed.
   PubMed Web of Science ®Google Scholar
• Hauge A, Thoresen M, Walloe L. Changes in cerebral blood flow during hyperventilation and CO2-breathing measured transcutaneously in humans by a bidirectional, pulsed, ultrasound doppler blood velocitymeter. Acta Physiol Scand. 1980;110(2):167 PubMed–73. doi: 10.1111/j.1748-1716.1980.tb06647.x
   Google Scholar
• Kraaier V, van Huffelen AC, Wieneke GH. Changes in quantitative EEG and blood flow velocity due to standardized hyperventilation; a model of transient ischaemia in young human subjects. Electroencephalogr Clin Neurophysiol. 1988;70(5):377–387. doi:10.1016/0013-4694(88)90015-6
   PubMedGoogle Scholar
• Gibbs DM. Hyperventilation-induced cerebral ischemia in panic disorder and effect of nimodipine. Am J Psychiatry. 1992;149(11):1589–1591.
   PubMed Web of Science ®Google Scholar
• Rai S, Foster S, Griffiths KR, et al. Altered resting-state neural networks in children and adolescents with functional neurological disorder. NeuroImage Clin. 2022;35:103110.
   PubMed Web of Science ®Google Scholar
• Stager L, Mueller C, Morriss S, et al. Sense of control, selective attention, cognitive inhibition, and psychosocial outcomes after retraining and control therapy (ReACT) in pediatric functional seizures. Epilepsy Behav. 2023;142:109143–. doi: 10.1016/j.yebeh.2023.109143
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Chudleigh C, Cruz C, et al. Psychogenic non-epileptic seizures in children and adolescents: part I – Diagnostic formulations. Clin Child Psychol Psychiatry. 2018;23(1):140–159. doi: 10.1177/1359104517732118
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Chudleigh C, Cruz C, et al. Psychogenic non-epileptic seizures in children and adolescents: part II – explanations to families, treatment, and group outcomes. Clin Child Psychol Psychiatry. 2018;23(1):160–176. doi: 10.1177/1359104517730116
   PubMed Web of Science ®Google Scholar
• Clow A, Hucklebridge F, Thorn L. The cortisol awakening response in context. Int Rev Neurobiol. 2010;93:153–175 PubMed.
   PubMed Web of Science ®Google Scholar
• Baumler D, Kirschbaum C, Kliegel M, et al. The cortisol awakening response in toddlers and young children. Psychoneuroendocrinology. 2013;38(11):2485–2492. doi: 10.1016/j.psyneuen.2013.05.008
   PubMed Web of Science ®Google Scholar
• Platje E, Vermeiren RR, Branje SJ, et al. Long-term stability of the cortisol awakening response over adolescence. Psychoneuroendocrinology. 2013;38(2):271–280. doi: 10.1016/j.psyneuen.2012.06.007
   PubMed Web of Science ®Google Scholar
• Filaire E, Ferreira JP, Oliveira M, et al. Diurnal patterns of salivary alpha-amylase and cortisol secretion in female adolescent tennis players after 16 weeks of training. Psychoneuroendocrinology. 2013;38(7):1122–1132. doi: 10.1016/j.psyneuen.2012.11.001
   PubMed Web of Science ®Google Scholar
• Chung J, Mukerji S, Kozlowska K. Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder. Aust N Z J Psychiatry. 2022;57(1):115–129. doi: 10.1177/00048674221082520
   PubMed Web of Science ®Google Scholar
• Baumeister D, Akhtar R, Ciufolini S, et al. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry. 2016;21(5):642–649. doi: 10.1038/mp.2015.67
   PubMed Web of Science ®Google Scholar
• Jonker I, Rosmalen JGM, Schoevers RA. Childhood life events, immune activation and the development of mood and anxiety disorders: the TRAILS study. Transl Psychiatry. 2017;7(5):e1112. doi: 10.1038/tp.2017.62
   PubMedGoogle Scholar
• Kozlowska K, Chung J, Cruickshank B, et al. Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder. Eur Child Adolesc Psychiatry. 2019;28(4):491–504. doi: 10.1007/s00787-018-1212-2
   PubMed Web of Science ®Google Scholar
• Umesh S, Tikka SK, Goyal N, et al. Aberrant gamma band cortical sources and functional connectivity in adolescents with psychogenic non-epileptic seizures: a preliminary report. Psychiatry Res. 2017;247:51–54. PubMed. doi: 10.1016/j.psychres.2016.11.003
