Locomotor Movement-Pattern Analysis as an Individualized Objective and Quantitative Approach in Psychiatry and Psychopharmacology: Clinical and Theoretical Implications

  • Svetlozar Haralanov
  • Evelina Haralanova
  • Emil Milushev
  • Diana Shkodrova


Psychiatry is the only medical specialty lacking clinically applicable biomarkers for objective quantification of the existing pathology and the subsequent treatment effects at a single-subject level. Based on an original (internationally patented) method for evaluating movement patterns, we have introduced in the everyday clinical practice an easy-to-perform objective and quantitative approach to the individual motor behavior in psychiatric and neurological patients. It involves equilibriometric quantification of the head and body movements during the execution of specific locomotor tasks. For the last 20 years, we have gradually collected a large database from cross-sectional and longitudinal investigations of more than 1000 patients and healthy controls. Comparative analyses have revealed trans-diagnostic similarities among different psychiatric and neurological categories as well as significant within-diagnostic dissimilarities, which can help to separate out subgroups within the same nosological category. Pharmacological challenges and treatment effects permit objective quantification of the normalizing or denormalizing effects of various psychotropic drugs on the individual motor behavior. The computerized locomotor movement-pattern analysis suggests that hyperlocomotion and tachykinesia could be viewed as objectively measurable biomarkers of increased physiological and emotional arousal, supposedly attributable to dopaminergic hyperactivity and/or amygdala hyperactivation, while hypolocomotion and bradykinesia indicate the opposite neurobiological and psychological dysregulation. Analogies with the prominent role of locomotor measures in some well-known animal models of psychiatric disorders advocate for a promising objective translational research in the so far over-subjective fields of psychiatry and clinical psychopharmacology. Most important clinical and theoretical implications of the new approach are discussed.


Motor behavior Motion analysis Psychiatric disorders Biomarkers Early detection Personalized treatment monitoring 


  1. 1.
    Claussen C-F. Cranio-corpo-graphy: 30 years of equilibriometric measurements of spatial and temporal head, neck and trunk movements. In: Claussen C-F, Haid CT, Hofferberth B, editors. Equilibrium research, clinical equilibriometry and modern treatment. Amsterdam: Elsevier; 2000. p. 249–59.Google Scholar
  2. 2.
    Claussen CF, Constantinescu L. Equilibriometric investigations. In: De Sa Souza SG, Claussen C-F, editors. Modern concepts in neurootology. Mumbai: Prajakta Arts; 1997. p. 143–87.Google Scholar
  3. 3.
    Haralanov S, Claussen C-F, Schneider D, Haralanov L, Carvalho C, Stamenov B. Cranio-corpo-graphy: possibilities and perspectives in the field of clinical equilibriometry. Neurol Balkanica. 1997;1:30–4.Google Scholar
  4. 4.
    Haralanov S, Claussen C-F, Haralanova E, Milushev E. Computerized ultrasonographic cranio-corpo-graphy for equilibriometric measurements in multiple sclerosis patients. J Indian Soc Otolaryngol. 2002;1(1):22–4.Google Scholar
  5. 5.
    Haralanov S, Claussen C-F, Schneider D. Evaluation of subjective vestibular symptoms: a problem on the borderline between neurootology and psychiatry. Neurootol Newslett. 2000;5(1):7–11.Google Scholar
  6. 6.
    Haralanov S, Haralanov L. Vertigo, tinnitus and hallucinations due to head trauma. In: Claussen C-F, Kirtane MV, editors. Vertigo, nausea, tinnitus and hypoacusia due to head and neck trauma. Amsterdam: Elsevier Science Publishers; 1991. p. 363–6.Google Scholar
  7. 7.
    Haralanov S, Haralanov L. Vertigo as a hallucinatory phenomenon due to temporal lobe pathology in psychiatric and neurologic patients. In: Claussen C-F, Kirtane M, Schneider D, editors. Vertigo, tinnitus, nausea and hypoacusia due to central disequilibrium. Hamburg: Medicin + Pharmacie Dr. Werner Rudat & Co.; 1994. p. 563–6.Google Scholar
  8. 8.
    Haralanov S, Shkodrova D. Psychiatric aspects of vertigo: clinical and therapeutical problems. In: Claussen C-F, Kirtane M, Schneider D, editors. Vertigo, tinnitus, nausea and hypoacusia due to central disequilibrium. Hamburg: Medicin + Pharmacie Dr. Werner Rudat & Co.; 1994. p. 557–61.Google Scholar
  9. 9.
    Claussen C-F, Haralanov S. Cranio-corpo-graphy for objective monitoring of alcohol withdrawal syndrome. Neurootol Newslett. 2002;6(1):60–1.Google Scholar
  10. 10.
    Haralanov S, Milushev E, Claussen C-F. Stato-kinetic disturbances in multiple sclerosis patients: objective recording and quantitative assessment by computerized ultrasound cranio-corpo-graphy. Bulg Neurol. 2001;1(2):50–1.Google Scholar
  11. 11.
    Haralanov S, Milushev E, Claussen C-F. Neuromotor and psychomotor disturbances in schizophrenic patients: objective recording and quantitative assessment by computerized ultrasound cranio-corpo-graphy. Bulg Neurol. 2001;1(2):55–6.Google Scholar
  12. 12.
