Background: First-episode schizophrenia (FE-SZ) and attention deficit hyperactivity disorder (ADHD) are both neuropsychiatric disorders associated with an impaired dopaminergic transmission. Though displaying different clinical phenotypes, a common pathophysiological pathway is discussed controversially. Several studies using transcranial magnetic stimulation (TMS) revealed abnormalities in human motor cortex excitability in both schizophrenia and ADHD patients. Studies on cortical excitability comparing these two diseases directly are lacking. Method: In this study, a total of 94 subjects were analyzed. Twenty-five FE-SZ patients were directly compared with 28 ADHD patients and 41 healthy controls (HC). We investigated cortical excitability (inhibitory and facilitatory networks) with single- and paired-pulse TMS to the left and right motor cortex. Results: Compared to HC, FE-SZ/ADHD patients displayed an impaired cortical inhibition over the left hemisphere. Apart from an enhanced intracortical facilitation, FE-SZ patients did not differ compared to ADHD patients in the main outcome measures. Both patient groups presented a dysfunctional hemispheric pattern of cortical inhibition and facilitation in comparison with HC. Conclusion: The results of this study indicate a pattern of cortical disinhibition and abnormal hemispheric balance of intracortical excitability networks in two different psychiatric diseases. These effects might be associated with an imbalance in GABAergic and dopaminergic transmission and might provide evidence for a common pathophysiological pathway of both diseases.

Ross RG, Olincy A, Harris JG, Sullivan B, Radant A: Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults with schizophrenia, ADHD, and a normal comparison group. Biol Psychiatry 2000;48:197–203.
Marsh PJ, Williams LM: ADHD and schizophrenia phenomenology: visual scanpaths to emotional faces as a potential psychophysiological marker? Neurosci Biobehav Rev 2006;30:651–665.
Pani L: Clinical implications of dopamine research in schizophrenia. Curr Med Res Opin 2002;18(suppl 3):s3–s7.
Solanto MV: Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res 2002;130:65–71.
Ohno M: The dopaminergic system in attention deficit/hyperactivity disorder. Congenit Anom (Kyoto) 2003;43:114–122.
Durston S: A review of the biological bases of ADHD: what have we learned from imaging studies? Ment Retard Dev Disabil Res Rev 2003;9:184–195.
Carriere P, Bonhomme D, Lemperiere T: Amisulpride has a superior benefit/risk profile to haloperidol in schizophrenia: results of a multicentre, double-blind study (the amisulpride study group). Eur Psychiatry 2000;15:321–329.
Jucaite A, Fernell E, Halldin C, Forssberg H, Farde L: Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity. Biol Psychiatry 2005;57:229–238.
Pouget P, Wattiez N, Rivaud-Pechoux S, Gaymard B: A fragile balance: perturbation of GABA mediated circuit in prefrontal cortex generates high intraindividual performance variability. PLoS One 2009;4:e5208.
Hashimoto T, Bazmi HH, Mirnics K, Wu Q, Sampson AR, Lewis DA: Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia. Am J Psychiatry 2008;165:479–489.
Wobrock T, Schneider M, Kadovic D, Schneider-Axmann T, Ecker UK, Retz W, Rosler M, Falkai P: Reduced cortical inhibition in first-episode schizophrenia. Schizophr Res 2008;105:252–261.
Richter MM, Ehlis AC, Jacob CP, Fallgatter AJ: Cortical excitability in adult patients with attention-deficit/hyperactivity disorder (ADHD). Neurosci Lett 2007;419:137–141.
Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD: Corticocortical inhibition in human motor cortex. J Physiol 1993;471:501–519.
Ziemann U: TMS and drugs. Clin Neurophysiol 2004;115:1717–1729.
Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J: Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol 1999;517(Pt 2):591–597.
Siebner HR, Dressnandt J, Auer C, Conrad B: Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 1998;21:1209–1212.
Pascual-Leone A, Manoach DS, Birnbaum R, Goff DC: Motor cortical excitability in schizophrenia. Biol Psychiatry 2002;52:24–31.
Eichhammer P, Wiegand R, Kharraz A, Langguth B, Binder H, Hajak G: Cortical excitability in neuroleptic-naive first-episode schizophrenic patients. Schizophr Res 2004;67:253–259.
Daskalakis ZJ, Christensen BK, Chen R, Fitzgerald PB, Zipursky RB, Kapur S: Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation. Arch Gen Psychiatry 2002;59:347–354.
Fitzgerald PB, Brown TL, Daskalakis ZJ, Kulkarni J: A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia. Psychiatry Res 2002;114:11–22.
Wobrock T, Schneider-Axmann T, Retz W, Rosler M, Kadovic D, Falkai P, Schneider M: Motor circuit abnormalities in first-episode schizophrenia assessed with transcranial magnetic stimulation. Pharmacopsychiatry 2009;42:194–201.
Moll GH, Heinrich H, Trott G, Wirth S, Rothenberger A: Deficient intracortical inhibition in drug-naive children with attention-deficit hyperactivity disorder is enhanced by methylphenidate. Neurosci Lett 2000;284:121–125.
Buchmann J, Gierow W, Weber S, Hoeppner J, Klauer T, Benecke R, Haessler F, Wolters A: Restoration of disturbed intracortical motor inhibition and facilitation in attention deficit hyperactivity disorder children by methylphenidate. Biol Psychiatry 2007;62:963–969.
Gilbert DL, Bansal AS, Sethuraman G, Sallee FR, Zhang J, Lipps T, Wassermann EM: Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov Disord 2004;19:416–425.
Schneider M, Retz W, Freitag C, Irsch J, Graf P, Retz-Junginger P, Rosler M: Impaired cortical inhibition in adult ADHD patients: a study with transcranial magnetic stimulation. J Neural Transm Suppl 2007:303–309.