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Spooner CJ, Palmer DM, et al. “Motoring in idle”: the default mode and somatomotor networks are overactive in children and adolescents with functional neurological symptoms. NeuroImage Clin. 2018;18:730–743. PubMed. doi: 10.1016/j.nicl.2018.02.003
   PubMed Web of Science ®Google Scholar
• Vuilleumier P. Brain circuits implicated in psychogenic paralysis in conversion disorders and hypnosis. Neurophysiol Clin. 2014;44(4):323–337. doi: 10.1016/j.neucli.2014.01.003
   PubMed Web of Science ®Google Scholar
• Voon V. Functional neurological disorders: imaging. Neurophysiol Clin. 2014;44(4):339 PubMed–42. doi: 10.1016/j.neucli.2014.07.003
   Web of Science ®Google Scholar
• Perez DL, Nicholson TR, Asadi-Pooya AA, et al. Neuroimaging in functional neurological disorder: state of the field and research agenda. NeuroImage Clin. 2021;30:102623. doi: 10.1016/j.nicl.2021.102623
   PubMed Web of Science ®Google Scholar
• Radmanesh M, Jalili M, Kozlowska K. Activation of functional brain networks in children and adolescents with psychogenic non-epileptic seizures. Front Hum Neurosci. 2020;14:339. doi: 10.3389/fnhum.2020.00339
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Melkonian D, Spooner CJ, et al. Cortical arousal in children and adolescents with functional neurological symptoms during the auditory oddball task. NeuroImage Clin. 2017;13:228–236 PubMed. doi: 10.1016/j.nicl.2016.10.016
   PubMed Web of Science ®Google Scholar
• Madec T, Lagarde S, McGonigal A, et al. Transient cortico-cortical disconnection during psychogenic nonepileptic seizures (PNES). Epilepsia. 2020;61(8): PubMed e101–e106. doi: 10.1111/epi.16623
   Web of Science ®Google Scholar
• Kozlowska K, Griffiths KR, Foster SL, et al. Grey matter abnormalities in children and adolescents with functional neurological symptom disorder. NeuroImage Clin. 2017;15:306–314 PubMed. doi: 10.1016/j.nicl.2017.04.028
   PubMed Web of Science ®Google Scholar
• Charney M, Foster S, Shuklab V, et al. Neurometabolic alterations in children and adolescents with functional neurological disorder NeuroImage clinical. NeuroImage Clin. 2024;41:103557. doi: 10.1016/j.nicl.2023.103557.
   PubMed Web of Science ®Google Scholar
• Zulfarina MS, Syarifah-Noratiqah SB, Nazrun SA, et al. Pharmacological therapy in panic disorder: Current guidelines and novel drugs discovery for treatment-resistant patient. Clin Psychopharmacol Neurosci. 2019;17(2):145–154. doi: 10.9758/cpn.2019.17.2.145
   PubMed Web of Science ®Google Scholar
• Benjamin J, Levine J, Fux M, et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am J Psychiatry. 1995;152(7):1084–1086.
   PubMed Web of Science ®Google Scholar
• Palatnik A, Frolov K, Fux M, et al. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol. 2001;21(3):335–339. doi: 10.1097/00004714-200106000-00014
   PubMed Web of Science ®Google Scholar
• Concerto C, Chiarenza C, Di Francesco A, et al. Neurobiology and applications of inositol in psychiatry: a narrative review. Curr Issues Mol Biol. 2023;45(2):1762–778. doi: 10.3390/cimb45020113
   PubMed Web of Science ®Google Scholar
• Frank MG, Fonken LK, Watkins LR, et al. Microglia: neuroimmunesensors of stress. Semin Cell Dev Biol. 2019;94:176–185 PubMed. doi: 10.1016/j.semcdb.2019.01.001
   PubMed Web of Science ®Google Scholar
• Frank MG, Weber MD, Watkins LR, et al. Stress-induced neuroinflammatory priming: a liability factor in the etiology of psychiatric disorders. Neurobiol Stress. 2016;4:62–70 PubMed. doi: 10.1016/j.ynstr.2015.12.004
   PubMedGoogle Scholar
• Brenhouse HC, Schwarz JM. Immunoadolescence: Neuroimmune development and adolescent behavior. Neurosci Biobehav Rev. 2016;70:288–299. doi: 10.1016/j.neubiorev.2016.05.035
   PubMed Web of Science ®Google Scholar
• Brenhouse HC, Danese A, Grassi-Oliveira R. Neuroimmune impacts of early-life stress on development and psychopathology. Curr Top Behav Neurosci. 2019;43:423–447.