    Haralanov S, Claussen C-F, Haralanova E, Shkodrova D. Computerized ultrasonographic cranio-corpo-graphy and abnormal psychomotor activity in psychiatric patients. Int Tinnitus J. 2002;8(2):72–6.PubMedGoogle Scholar
  13. 13.
    Haralanov S, Milushev E, Haralanova E, Claussen C-F. Computerized ultrasound cranio-corpo-graphy for objective and quantitative monitoring of the physical therapy and rehabilitation in patients with movement disorders. Phys Med Rehab Health. 2003;3:15–8.Google Scholar
  14. 14.
    Haralanov S, Milushev E, Haralanova E, Claussen C-F, Shkodrova D. Computerized ultrasound cranio-corpo-graphy for objective and quantitative monitoring of neuroleptics-induced parkinsonism in schizophrenia. In: Chalmanov V, Tsonev V, editors. Actual problems of parkinsonism. Sofia: Academic Publishing House “Prof Marin Drinov”; 2003. p. 170–4.Google Scholar
  15. 15.
    Haralanov S, Haralanova E, Shkodrova D. Objectively measurable equilibriometric dysmetria in schizophrenia: a novel approach to the disease process in the brain. Bulg Neurol Psychiatr Pract. 2007;2:16–23.Google Scholar
  16. 16.
    Haralanov S, Terziivanova P. Contrasting psychomotor dysfunctions in unipolar and bipolar depression: objective quantification by computerized ultrasound cranio-corpo-graphy. Bulg Neurol Psychiatr Pract. 2010;1:18–24.Google Scholar
  17. 17.
    Haralanov S, Terziivanova P. Subclinical psychomotor heterogeneity in unipolar and bipolar depression: objective quantification by computerized ultrasound cranio-corpo-graphy. Bulg Neurol Psychiatr Pract. 2010;3–4:22–31.Google Scholar
  18. 18.
    Haralanov S, Terziivanova P. Subclinical bipolarity in unipolar depression: objective revealing by computerized ultrasonographic cranio-corpo-graphy. Bulg Med. 2011;1(3–4):14–25.Google Scholar
  19. 19.
    Jenkov V, Haralanov S. Use of computerized ultrasonic cranio-corpo-graphy for monitoring of alcohol withdrawal syndrome by measurement of the equilibrium. C R Acad Bulg Sci. 2013;66(8):1139–44.Google Scholar
  20. 20.
    Jenkov V, Haralanov S. Use of ultrasonic cranio-corpo-graphy for assessment of alcohol withdrawal. J Biomed Clin Res. 2014;7(Suppl 1):16.Google Scholar
  21. 21.
    Milushev E, Haralanov S, Rangelov T. Ultrasound cranio-corpo-graphy: prospects and perspectives. Bulg Neurol. 2015;16(Suppl 1):105–6.Google Scholar
  22. 22.
    Haralanov S, Claussen C-F, Shkodrova D, Haralanov L, Schneider D, Carvalho C. Cranio-corpo-graphy in schizophrenic patients. In: Claussen C-F, Sakata E, Itoh A, editors. Vertigo, nausea, tinnitus and hearing loss in central and peripheral vestibular diseases. Amsterdam: Elsevier; 1995. p. 325–8.Google Scholar
  23. 23.
    Haralanov S, Shkodrova D, Claussen C-F. Cranio-corpo-graphic findings in schizophrenic patients. Neurootol Newslett. 2002;6(1):27–31.Google Scholar
  24. 24.
    Morton SM, Bastian AJ. Cerebellar control of balance and locomotion. Neuroscientist. 2004;10(3):247–59.PubMedGoogle Scholar
  25. 25.
    Sokolov AA, Miall RC, Ivry RB. The cerebellum: adaptive prediction for movement and cognition. Trends Cogn Sci. 2017;21(5):313–32.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Ilg W, Golla H, Thier P, Giese MA. Specific influences of cerebellar dysfunctions on gait. Brain. 2007;130(Pt 3):786–98.PubMedGoogle Scholar
  27. 27.
    Woollacott MH, Shumway-Cook A. Attention and the control of posture and gait: a review of an emerging area of research. Gait Posture. 2002;16:1–14.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Shkodrova D, Claussen C-F. Vertigo and anxiety: a problem on the borderline between neurootology and psychiatry. Neurootol Newslett. 2002;6(1):94–8.Google Scholar
  29. 29.
    Shkodrova D, Claussen C-F, Haralanov S. Vertigo and panic disorder: clinical aspects. Neurootol Newslett. 2002;6(2):100–4.Google Scholar
  30. 30.
    Shkodrova D, Haralanov S, Claussen C-F, Tanchev O, Carvalho C. Anxiety disorders and vertigo complaints. In: Regional Meeting of the World Federation of Societies of Biological Psychiatry (Abstracts), Porto; 1994. p. 98.Google Scholar
  31. 31.
    Tanchev O, Claussen C-F, Haralanov S. Functional vertigo and masked depression. Neurootol Newslett. 2000;5(1):12–6.Google Scholar
  32. 32.
    Tanchev O, Haralanov S, Claussen C-F, Carvalho C. Masked depression: neurootological aspects. In: Regional Meeting of the World Federation of Societies of Biological Psychiatry (Abstracts), Porto; 1994; p. 51.Google Scholar
  33. 33.
