Skip to main content Accessibility help
×
Home

Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood

  • S. Dalsgaard (a1) (a2) (a3) (a4), P.B. Mortensen (a1) (a4), M. Frydenberg (a5), C.M. Maibing (a6), M. Nordentoft (a4) (a6) and P.H. Thomsen (a2)...

Abstract

Purpose:

To estimate the risk of schizophrenia in adulthood among children and adolescents with ADHD compared to the background population.

Subjects/materials and methods:

Two hundred and eight youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of schizophrenia were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of schizophrenia for cases with ADHD, compared to the normal population, was calculated as risk ratios. Hazard ratios (HR's) by Cox regression were calculated in the predictor analyses.

Results:

Mean age for ADHD cases at follow-up was 31.1 years. Schizophrenia diagnoses were given to 3.8% of these cases. Compared to the general population, RR of schizophrenia in cases with ADHD was 4.3 (95% CI 1.9–8.57).

Discussion and conclusion:

This prospective follow-up study found children with ADHD to be at higher risk of later schizophrenia than controls. If replicated, these results warrant increased focus on the possible emergence symptoms of schizophrenia or schizophreniform psychosis during clinical follow-up of patients with ADHD.

Copyright

Corresponding author

*Corresponding author. National Centre for Register-based Research, Department of Economics and Business, School of Business and Social Sciences, Aarhus University, Fuglesangs Allé 4, Building K, 8210 Aarhus V, Denmark. Tel.: +45 24 41 37 87. E-mail address: sdalsgaard@ncrr.dk (S. Dalsgaard).