   PubMedGoogle Scholar
• Donnelly CR, Andriessen AS, Chen G, et al. Central nervous system targets: glial cell mechanisms in chronic pain. Neurotherapeutics. 2020;17(3):846–60. 10.1007/s13311-020-00905-7
   PubMed Web of Science ®Google Scholar
• Perez DL, Aybek S, Popkirov S, et al. A review and expert opinion on the neuropsychiatric assessment of motor functional neurological disorders. J Neuropsychiatry Clin Neurosci. 2021;33(1):14–26. doi: 10.1176/appi.neuropsych.19120357
   PubMed Web of Science ®Google Scholar
• Diez I, Larson AG, Nakhate V, et al. Early-life trauma endophenotypes and brain circuit–gene expression relationships in functional neurological (conversion) disorder. Mol Psychiatry. 2020:3817–3828. doi: 10.1038/s41380-020-0665-0. 26 8
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Brown KJ, Palmer DM, et al. Specific biases for identifying facial expression of emotion in children and adolescents with conversion disorders. Psychosom Med. 2013;75(3):272–280. doi: 10.1097/PSY.0b013e318286be43
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Palmer DM, Brown KJ, et al. Conversion disorder in children and adolescents: a disorder of cognitive control. J Neuropsychol. 2015;9(1):87–108. doi: 10.1111/jnp.12037
   PubMed Web of Science ®Google Scholar
• Hilton RA, Tozzi L, Nesamoney S, et al. Transdiagnostic Neurocognitive Dysfunction in Children and adolescents with mental illness. Nat Mental Health. 2024;2(3):299–309. doi: 10.1038/s44220-023-00199-6
   Google Scholar
• Grob A, Little TD, Wanner B. Control judgements across the lifespan. Int J Behavioral Develop. 1999;23(4):833–854. doi: 10.1080/016502599383568
   Web of Science ®Google Scholar
• Hallett M. Volitional control of movement: the physiology of free will. Clin Neurophysiol. 2007;118(6):1179–1192. doi: 10.1016/j.clinph.2007.03.019
   PubMed Web of Science ®Google Scholar
• Edwards MJ, Fotopoulou A, Parees I. Neurobiology of functional (psychogenic) movement disorders. Curr Opin Neurol. 2013;26(4):442–447. doi: 10.1097/WCO.0b013e3283633953
   PubMed Web of Science ®Google Scholar
• Helgeland H, Savage B, Kozlowska K. Hypnosis in the treatment of functional somatic symptoms in children and adolescents. In: Linden JH, De Benedittis G, Sugarman LJ, and Varga K, editors. The Routledge international handbook of clinical hypnosis: Routledge Taylor & Francis; 2024. p. 515–536.