Hoeppner J, Neumeyer M, Wandschneider R, Herpertz SC, Gierow W, Haessler F, Buchmann J: Intracortical motor inhibition and facilitation in adults with attention deficit/hyperactivity disorder. J Neural Transm 2008;115:1701–1707.
Hoeppner J, Wandschneider R, Neumeyer M, Gierow W, Haessler F, Herpertz SC, Buchmann J: Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate. J Neural Transm 2008;115:777–785.
Annett M: A classification of hand preference by association analysis. Br J Psychol 1970;61:303–321.
Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M: Strukturiertes klinisches Interview für DSM-IV; in Spitzer RL, Williams JB, Gibbon M, First MB (eds): Achse I: Psychische Störungen. A German, Advanced Adaptation of the Original SCID Version. Göttingen, Hogrefe, 1997.
National Institute of Mental Health: CGI: Clinical Global Impressions; in Guy W, Bonato RR (eds): Manual for the ECDEU Assessment Battery. Chevy Chase, National Institute of Mental Health, 1976.
Endicott J, Spitzer RL, Fleiss JL, Cohen J: The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976;33:766–771.
Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.
Woods SW: Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003;64:663–667.
Rösler M, Retz W, Retz-Junginger P, Thome J, Supprian T, Nissen T, Stieglitz RD, Blocher D, Hengesch G, Trott GE: Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist. Nervenarzt 2004;75:888–895.
Wender PH, Wolf LE, Wasserstein J: Adults with ADHD. An overview. Ann NY Acad Sci 2001;931:1–16.
Daskalakis ZJ, Christensen BK, Chen R, Fitzgerald PB, Zipursky RB, Kapur S: Effect of antipsychotics on cortical inhibition using transcranial magnetic stimulation. Psychopharmacology (Berl) 2003;170:255–262.
Liu SK, Fitzgerald PB, Daigle M, Chen R, Daskalakis ZJ: The relationship between cortical inhibition, antipsychotic treatment, and the symptoms of schizophrenia. Biol Psychiatry 2009;65:503–509.
Hasan A, Nitsche MA, Rein B, Schneider-Axmann T, Guse B, Gruber O, Falkai P, Wobrock T: Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav Brain Res 2011;224:15–22.
Bajbouj M, Gallinat J, Niehaus L, Lang UE, Roricht S, Meyer BU: Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia. Pharmacopsychiatry 2004;37:74–80.
Hasan A, Nitsche MA, Herrmann M, Schneider-Axmann T, Marshall L, Gruber O, Falkai P, Wobrock T: Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study. Brain Stimul 2012;5:475–483.
McDonnell MN, Orekhov Y, Ziemann U: The role of GABA(b) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 2006;173:86–93.
Ni Z, Gunraj C, Chen R: Short interval intracortical inhibition and facilitation during the silent period in human. J Physiol 2007;583:971–982.
Hale TS, Smalley SL, Walshaw PD, Hanada G, Macion J, McCracken JT, McGough JJ, Loo SK: Atypical EEG beta asymmetry in adults with ADHD. Neuropsychologia 2010;48:3532–3539.
White T, Nelson M, Lim KO: Diffusion tensor imaging in psychiatric disorders. Top Magn Reson Imaging 2008;19:97–109.
Shapleske J, Rossell SL, Woodruff PW, David AS: The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance. Brain Res Brain Res Rev 1999;29:26–49.
Schmitt A, Hasan A, Gruber O, Falkai P: Schizophrenia as a disorder of disconnectivity. Eur Arch Psychiatry Clin Neurosci 2011;261(Suppl 2):S150–S154.
Fitzgerald PB, Brown TL, Daskalakis ZJ: The application of transcranial magnetic stimulation in psychiatry and neurosciences research. Acta Psychiatr Scand 2002;105:324–340.
Suppa A, Ortu E, Zafar N, Deriu F, Paulus W, Berardelli A, Rothwell JC: Theta burst stimulation induces after-effects on contralateral primary motor cortex excitability in humans. J Physiol 2008;586:4489–4500.
Wassermann EM, Wedegaertner FR, Ziemann U, George MS, Chen R: Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. Neurosci Lett 1998;250:141–144.
Heide G, Witte OW, Ziemann U: Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation. Exp Brain Res 2006;171:26–34.
Cantello R, Tarletti R, Civardi C: Transcranial magnetic stimulation and Parkinson’s disease. Brain Res Brain Res Rev 2002;38:309–327.
Beauregard M, Ferron A: Dopamine modulates the inhibition induced by GABA in rat cerebral cortex: an iontophoretic study. Eur J Pharmacol 1991;205:225–231.
Schneider M, Retz W, Rösler M: Effects of long-acting methylphenidate in adults with attention deficit hyperactivity disorder: a study with paired-pulse transcranial magnetic stimulation. Neuropsychobiology 2011; 64:195–201.
Moll GH, Heinrich H, Trott GE, Wirth S, Bock N, Rothenberger A: Children with comorbid attention-deficit-hyperactivity disorder and tic disorder: evidence for additive inhibitory deficits within the motor system. Ann Neurol 2001;49:393–396.
Nitsche MA, Monte-Silva K, Kuo MF, Paulus W: Dopaminergic impact on cortical excitability in humans. Rev Neurosci 2010;21:289–298.
Bajbouj M, Lisanby SH, Lang UE, Danker-Hopfe H, Heuser I, Neu P: Evidence for impaired cortical inhibition in patients with unipolar major depression. Biol Psychiatry 2006;59:395–400.
Greenberg BD, Ziemann U, Cora-Locatelli G, Harmon A, Murphy DL, Keel JC, Wassermann EM: Altered cortical excitability in obsessive-compulsive disorder. Neurology 2000;54:142–147.
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