References

Hide All
[1]Abel, K.M., Wicks, S., Susser, E.S., Dalman, C., Pedersen, M.G., Mortensen, P.B.et al.Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? Arch Gen Psychiatry 2010;67:923930.
[2]American Psychiatric Association, Diagnostic and statistical manual of mental disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
[3]Biederman, J., Faraone, S., Milberger, S., Curtis, S., Chen, L., Marrs, A.et al.Predictors of persistence and remission of ADHD into adolescence: results from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 1996;35:343351.
[4]Biederman, J., Faraone, S., Milberger, S., Guite, J., Mick, E., Chen, L.et al.A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry 1996;53:437446.
[5]Biederman, J., Monuteaux, M.C., Mick, E., Spencer, T., Wilens, T.E., Silva, J.M.et al.Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study. Psychol Med 2006;36:167179.
[6]BootsMiller, B.J., Ribisl, K.M., Mowbray, C.T., Davidson, W.S., Walton, M.A., Herman, S.E.Methods of ensuring high follow-up rates: lessons from a longitudinal study of dual diagnosed participants. Subst Use Misuse 1998;33:26652685.
[7]Carpenter, M.D., Winsberg, B.G., Camus, L.A.Methylphenidate augmentation therapy in schizophrenia. J Clin Psychopharmacol 1992;12:273275.
[8]Cherland, E., Fitzpatrick, R.Psychotic side effects of psychostimulants: a 5-year review. Can J Psychiatry 1999;44:811813.
[9]Crow, T.J., Done, D.J., Sacker, A.Childhood precursors of psychosis as clues to its evolutionary origins. Eur Arch Psychiatry Clin Neurosci 1995;245:6169.
[10]Dalsgaard, S., Hansen, N., Mortensen, P.B., Damm, D., Thomsen, P.H.Reassessment of ADHD in a historical cohort of children treated with stimulants in the period 1969–1989. Eur Child Adolesc Psychiatry 2001;10:230239.
[11]Dalsgaard, S., Mortensen, P.B., Frydenberg, M., Thomsen, P.H.Conduct problems, gender and adult psychiatric outcome of children with attention-deficit hyperactivity disorder. Br J Psychiatry 2002;181:416421.
[12]Dalsgaard, S., Mortensen, P.B., Frydenberg, M., Thomsen, P.H.Long-term criminal outcome of children with attention deficit hyperactivity disorder. Crim Behav Ment Health 2013;23:8698.
[13]Dalsgaard, S., Nielsen, H.S., Simonsen, M.Five-fold increase in national prevalence rates of ADHD medications for children and adolescents with Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder and other psychiatric disorders–A Danish register-based study. J Child Adolesc Psychopharmacol 2013;23:432438.
[14]Davidson, M., Reichenberg, A., Rabinowitz, J., Weiser, M., Kaplan, Z., Mark, M.Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 1999;156:13281335.
[15]de la Serna, E., Baeza, I., Toro, J., Andres, S., Puig, O., Sanchez-Guistau, V.et al.Relationship between clinical and neuropsychological characteristics in child and adolescent first degree relatives of subjects with schizophrenia. Schizophr Res 2010;116:159167.
[16]Dichter, G.S., Damiano, C.A., Allen, J.A.Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. J Neurodev Dis 2012;4:19.
[17]Ekinci, O., Sabuncuoglu, O.Psychosis associated with switching from risperidone to aripiprazole in an adolescent on methylphenidate treatment. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:648649.
[18]Faraone, S.V., Biederman, J., Mennin, D., Gershon, J., Tsuang, M.T.A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome. J Am Acad Child Adolesc Psychiatry 1996;35:14491459.
[19]Fischer, M., Barkley, R.A., Fletcher, K.E., Smallish, L.The adolescent outcome of hyperactive children: predictors of psychiatric, academic, social, and emotional adjustment. J Am Acad Child Adolesc Psychiatry 1993;32:324332.
[20]Galynker, I., Ieronimo, C., Miner, C., Rosenblum, J., Vilkas, N., Rosenthal, R.Methylphenidate treatment of negative symptoms in patients with dementia. J Neuropsychiatry Clin Neurosci 1997;9:231239.
[21]Gelperin, K., Phelan, K.Psychiatric adverse events associated with drug treatment of ADHD: review of postmarketing safety data. FDA Report PID D050243. US Food and Drug Administration; 2006 [Last accessed March 26th 2013]http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_11_01_AdverseEvents.pdf.
[22]Gerlach, J., Bjorndal, N., Christensson, E.Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia. Psychopharmacology (Berl) 1984;82:131134.
[23]Gershon, J.A meta-analytic review of gender differences in ADHD. J Atten Disord 2002;5:143154.