   Google Scholar
• Gianaros PJ, Wager TD. Brain-body pathways linking psychological stress and physical health. Curr Dir Psychol Sci. 2015;24(4):313–321. doi: 10.1177/0963721415581476
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Schollar-Root O, Savage B, et al. Illness-promoting psychological processes in children and adolescents with functional neurological disorder. Children (Basel). 2023;10(11):1724. doi: 10.3390/children10111724
   PubMed Web of Science ®Google Scholar
• Hansen AS, Rask CU, Christensen AE, et al. Psychiatric disorders in children and adolescents with psychogenic nonepileptic seizures. Neurology. 2021;97(5):e464–e75. doi: 10.1212/WNL.0000000000012270
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Scher S, Williams LM. Patterns of emotional-cognitive functioning in pediatric conversion patients: implications for the conceptualization of conversion disorders. Psychosom Med. 2011;73(9):775–788. doi: 10.1097/PSY.0b013e3182361e12
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Cruz C, Davies F, et al. The utility (or not) of self-report instruments in family assessment for child and adolescent conversion disorders? ANZ J Of Family Therapy. 2016;37:480–499. doi: 10.1002/anzf.1187
   Web of Science ®Google Scholar
• Stager L, Morriss S, Szaflarski JP, et al. Psychiatric and personality factors in pediatric functional seizures: a prospective case-control study. Seizure. 2022;98:105–112 PubMed. doi: 10.1016/j.seizure.2022.04.006
   PubMed Web of Science ®Google Scholar
• Kozlowska K, Gray N, Scher S, et al. Psychologically informed physiotherapy as part of a multidisciplinary rehabilitation program for children and adolescents with functional neurological disorder: physical and mental health outcomes. J Paediatr Child Health. 2021;57(1):73–79. doi: 10.1111/jpc.15122
   PubMed Web of Science ®Google Scholar
• Breukelaar IA, Erlinger M, Harris A, et al. Investigating the neural basis of cognitive control dysfunction in mood disorders. Bipolar Disord. 2020;22(3):286–295. doi: 10.1111/bdi.12844
   PubMed Web of Science ®Google Scholar
• Bryant RA, Andrew E, Korgaonkar MS. Distinct neural mechanisms of emotional processing in prolonged grief disorder. Psychol Med. 2021;51(4):587–595. doi: 10.1017/S0033291719003507
   PubMed Web of Science ®Google Scholar
• Korgaonkar MS, Tran J, Felmingham KL, et al. Neural correlates of emotional processing in panic disorder. NeuroImage Clin. 2021;32:102902. doi: 10.1016/j.nicl.2021.102902
   PubMed Web of Science ®Google Scholar
• Breukelaar IA, Bryant RA, Korgaonkar MS. The functional connectome in posttraumatic stress disorder. Neurobiol Stress. 2021;14:100321. doi: 10.1016/j.ynstr.2021.100321
   PubMed Web of Science ®Google Scholar
• Scott JG, Mihalopoulos C, Erskine HE, et al. Childhood mental and developmental disorders. In: Patel V, Chisholm D, Dua T, Laxminarayan R, Medina-Mora M, editors. Disease control priorities, third edition: volume 4 mental, neurological, and substance use disorders: Washington (DC): World Bank; 2016.
   Google Scholar
• World_Health_Organization. Mental health of adolescents. 2021. cited 2023 Feb 25. Available from: https://www.who.int/news-room/fact-sheets/detail/adolescent-mental-health.
   Google Scholar
• Schlack R, Peerenboom N, Neuperdt L, et al. The effects of mental health problems in childhood and adolescence in young adults: results of the KiGGS cohort. J Health Monit. 2021;6(4):3–19. doi: 10.25646/8863
   PubMedGoogle Scholar
• Yadav A, Agarwal R, Park J. Outcome of psychogenic nonepileptic seizures (PNES) in children: a 2-year follow-up study. Epilepsy Behav. 2015;53:168–173 PubMed. doi: 10.1016/j.yebeh.2015.10.017
   PubMed Web of Science ®Google Scholar
• Sawchuk T, Buchhalter J. Psychogenic nonepileptic seizures in children – psychological presentation, treatment, and short-term outcomes. Epilepsy Behav. 2015;52(Pt A):49–56. doi: 10.1016/j.yebeh.2015.08.032
   PubMedGoogle Scholar
• Paldino MJ, Chu ZD, Chapieski ML, et al. Repeatability of graph theoretical metrics derived from resting-state functional networks in paediatric epilepsy patients. Br J Radiol. 2017;90(1074):20160656 PubMed. doi: 10.1259/bjr.20160656
   PubMed Web of Science ®Google Scholar
• Vaessen MJ, Braakman HM, Heerink JS, et al. Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy. Cereb Cortex. 2013;23(8):1997–2006. PubMed. doi: 10.1093/cercor/bhs186
   PubMed Web of Science ®Google Scholar
• Liampas A, Markoula S, Zis P, et al. Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosis. Acta Epileptologica. 2021;3(1):1–11. doi: 10.1186/s42494-021-00057-x
   Google Scholar
• Reilly C, Jette N, Johnson EC, et al. Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: a report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy. Epilepsia. 2023;64(12):3160–3195. doi: 10.1111/epi.17768
   PubMed Web of Science ®Google Scholar
• Bowlby J. Attachment and loss: volume II: separation, anxiety and anger. London: Hogarth Press and Institute of Psycho-Analysis, 1973.