    Haralanov S, Haralanova E. Dissecting schizotaxia from psychosis in schizophrenia: clinical and theoretical implications. Arch Philos Ment Health. 2009;1:63–4.Google Scholar
  34. 34.
    Haralanov S, Haralanova E, Shkodrova D. Equilibriometric ataxia in schizophrenia: clinical and theoretical implications. Neurol Psychiatry. 2007;3:13–6.Google Scholar
  35. 35.
    Haralanov S, Haralanova E, Shkodrova D, Claussen C-F. Cerebellar signs of the schizophrenic process: clinical and theoretical implications. Neurol Psychiatry. 2009;1:18–21.Google Scholar
  36. 36.
    Dzhupanov G, Haralanov S, Terziivanova P, Haralanova E. Objectively measurable equilibriometric locomotor ataxia in schizophrenia. Eur Psychiatry. 2017;41:S810.Google Scholar
  37. 37.
    Shkodrova D, Haralanova E, Haralanov S. Objective cerebellar signs in schizophrenia: motor and balance coordination deficits. Bulg Neurol Psychiatr Pract. 2007;4:18–24.Google Scholar
  38. 38.
    Haralanova E, Haralanov S, Shkodrova D. Schizophrenia, schizotaxia and cerebellar ataxia: the history of multidisciplinary studies bridging the gap between psychiatric and neurological disorders. In: Abstract Book of the 3rd Balkan Congress on the History of Medicine, 2007; p. 51.Google Scholar
  39. 39.
    Haralanov S, Shkodrova D, Haralanova E, Claussen C-F. Schizophrenia as a movement disorder: evidence from cranio-corpo-graphic movement-pattern analyses. In: Abstracts of the 36th International Danube Symposium for Neurological Sciences and Continuing Education. Sofia; 2004; p. 72.Google Scholar
  40. 40.
    Angyal A, Blackman N. Vestibular reactivity in schizophrenia. Arch Neurol Psychiatr. 1940;44:611–20.Google Scholar
  41. 41.
    Angyal A, Sherman N. Postural reactions to vestibular stimulation in schizophrenic and normal subjects. Am J Psychiatry. 1942;98:857–62.Google Scholar
  42. 42.
    Brahu TS. Audiometric and vestibular function studies in schizophrenia. In: Claussen C-F, Kirtane MV, editors. Optokinetic tests. Hamburg: Dr Werner Rudat & Co.; 1983. p. 37–47.Google Scholar
  43. 43.
    Fitzgerald G, Stengel E. Vestibular reactivity to caloric stimulation in schizophrenics. J Ment Sci. 1945;91:93–100.Google Scholar
  44. 44.
    Meehl PE. Toward an integrated theory of schizotaxia, schizotypy, and schizophrenia. J Personal Disord. 1990;4:1–99.Google Scholar
  45. 45.
    Ornitz EM. Vestibular dysfunction in schizophrenia and childhood autism. Compr Psychiatry. 1970;11(2):159–73.PubMedGoogle Scholar
  46. 46.
    Haralanova E, Haralanov S, Shkodrova D. History of the schizotaxia concept: a model for the integration of neurosciences. Int Ann Hist Gen Theory Med “Asclepius”. 2006;19:179–85.Google Scholar
  47. 47.
    Lenzenweger MF. Schizotaxia, schizotypy, and schizophrenia: Paul E. Meehl’s blueprint for the experimental psychopathology and genetics of schizophrenia. J Abnorm Psychol. 2006;115(2):195–200.PubMedGoogle Scholar
  48. 48.
    Meehl PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol. 1962;17(12):827–38.Google Scholar
  49. 49.
    Haralanov S, Terziivanova P. Psychomotor and dopaminergic bipolarity in unipolar depression: experimental findings, conceptual analysis and implications for treatment strategies. In: Columbus AM, editor. Advances in psychology research, vol. 107. New York: Nova Science Publishers; 2015. p. 145–60.Google Scholar
  50. 50.
    Claussen C-F, Haralanov S. Method for evaluating a movement pattern. US Patent 6,473,717; 2002.Google Scholar
  51. 51.
    Haralanov S, Milushev E, Haralanova E, Shkodrova D, Claussen CF. Objective quantification of equilibriometric coordination deficits in multiple sclerosis patients. In: Abstracts of the 36th International Danube Symposium for Neurological Sciences and Continuing Education. Sofia. 2004. p. 62–3.Google Scholar
  52. 52.
    Haralanov S, Haralanova E, Shkodrova D. Endophenotypes and neurodynamic biomarkers in schizophrenia. Neurol Psychiatry. 2007;2:14–8.Google Scholar
  53. 53.
    Haralanov S, Haralanova E, Shkodrova D, Svinarov DA. Analysis of movement patterns as a pharmacodynamic biomarker in schizophrenia. Ther Drug Monit. 2011;33(4):482.Google Scholar
  54. 54.
    Haralanov S, Haralanova E, Shkodrova D, Svinarov DA. Equilibriometric movement pattern analysis as a pharmacodynamic biomarker in schizophrenia. Basic Clin Pharmacol Toxicol. 2011;109(Suppl.1):40.Google Scholar
  55. 55.
    Haralanov S, Haralanova E, Shkodrova D, Svinarov DA, Claussen C-F. Objective equilibriometric approach in schizophrenia: methodological aspects. Psychiatry. 2009;25(1):17–29.Google Scholar
  56. 56.
    Haralanova E, Haralanov S, Shkodrova D. Objectively measurable pharmacodynamic biomarker for antipsychotic treatment monitoring in schizophrenia. Bulg Neurol Psychiatr Pract. 2007;3:18–22.Google Scholar
  57. 57.
    Haralanova E, Haralanov S, Shkodrova D, Claussen C-F. Objective equilibriometric pharmacodynamic monitoring of the maintenance treatment in schizophrenia. Neurol Psychiatry. 2008;4:19–23.Google Scholar
  58. 58.
    Haralanova E, Haralanov S, Shkodrova D, Svinarov D. Pharmacodynamic biomarkers for optimizing antipsychotic pharmacotherapy in schizophrenia. Neurol Psychiatry. 2011;1:28–32.Google Scholar
  59. 59.
    Haralanova E, Haralanov S, Shkodrova D. The role of cerebellum in the theory of schizophrenia. Neurol Psychiatry. 2006;2:20–3.Google Scholar
  60. 60.
    Haralanov S, Terziivanova P. Psychomotor disturbances in bipolar and unipolar depression. J Czech Slovak Psychiatry. 2008;104(Suppl.2):1230.Google Scholar
  61. 61.
    Terziivanova P, Haralanov S. Latent bipolarity in unipolar depression: objectively measurable manic components in the psychomotor activity and reactivity. In: XVIII Annual Conference of the Bulgarian Psychiatric Association. Hyssar; 2010; p. 35–7.Google Scholar
  62. 62.
    Terziivanova P, Haralanov S. Latent bipolarity in unipolar depression: experimental findings, conceptual analysis and implications for treatment strategies. Folia Med. 2014;56(4):282–8.Google Scholar
  63. 63.
    Haralanov S, Shkodrova D, Claussen C-F, Haralanova E. Objective recording and quantitative analysis of psychomotor disturbances by cranio-corpo-graphy. Psychiatr News. 2000;8:1–8.Google Scholar
  64. 64.
    Haralanov S, Haralanova E, Shkodrova D, Svinarov DA. Objective control of the maintenance treatment in schizophrenia. Neurol Psychiatry. 2008;3:20–4.Google Scholar
  65. 65.
    Haralanov S, Shkodrova D, Haralanova E. Objective monitoring of antipsychotic treatment. Eur Neuropsychopharmacol. 2007;17(Suppl.3):S143.Google Scholar
  66. 66.
    Haralanov S, Shkodrova D, Haralanova E, Claussen C-F. Objective and quantitative monitoring of antipsychotic treatment by cranio-corpo-graphy. Psychiatr News. 2001;9:1–5.Google Scholar
  67. 67.
    Haralanov S, Svinarov D, Shkodrova D, Haralanova E, Claussen C-F. A concept for pharmacokinetic/pharmacodynamic monitoring in schizophrenic patients. Int J Neuropsychopharmacol. 2004;7(Suppl.1):S431.Google Scholar
  68. 68.
    Haralanova E, Haralanov S, Shkodrova D. Pharmacotherapy and pharmacodynamic biomarkers in psychiatry. Neurol Psychiatry. 2007;1:20–3.Google Scholar
  69. 69.
    Svinarov DA, Haralanov S, Claussen C-F. A concept for PK/PD monitoring in psychiatry. Ther Drug Monit. 2003;25(4):532.Google Scholar
  70. 70.
    Svinarov DA, Haralanov S, Claussen C-F. Joint pharmacokinetic/pharmacodynamic (PK/PD) monitoring in psychiatry: a concept and pilot study in schizophrenic patients treated with Risperidon-depot. Clin Exp Pharmacol Physiol. 2004;31(Suppl):A58.Google Scholar
  71. 71.
    Terziivanova P, Haralanov S. Quantitative monitoring of psychomotor activity during pharmacological treatment of depressive episodes. J Biomed Clin Res. 2014;7(Suppl 1):15.Google Scholar
  72. 72.
    Terziivanova P, Haralanov S, Haralanova E, Dzhupanov G. Objective quantification of psychomotor dynamics during pharmacological treatment of bipolar depression. Eur Psychiatry. 2017;41:S212–3.Google Scholar
  73. 73.
    Lally J, MacCabe JH. Personalised approaches to pharmacotherapy for schizophrenia. Br J Psychiatry Adv. 2016;22:78–86.Google Scholar
  74. 74.
    Wium-Andersen IK, Vinberg M, Kessing LV, McIntyre RS. Personalized medicine in psychiatry. Nord J Psychiatry. 2017;71(1):12–9.PubMedGoogle Scholar
  75. 75.
    Fernandes BS, Williams LM, Steiner J, Leboyer M, Carvalho AF, Berk M. The new field of ‘precision psychiatry’. BMC Med. 2017;15(1):80.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Insel TR. The NIMH research domain criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry. 2014;171:395–7.PubMedGoogle Scholar
  77. 77.
    Bernard JA, Mittal VA. Updating the research domain criteria: the utility of a motor dimension. Psychol Med. 2015;45(13):2685–9.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Garvey MA, Cuthbert BN. Developing a motor systems domain for the NIMH RDoC program. Schizophr Bull. 2017;43(5):935–6.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Hengartner MP, Lehmann SN. Why psychiatric research must abandon traditional diagnostic classification and adopt a fully dimensional scope: two solutions to a persistent problem. Front Psych. 2017;8:101.Google Scholar
  80. 80.