[24]Greiner, C., Enss, E., Haen, E.[Drug-induced psychosis after intake of a modified–release formulation of methylphenidate]. Psychiatr Prax 2009;36:8991.
[25]Hasson, R., Fine, J.G.Gender differences among children with ADHD on continuous performance tests: a meta-analytic review. J Atten Disord 2012;16:190198.
[26]Hechtman, L.Predictors of long-term outcome in children with attention-deficit/hyperactivity disorder. Pediatr Clin North Am 1999;46:10391052.
[27]Hellgren, L., Gillberg, I.C., Bagenholm, A., Gillberg, C.Children with deficits in attention, motor control and perception (DAMP) almost grown up: psychiatric and personality disorders at age 16 years. J Child Psychol Psychiatry 1994;35:12551271.
[28]Helzer, J.E.Standardized interviews in psychiatry. Psychiatr Dev 1983;1:161178.
[29]Hurtig, T.M., Taanila, A., Veijola, J., Ebeling, H., Maki, P., Miettunen, J.et al.Associations between psychotic-like symptoms and inattention/hyperactivity symptoms. Soc Psychiatry Psychiatr Epidemiol 2011;46:1727.
[30]IBM Corp.. IBM SPSS Statistics version 19.0.0. Armonk, NY: IBM Corp.; 2010.
[31]Janowsky, D.S., Davis, J.M.Dopamine, psychomotor stimulants, and schizophrenia: effects of methylphenidate and the stereoisomers of amphetamine in schizophrenics. Adv Biochem Psychopharmacol 1974;12:317323.
[32]Janowsky, D.S., Davis, J.M.Methylphenidate, dextroamphetamine, and levamfetamine. Effects on schizophrenic symptoms. Arch Gen Psychiatry 1976;33:304308.
[33]Janowsky, D.S., Huey, L., Storms, L., Judd, L.L.Methylphenidate hydrochloride effects on psychological tests in acute schizophrenic and nonpsychotic patients. Arch Gen Psychiatry 1977;34:189194.
[34]Jody, D., Lieberman, J.A., Geisler, S., Szymanski, S., Alvir, J.M.Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia. Psychopharmacol Bull 1990;26:224230.
[35]Kim-Cohen, J., Caspi, A., Moffitt, T.E., Harrington, H., Milne, B.J., Poulton, R.Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort. Arch Gen Psychiatry 2003;60:709717.
[36]Koreen, A.R., Lieberman, J.A., Alvir, J., Chakos, M.The behavioral effect of m-chlorophenylpiperazine (mCPP) and methylphenidate in first-episode schizophrenia and normal controls. Neuropsychopharmacology 1997;16:6168.
[37]Kraemer, M., Uekermann, J., Wiltfang, J., Kis, B.Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature. Clin Neuropharmacol 2010;33:204206.
[38]Levy, F., Hay, D.A., Bennett, K.S., McStephen, M.Gender differences in ADHD subtype comorbidity. J Am Acad Child Adolesc Psychiatry 2005;44:368376.
[39]Lieberman, J.A., Alvir, J., Geisler, S., Ramos-Lorenzi, J., Woerner, M., Novacenko, H.et al.Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia. Neuropsychopharmacology 1994;11:107118.
[40]Lieberman, J.A., Kane, J.M., Alvir, J.Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 1987;91:415433.
[41]Linnet, K.M., Dalsgaard, S., Obel, C., Wisborg, K., Henriksen, T.B., Rodriguez, A.et al.Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence. Am J Psychiatry 2003;160:10281040.
[42]Loeber, R.Initiation, escalation and desistance in juvenile offending and their correlates. J Crim Law Criminol (1931) 1991;82:3682.
[43]Lucas, A.R., Weiss, M.Methylphenidate hallucinosis. JAMA 1971;217:10791081.
[44]Lysaker, P.H., Vohs, J.L., Tsai, J.Negative symptoms and concordant impairments in attention in schizophrenia: associations with social functioning, hope, self-esteem and internalized stigma. Schizophr Res 2009;110:165172.
[45]Mannuzza, S., Klein, R.G., Bessler, A., Malloy, P., LaPadula, M.Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry 1993;50:565576.
[46]Mannuzza, S., Klein, R.G., Bessler, A., Malloy, P., LaPadula, M.Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 1998;155:493498.
[47]Mannuzza, S., Klein, R.G., Bonagura, N., Malloy, P., Giampino, T.L., Addalli, K.A.Hyperactive boys almost grown up. V. Replication of psychiatric status. Arch Gen Psychiatry 1991;48:7783.
[48]Mannuzza, S., Klein, R.G., Konig, P.H., Giampino, T.L.Hyperactive boys almost grown up. IV. Criminality and its relationship to psychiatric status. Arch Gen Psychiatry 1989;46:10731079.
[49]Mannuzza, S., Klein, R.G., Moulton, J.L.Lifetime criminality among boys with attention deficit hyperactivity disorder: a prospective follow-up study into adulthood using official arrest records. Psychiatry Res 2008;160:237246.
[50]Milberger, S., Biederman, J., Faraone, S.V., Wilens, T., Chu, M.P.Associations between ADHD and psychoactive substance use disorders. Findings from a longitudinal study of high-risk siblings of ADHD children. Am J Addict 1997;6:318329.