   Google Scholar
• Bowlby J. Developmental psychiatry comes of age. Am J Psychiatry. 1988;145(1):1–10.
   PubMed Web of Science ®Google Scholar
• Sroufe LA, Coffino B, Carlson EA. Conceptualizing the role of early experience: lessons from the Minnesota longitudinal study. Dev Rev. 2010;30(1):36–51. doi: 10.1016/j.dr.2009.12.002
   PubMed Web of Science ®Google Scholar
• Marmot M, Allen J, Bell R, et al. WHO European review of social determinants of health and the health divide. Lancet. 2012;380(9846):1011–1029.doi: 10.1016/S0140-6736(12)61228-8
   PubMed Web of Science ®Google Scholar
• Rask CU, Ornbol E, Olsen EM, et al. Infant behaviors are predictive of functional somatic symptoms at ages 5–7 years: results from the Copenhagen child cohort CCC2000. J Pediatr. 2013;162:335–342 PubMed. doi: 10.1016/j.jpeds.2012.08.001
   PubMed Web of Science ®Google Scholar
• Crittenden PM. Danger and development: the organization of self-protective strategies. Monographs Society Res Child. 1999;64(3):145–171. 10.1111/1540-5834.00037
   PubMed Web of Science ®Google Scholar
• Farnfield S, Hautamaki A, Nørbech P, et al. DMM assessments of attachment and adaptation: procedures, validity and utility. Clin Child Psychol Psychiatry. 2010;15(3):313–328. doi: 10.1177/1359104510364315
   PubMedGoogle Scholar
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: dSM-5. 4th ed. Arlington (VA): American Psychiatric Association; 2013.
   Google Scholar
• Verrotti A, Agostinelli S, Mohn A, et al. Clinical features of psychogenic non-epileptic seizures in prepubertal and pubertal patients with idiopathic epilepsy. Neurol Sci. 2009;30(4):319–323. doi: 10.1007/s10072-009-0107-x
   PubMed Web of Science ®Google Scholar
• Yang T, Roberts C, Winton-Brown T, et al. Childhood trauma in patients with epileptic vs nonepileptic seizures. Epilepsia. 2022.
   Google Scholar
• Yong K, Chin RFM, Shetty J, et al. Functional neurological disorder in children and young people: incidence, clinical features, and prognosis. Dev Med Child Neurol. 2023;65(9):1238–1246. doi: 10.1111/dmcn.15538
   PubMed Web of Science ®Google Scholar
• Yeom JS, Bernard H, Koh S. Gender differences in risk factors and psychosocial functioning in children with psychogenic nonepileptic seizures. Epilepsy Behav. 2022;136:108884. doi: 10.1016/j.yebeh.2022.108884
   PubMed Web of Science ®Google Scholar
• Lim N, Wood N, Prasad A, et al. COVID-19 vaccination in Young People with functional neurological disorder: a case-control study. Vaccines (Basel). 2022;10(12):2031. doi: 10.3390/vaccines10122031
   PubMed Web of Science ®Google Scholar
• Rask CU, Bonvanie IJ, Garralda EM. Risk and protective factors and course of functional somatic symptoms in young people. In: Hodes M, Gau SS-F, De Vries PJ, editors. Understanding uniqueness and diversity in child and adolescent mental health: Academic Press; 2018. p. 77–113.
   Google Scholar
• Begue I, Nicholson TR, Kozlowska K, et al. Psychiatry’s modern role in functional neurological disorder: join the renaissance. Psychol Med. 2021:1–3. doi: 10.1017/S0033291721002038
   Web of Science ®Google Scholar
• Duarte FV, Palmeira CM, Rolo AP. The role of microRnas in Mitochondria: small players acting wide. Genes (Basel). 2014;5(4):865–886. doi: 10.3390/genes5040865
   PubMed Web of Science ®Google Scholar