    Kapur S, Phillips AG, Insel TR. Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Mol Psychiatry. 2012;17(12):1174–9.PubMedGoogle Scholar
  81. 81.
    Song M, Yang Z, Sui J, Jiang T. Biological subtypes bridge diagnoses and biomarkers: a novel research track for mental disorders. Neurosci Bull. 2017;33(3):351–3.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Perkovic MN, Erjavec GN, Strac DS, Uzun S, Kozumplik O, Pivac N. Theranostic biomarkers for schizophrenia. Int J Mol Sci. 2017;18(4):733.Google Scholar
  83. 83.
    Gargiulo ÁJM, Gargiulo MML, Gargiulo API, Martin GMG, de Gargiulo AIL, Mesones-Arroyo HL, Gargiulo PÁ. Biological markers in psychiatry and its relation with translational approaches: brief historical review. In: Gargiulo PA, Mesones Arroyo HL, editors. Psychiatry and neuroscience update. Switzerland: Springer International Publishing; 2015. p. 311–33.Google Scholar
  84. 84.
    Terziivanova P, Haralanov S. Epistemological and methodological significance of quantitative studies of psychomotor activity for the explanation of clinical depression. J Eval Clin Pract. 2012;18:1151–5.PubMedGoogle Scholar
  85. 85.
    Terziivanova P, Haralanov S. Psychomotor retardation and agitation in clinical depression. In: Stoyanov D, editor. Psychopathology: theory, perspectives and future approaches. New York: Nova Science Publishers; 2013. p. 283–98.Google Scholar
  86. 86.
    Bervoets C, Docx L, Sabbe B, Vermeylen S, Van Den Bossche MJ, Morsel A, Morrens M. The nature of the relationship of psychomotor slowing with negative symptomatology in schizophrenia. Cogn Neuropsychiatry. 2014;19(1):36–46.PubMedGoogle Scholar
  87. 87.
    Chapman JJ, Roberts JA, Nguyen VT, Breakspear M. Quantification of free-living activity patterns using accelerometry in adults with mental illness. Sci Rep. 2017;7:43174.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Cheniaux E, Filgueiras A, Silva R de A, Silveira LA, Nunes AL, Landeira-Fernandez J. Increased energy/activity, not mood changes, is the core feature of mania. J Affect Disord. 2014;152–4:256–61.Google Scholar
  89. 89.
    Docx L, Sabbe BG, Koning J, Mentzel TQ, van Harten PN, Morrens M. Instrumental registration of psychomotor symptoms in schizophrenia: has the time come to use the technique in clinical practice? Tijdschr Psychiatr. 2015;57(2):148–53.PubMedGoogle Scholar
  90. 90.
    Kim J, Nakamura T, Kikuchi H, Sasaki T, Yamamoto Y. Co-variation of depressive mood and locomotor dynamics evaluated by ecological momentary assessment in healthy humans. PLoS One. 2013;8(9):e74979.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Machado-Vieira R, Luckenbaugh DA, Ballard ED, Henter ID, Tohen M, Suppes T, Zarate CA Jr. Increased activity or energy as a primary criterion for the diagnosis of bipolar mania in DSM-5: findings from the STEP-BD study. Am J Psychiatry. 2017;174(1):70–6.PubMedGoogle Scholar
  92. 92.
    Perry W, McIlwain M, Kloezeman K, Henry BL, Minassian A. Diagnosis and characterization of mania: quantifying increased energy and activity in the human behavioral pattern monitor. Psychiatry Res. 2016;240:278–83.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Perry W, Minassian A, Henry B, Kincaid M, Young JW, Geyer MA. Quantifying over-activity in bipolar and schizophrenia patients in a human open field paradigm. Psychiatry Res. 2010;178(1):84–91.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Walther S. Psychomotor symptoms of schizophrenia map on the cerebral motor circuit. Psychiatry Res. 2015;233(3):293–8.PubMedGoogle Scholar
  95. 95.
    Walther S, Morrens M. Editorial: psychomotor symptomatology in psychiatric illnesses. Front Psychiatry. 2015;6:81.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Abboud R, Noronha C, Diwadkar VA. Motor system dysfunction in the schizophrenia diathesis: neural systems to neurotransmitters. Eur Psychiatry. 2017;44:125–33.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Ayehu M, Shibre T, Milkias B, Fekadu A. Movement disorders in neuroleptic-naïve patients with schizophrenia spectrum disorders. BMC Psychiatry. 2014;14:280.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Bernard JA, Mittal VA. Cerebellar-motor dysfunction in schizophrenia and psychosis-risk: the importance of regional cerebellar analysis approaches. Front Psychiatry Schizophr. 2014;5:1–14.Google Scholar
  99. 99.
    Bracht T, Heidemeyer K, Koschorke P, Horn H, Razavi N, Wopfner A, Strik W, Walther S. Comparison of objectively measured motor behavior with ratings of the motor behavior domain of the Bern Psychopathology Scale (BPS) in schizophrenia. Psychiatry Res. 2012;198(2):224–9.PubMedGoogle Scholar
  100. 100.
    Bracht T, Schnell S, Federspiel A, Razavi N, Horn H, Strik W, Wiest R, Dierks T, Müller TJ, Walther S. Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia. Schizophr Res. 2013;143(2–3):269–76.PubMedGoogle Scholar
  101. 101.
    Callaway DA, Perkins DO, Woods SW, Liu L, Addington J. Movement abnormalities predict transitioning to psychosis in individuals at clinical high risk for psychosis. Schizophr Res. 2014;159(2–3):263–6.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Compton MT, Fantes F, Wan CR, Johnson S, Walker EF. Abnormal movements in first-episode, nonaffective psychosis: dyskinesias, stereotypies, and catatonic-like signs. Psychiatry Res. 2015;226(1):192–7.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Dean DJ, Samson AT, Newberry R, Mittal VA. Motion energy analysis reveals altered body movement in youth at risk for psychosis. Schizophr Res. 2017; [Epub ahead of print].Google Scholar
  104. 104.
    Hirjak D, Northoff G, Thomann PA, Kubera KM, Wolf RC. Genuine motor phenomena in schizophrenic psychoses: theoretical background and definition of context. Nervenarzt. 2017. [Epub ahead of print].Google Scholar
  105. 105.
    Hirjak D, Thomann PA, Kubera KM, Wolf ND, Sambataro F, Wolf RC. Motor dysfunction within the schizophrenia-spectrum: a dimensional step towards an underappreciated domain. Schizophr Res. 2015;169(1–3):217–33.PubMedGoogle Scholar
  106. 106.
    Hirjak D, Wolf RC, Wilder-Smith EP, Kubera KM, Thomann PA. Motor abnormalities and basal ganglia in schizophrenia: evidence from structural magnetic resonance imaging. Brain Topogr. 2015;28(1):135–52.PubMedGoogle Scholar
  107. 107.
    Indic P, Salvatore P, Maggini C, Ghidini S, Ferraro G, Baldessarini RJ, Murray G. Scaling behavior of human locomotor activity amplitude: association with bipolar disorder. PLoS One. 2011;6(5):e20650.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Koning JP, Kahn RS, Tenback DE, Van Schelven LJ, Van Harten PN. Movement disorders in nonpsychotic siblings of patients with nonaffective psychosis. Psychiatry Res. 2011;188:133–7.PubMedGoogle Scholar
  109. 109.
    Lallart E, Jouvent R, Herrmann FR, Perez-Diaz F, Lallart X, Beauchet O, Allali G. Gait control and executive dysfunction in early schizophrenia. J Neural Transm (Vienna). 2014;121(4):443–50.Google Scholar
  110. 110.
    Minassian A, Henry BL, Geyer MA, Paulus MP, Young JW, Perry W. The quantitative assessment of motor activity in mania and schizophrenia. J Affect Disord. 2009;120(1–3):200–6.Google Scholar
  111. 111.
    Minassian A, Young JW, Cope ZA, Henry BL, Geyer MA, Perry W. Amphetamine increases activity but not exploration in humans and mice. Psychopharmacology. 2016;233(2):225–33.PubMedGoogle Scholar
  112. 112.
    Mittal VA. Cross-cutting advancements usher in a new era for motor research in psychosis. Schizophr Bull. 2016;42(6):1322–5.PubMedPubMedCentralGoogle Scholar
  113. 113.
    Mittal VA, Bernard JA, Northoff G. What can different motor circuits tell us about psychosis? An RDoC perspective. Schizophr Bull. 2017;43(5):949–55.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Morrens M, Docx L, Walther S. Beyond boundaries: in search of an integrative view on motor symptoms in schizophrenia. Front Psych. 2014;5:145.Google Scholar
  115. 115.
    Ohashi K, Yamamoto Y, Teicher MH. Locomotor micro-activities associated with therapeutic responses in patients with seasonal affective disorders. Integr Med Int. 2015;1(3):151–61.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Peralta V, Campos MS, De Jalon EG, Cuesta MJ. Motor behavior abnormalities in drug-naive patients with schizophrenia spectrum disorders. Mov Disord. 2010;25(8):1068–76.PubMedGoogle Scholar
  117. 117.
    Peralta V, Cuesta MJ. Motor abnormalities: from neurodevelopmental to neurodegenerative through “functional” (neuro)psychiatric disorders. Schizophr Bull. 2017;43(5):956–71.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Sano W, Nakamura T, Yoshiuchi K, Kitajima T, Tsuchiya A, Esaki Y, Yamamoto Y, Iwata N. Enhanced persistency of resting and active periods of locomotor activity in schizophrenia. PLoS One. 2012;7(8):e43539.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Schiffman J. Motor issues in the clinical high risk phase of psychosis. Schizophr Bull. 2017;43(5):937–8.PubMedPubMedCentralGoogle Scholar
  120. 120.
    Schiffman J, Sorensen HJ, Maeda J, Mortensen EL, Victoroff J, Hayashi K, Michelsen NM, Ekstrom M, Mednick S. Childhood motor coordination and adult schizophrenia spectrum disorders. Am J Psychiatry. 2009;166(9):1041–7.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Turner R, Schiavetto A. The cerebellum in schizophrenia: a case of intermittent ataxia and psychosis – clinical, cognitive, and neuroanatomical correlates. J Neuropsychiatry Clin Neurosci. 2004;16:400–8.PubMedGoogle Scholar
  122. 122.
    van Harten PN, Bakker PR, Mentzel CL, Tijssen MA, Tenback DE. Movement disorders and psychosis, a complex marriage. Front Psych. 2015;5:190.Google Scholar
  123. 123.
    van Harten PN, Walther S, Kent JS, Sponheim SR, Mittal VA. The clinical and prognostic value of motor abnormalities in psychosis, and the importance of instrumental assessment. Neurosci Biobehav Rev. 2017;80:476–87.PubMedGoogle Scholar
  124. 124.
    Varambally S, Venkatasubramanian G, Thirthalli J, Janakiramaiah N, Gangadhar BN. Cerebellar and other neurological soft signs in antipsychotic-naive schizophrenia. Acta Psychiatr Scand. 2006;114(5):352–6.PubMedGoogle Scholar
  125. 125.
    Waddington JL, O’Tuathaigh CM. Modelling the neuromotor abnormalities of psychotic illness: putative mechanisms and systems dysfunction. Schizophr Res. 2017; [Epub ahead of print].Google Scholar
  126. 126.
    Walther S, Horn H, Razavi N, Koschorke P, Muller TJ, Strik W. Quantitative motor activity differentiates schizophrenia subtypes. Neuropsychobiology. 2009;60:80–6.PubMedGoogle Scholar
  127. 127.
    Walther S, Koschorke P, Horn H, Strik W. Objectively measured motor activity in schizophrenia challenges the validity of expert ratings. Psychiatry Res. 2009;169:187–90.PubMedGoogle Scholar
  128. 128.
    Walther S, Ramseyer F, Horn H, Strik W, Tschacher W. Less structured movement patterns predict severity of positive syndrome, excitement, and disorganization. Schizophr Bull. 2014;40(3):585–91.PubMedGoogle Scholar
  129. 129.
    Walther S, Stegmayer K, Federspiel A, Bohlhalter S, Wiest R, Viher PV. Aberrant hyperconnectivity in the motor system at rest is linked to motor abnormalities in schizophrenia spectrum disorders. Schizophr Bull. 2017;43(5):982–92.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Walther S, Stegmayer K, Horn H, Rampa L, Razavi N, Muller TJ, Strik W. The longitudinal course of gross motor activity in schizophrenia – within and between episodes. Front Psych. 2015;6:10.Google Scholar
  131. 131.
    Whitty PF, Owoeye O, Waddington JL. Neurological signs and involuntary movements in schizophrenia: intrinsic to and informative on systems pathobiology. Schizophr Bull. 2009;35(2):415–24.PubMedGoogle Scholar
  132. 132.
    Young JW, Minassian A, Geyer MA. Locomotor profiling from rodents to the clinic and back again. Curr Top Behav Neurosci. 2016;28:287–303.PubMedGoogle Scholar
  133. 133.
    Andreasen NC, Nopoulos P, O’Leary DS, Miller DD, Wassink T, Flaum M. Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry. 1999;46(7):908–20.PubMedGoogle Scholar
  134. 134.
    Andreasen NC, O’Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto LL, et al. Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci U S A. 1996;93(18):9985–90.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Bernard JA, Mittal VA. Dysfunctional activation of the cerebellum in schizophrenia: a functional neuroimaging meta-analysis. Clin Psychol Sci. 2015;3(4):545–66.PubMedGoogle Scholar
  136. 136.
    Bernard JA, Orr JM, Mittal VA. Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis. Neuroimage Clin. 2017;14:622–8.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Hirjak D, Wolf RC, Kubera KM, Stieltjes B, Maier-Hein KH, Thomann PA. Neurological soft signs in recent-onset schizophrenia: focus on the cerebellum. Prog Neuro-Psychopharmacol Biol Psychiatry. 2015;60:18–25.Google Scholar
  138. 138.
    Ho BC, Mola C, Andreasen N. Cerebellar dysfunction in neuroleptic-naïve schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs. Biol Psychiatry. 2004;55(12):1146–53.PubMedGoogle Scholar
  139. 139.
    Levit-Binnun N, Davidovitch M, Golland Y. Sensory and motor secondary symptoms as indicators of brain vulnerability. J Neurodev Disord. 2013;5(1):26.PubMedPubMedCentralGoogle Scholar
  140. 140.
    Lungu O, Barakat M, Laventure S, Debas K, Proulx S, Luck D, Stip E. The incidence and nature of cerebellar findings in schizophrenia: a quantitative review of fMRI literature. Schizophr Bull. 2013;39(4):797–806.PubMedGoogle Scholar
  141. 141.
    Manto M. Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases. J Neuroeng Rehabil. 2009;6:10.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Mittal VA, Dean DJ, Bernard JA, Orr JM, Pelletier-Baldelli A, Carol EE, Gupta T, Turner J, Leopold DR, Robustelli BL, Millman ZB. Neurological soft signs predict abnormal cerebellar-thalamic tract development and negative symptoms in adolescents at high risk for psychosis: a longitudinal perspective. Schizophr Bull. 2014;40(6):1204–15.PubMedGoogle Scholar
  143. 143.
    Mouchet-Mages S, Rodrigo S, Cachia A, Mouaffak F, Olie JP, Meder JF, Oppenheim C, Krebs MO. Correlations of cerebello-thalamo-prefrontal structure and neurological soft signs in patients with first-episode psychosis. Acta Psychiatr Scand. 2011;123(6):451–8.PubMedGoogle Scholar
  144. 144.
    Nopoulos PC, Ceilley JW, Gailis EA, Andreasen NC. An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept. Biol Psychiatry. 1999;46:703–11.PubMedGoogle Scholar
  145. 145.
    Schmahmann JD. The role of cerebellum in affect and psychosis. J Neurolinguistics. 2000;13:189–214.Google Scholar
  146. 146.
    Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. 2004;16(3):367–78.PubMedGoogle Scholar
  147. 147.
    Shinn AK, Baker JT, Lewandowski KE, Öngür D, Cohen BM. Aberrant cerebellar connectivity in motor and association networks in schizophrenia. Front Hum Neurosci. 2015;9:134.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Wiser AK, Andreasen NC, O’Leary DS, Watkins GL, Ponto LLB, Hichwa RD. Dysfunctional cortico-cerebellar circuits cause “cognitive dysmetria” in schizophrenia. Neuroreport. 1998;8:1895–9.Google Scholar
  149. 149.
    Albayrak Y, Akyol ES, Beyazyüz M, Baykal S, Kuloglu M. Neurological soft signs might be endophenotype candidates for patients with deficit syndrome schizophrenia. Neuropsychiatr Dis Treat. 2015;11:2825–31.PubMedPubMedCentralGoogle Scholar
  150. 150.
    Chan RCK, Cui HR, Chu MY, Zhang TH, Wang Y, Wang YI, Li Z, Lui SSY, Wang JJ, Cheung EFC. Neurological soft signs precede the onset of schizophrenia: a study of individuals with schizotypy, ultra-high-risk individuals, and first-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2017; [Epub ahead of print].Google Scholar
  151. 151.
    Ashok AH, Marques TR, Jauhar S, Nour MM, Goodwin GM, Young AH, Howes OD. The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017;22(5):666–79.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Henry BL, Minassian A, Young JW, Paulus MP, Geyer MA, Perry W. Cross-species assessments of motor and exploratory behavior related to bipolar disorder. Neurosci Biobehav Rev. 2010;34(8):1296–306.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Geyer MA, Russo PV, Masten VL. Multivariate assessment of locomotor behavior: pharmacological and behavioral analyses. Pharmacol Biochem Behav. 1986;25(1):277–88.PubMedGoogle Scholar
  154. 154.
    Ossenkopp K, Kavaliers M, Sanberg PR. Measuring movement and locomotion: from invertebrates to humans. New York: Chapman & Hall; 1999.Google Scholar
  155. 155.
    Krebs-Thomson K, Paulus MP, Geyer MA. Effects of hallucinogens on locomotor and investigatory activity and patterns: influence of 5-HT2A and 5-HT2C receptors. Neuropsychopharmacology. 1998;18(5):339–51.PubMedGoogle Scholar
  156. 156.
    Lehmann-Masten VD, Geyer MA. Spatial and temporal patterning distinguishes the locomotor activating effect of dizocilpine and phencyclidine in rats. Neuropharmacology. 1991;30(6):629–36.PubMedGoogle Scholar
  157. 157.
    Maksimovic M, Vekovischeva OY, Aitta-aho T, Korpi ER. Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of GluA1-subunit deficient mice. PLoS One. 2014;9(6):e100188.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Iosa M, Picerno P, Paolucci S, Morone G. Wearable inertial sensors for human movement analysis. Expert Rev Med Devices. 2017; [Epub ahead of print].Google Scholar
  159. 159.
    Kluge F, Gaßner H, Hannink J, Pasluosta C, Klucken J, Eskofier BM. Towards mobile gait analysis: concurrent validity and test-retest reliability of an inertial measurement system for the assessment of spatio-temporal gait parameters. Sensors (Basel). 2017;17(7):E1522.Google Scholar
  160. 160.
    Lynall RC, Zukowski LA, Plummer P, Mihalik JP. Reliability and validity of the protokinetics movement analysis software in measuring center of pressure during walking. Gait Posture. 2017;52:308–11.PubMedGoogle Scholar
  161. 161.
    Müller B, Ilg W, Giese MA, Ludolph N. Validation of enhanced kinect sensor based motion capturing for gait assessment. PLoS One. 2017;12(4):e0175813.PubMedPubMedCentralGoogle Scholar
  162. 162.
    Picerno P. 25 years of lower limb joint kinematics by using inertial and magnetic sensors: a review of methodological approaches. Gait Posture. 2017;51:239–46.PubMedGoogle Scholar
  163. 163.
    Stark DE, Kumar RB, Longhurst CA, Wall DP. The quantified brain: a framework for mobile device-based assessment of behavior and neurological function. Appl Clin Inform. 2016;7(2):290–8.PubMedPubMedCentralGoogle Scholar
  164. 164.
    Washabaugh EP, Kalyanaraman T, Adamczyk PG, Claflin ES, Krishnan C. Validity and repeatability of inertial measurement units for measuring gait parameters. Gait Posture. 2017;55:87–93.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Svetlozar Haralanov
    • 1
    • 2
  • Evelina Haralanova
    • 1
    • 2
  • Emil Milushev
    • 1
    • 3
  • Diana Shkodrova
    • 1
    • 2
  1. 1.Medical UniversitySofiaBulgaria
  2. 2.Department of Psychiatry and Medical PsychologyUniversity Hospital of Neurology and Psychiatry “St. Naum”SofiaBulgaria
  3. 3.Department of NeurologyUniversity Hospital of Neurology and Psychiatry “St. Naum”SofiaBulgaria

Personalised recommendations