[51]Mosholder, A.Psychiatric adverse events in clinical trials of drugs for ADHD. FDA Report PID D060163 US Food and Drug Administration; 2006 [Last accessed March 26th 2013]http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_10_01_Mosholder.pdf.
[52]Niemi, L.T., Suvisaari, J.M., Tuulio-Henriksson, A., Lönnqvist, J.K.Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophr Res 2003;60:239258.
[53]Owen, M.J., O’Donovan, M.C., Thapar, A., Craddock, N.Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 2011;198:173175.
[54]Pedersen, C.B., Gøtzsche, H., Møller, J.Ø., Mortensen, P.B.The Danish Civil Registration System – A cohort of eight million persons. Dan Med Bull 2006;53:441449.
[55]Phelan, K.One year post-pediatric exclusivity postmarketing adverse event review: Adderall XR. FDA Report PID D040761 US Food and Drug Administration; 2006 [Last accessed March 26th 2013]http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_05_02_AdderallSafetyReview.pdf.
[56]Phelan, K.Summary of psychiatric and neurological adverse events from June 2005 1-year post pediatric exclusivity reviews of Concerta and other methylphenidate products. US Food and Drug Administration; 2006 [Last accessed March 26th 2013]http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_09_01_Methsummary.pdf.
[57]Ross, R.G.Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder. Am J Psychiatry 2006;163:11491152.
[58]Rubino, I.A., Frank, E., Croce Nanni, R., Pozzi, D., Lanza di Scalea, T., Siracusano, A.A comparative study of axis I antecedents before age 18 of unipolar depression, bipolar disorder and schizophrenia. Psychopathology 2009;42:325332.
[59]Rucklidge, J.J.Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 2010;33:357373.
[60]Satterfield, J., Swanson, J., Schell, A., Lee, F.Prediction of antisocial behavior in attention-deficit hyperactivity disorder boys from aggression/defiance scores. J Am Acad Child Adolesc Psychiatry 1994;33:185190.
[61]Satterfield, J.H., Faller, K.J., Crinella, F.M., Schell, A.M., Swanson, J.M., Homer, L.D.A 30-year prospective follow-up study of hyperactive boys with conduct problems: adult criminality. J Am Acad Child Adolesc Psychiatry 2007;46:601610.
[62]Schmidt, K., Freidson, S.Atypical outcome in attention deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1990;29:566570.
[63]Sharma, R.P., Javaid, J.I., Pandey, G.N., Janicak, P.G., Davis, J.M.Behavioral and biochemical effects of methylphenidate in schizophrenic and nonschizophrenic patients. Biol Psychiatry 1991;30:459466.
[64]Shen, L.H., Liao, M.H., Tseng, Y.C.Recent advances in imaging of dopaminergic neurons for evaluation of neuropsychiatric disorders. J Biomed Biotechnol 2012;2012:259349.
[65]Sourander, A., Elonheimo, H., Niemela, S., Nuutila, A.M., Helenius, H., Sillanmaki, L.et al.Childhood predictors of male criminality: a prospective population-based follow-up study from age 8 to late adolescence. J Am Acad Child Adolesc Psychiatry 2006;45:578586.
[66]Szeszko, P.R., Bilder, R.M., Dunlop, J.A., Walder, D.J., Lieberman, J.A.Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases. Biol Psychiatry 1999;45:680686.
[67]Uggerby, P., Ostergaard, S.D., Roge, R., Correll, C.U., Nielsen, J.The validity of the schizophrenia diagnosis in the Danish Psychiatric Central Research Register is good. Dan Med J 2013;60:A4578.
[68]Weiss, G., Hechtman, L., Milroy, T., Perlman, T.Psychiatric status of hyperactives as adults: a controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry 1985;24:211220.
[69]World Health Organization. International classification of diseases: manual of the international statistical classification of diseases, injuries and causes of death (ICD-8). Geneva: WHO; 1967.
[70]World Health Organization. The ICD-10 Classification of mental and behavioural disorders: diagnostic criteria for research. Geneva, Switzerland: World Health Organization; 1993.

Keywords

Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood

  • S. Dalsgaard (a1) (a2) (a3) (a4), P.B. Mortensen (a1) (a4), M. Frydenberg (a5), C.M. Maibing (a6), M. Nordentoft (a4) (a6) and P.H. Thomsen (a2)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood

  • S. Dalsgaard (a1) (a2) (a3) (a4), P.B. Mortensen (a1) (a4), M. Frydenberg (a5), C.M. Maibing (a6), M. Nordentoft (a4) (a6) and P.H. Thomsen (a2)...
Submit a response

Comments

No Comments have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *