Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-05-06T19:48:55.461Z Has data issue: false hasContentIssue false
  • English
  • Français

The abnormal development of drive and guidance mechanisms in the brain: the pathogenesis of schizophrenia

Published online by Cambridge University Press:  24 June 2014

J. J. M. van Hoof
J. J. M. van Hoof*
Affiliation:
G.G.Z. Oost-Brabant, Oss, the Netherlands
*
G.G.Z. Oost-Brabant, Joannes Zwijsenlaan 123, 5342 BT Oss, the Netherlands. Tel. ++ 31 412847055; E-mail: jjm.van.hoof@ggzoostbrabant.nl
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

It remains a mystery as to how genetic and environmental factors cause schizophrenia.

Objective:

To develop a pathophysiological model of schizophrenia that has greater explanatory power than existing hypotheses of the disorder.

Method:

Published findings on schizophrenia are integrated with more recent data from human and animal studies of striatal and cerebellar functions.

Results:

The analysis shows that during phylo- and ontogenesis two primarily motor-control mechanisms are applied at the intentional (limbic) level of functioning to organize emotional and cognitive behavior: one for initiating and dosing (drive) and the other for the representational guidance (guidance) of both movements and intentions. The intentional drive and guidance mechanisms are organized through a ventral, respectively, a dorsal cortical–subcortical circuitry.

Conclusions:

A deficient implementation of these mechanisms at the limbic domain manifests itself as schizophrenia, whereby the heterogeneity in symptomatology is explained by the extent of the remaining cerebral activity and by the degree of indirect activation of these systems. In general, activation manifests itself as positive symptomatology and the absence of such activation as negative symptomatology. The model provides a more comprehensive explanation for existing clinical and epidemiological data than do the current alternatives. It is compatible with the major prevailing views on the illness, such as the theories that regard this as a progressive neurodevelopmental, or a connectivity disorder, or one resulting from a deficient cerebral lateralization, or an interrupted cortico–thalamo–cerebello–cortical circuitry. The model fits with recent theories in evolutionary psychology and evolutionary psychiatry.

Keywords

cerebellumevolutionary psychiatrypathogenesisrankingrepresentational guidanceschizophreniaserially orderingshifting to a new groupingspacingstriatum
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 3 , June 2002 , pp. 134 - 146
Copyright
Copyright © Acta Neuropsychiatrica 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Moises, HW.Genetic models of schizophrenia. In: Den Boer, JA, Westenberg, HGM, Van Praag, HM, eds. Advances in the neurobiology of schizophrenia. Chichester: Wiley J and sons Ltd, 1995: 59–88. Google Scholar
Andreasen, NC. A unitary model of schizophrenia. Bleuler's ‘fragmented phrene’ as schizoencephaly. Arch Gen Psychiatry 1999;56: 781–787. CrossRefGoogle Scholar
Stevens, A, Price, J.Evolutionary psychiatry, a new beginning. London: Routledge, 1996. Google Scholar
Ghez, C.The control of movement. The basal ganglia. In: Kandel, ER, Schwartz, JH, Jessel, TM, eds. Principles of neural science, 3rd edn. Amsterdam: Elsevier, 1991: 534–547. Google Scholar
Van de Bercken, J.Information statistical analysis of social interaction in Java-monkeys applied in the neuro-ethology of the caudate nucleus. Thesis, Catholic University of Nijmegen, Nijmegen, 1979. Google Scholar
Strah, A, Frith, U.Why do autistic individuals show superior performance on the block design task? J Child Psychol Psychiatry 1993;8: 1351–1364. Google Scholar
Stuss, DT, Benson, DF.Frontal lobe lesions and behavior. In: Kertesz, A, ed. Localization in neuropsychology. New York: Academic Press, 1983: 429–454. Google Scholar
Cools, AR.Brain and behaviour. In: Bateson, PPG, Klopfer, PH, eds. Hierarchy of feedback systems and control of input. New York: Plenum Press, 1985: 109–168. Google Scholar
Nagahama, Y, Fukuyama, H, Yamauchi, Het al. Cerebral activation during performance of a card sorting test. Brain 1996; 119: 1667–1675.CrossRefGoogle ScholarPubMed
Owen, AM, Doyon, J, Petrides, M, Evans, AC.Planning and spatial working memory: a positron emission tomography study in humans. Eur J Neurosci 1996;8: 353–364.CrossRefGoogle ScholarPubMed
Freedman, M, Black, S, Ebert, P, Binns, M.Orbito-frontal function, object alternation and perseveration. Cereb Cortex 1998;8: 18–27.CrossRefGoogle Scholar
D'Eposito, M, Aguirre, GK, Zarahn, E, Ballard, D, Shin, RK, Lease, G.Functional MRI studies of spatial and nonspatial working memory. Brain Res Cogn Brain Res 1998;7: 1–13.CrossRefGoogle Scholar
Kinsbourne, M.Asymmetrical function of the brain. Cambridge: Cambridge University Press, 1978. Google Scholar
Goldman-Rakic, P.Circuitry of primate prefrontal cortex and regulation of behaviour by representation knowledge. In: Plum, FX, Mountcastel, V, eds. Higher cortical function: handbook of physiology, vol. 5. Washington, DC: American Physiological Society, 1987: 373–417. Google Scholar
Groenewegen, HJ, Uylings, HBM.The prefrontal cortex and the integration of sensory, limbic and autonomic information. In: Uylings, HBM, Van Eden, CG, De Bruin, JPC, Feenstra, MGP, Pennartz, CMA, eds. Progress in brain research, vol. 126. Amsterdam: Elsevier Science, 1996: 3–28. Google Scholar
Chow, TW, Cummings, JL.Frontal–subcortical circuits. In: Miller, BL, Cummings, JL, eds. The human frontal lobes, functions and disorders. New York: Guilford Press, 1999, 3–26. Google Scholar
Kaufer, DI, Lewis, DA.Frontal lobe anatomy and cortical connectivity. In: Miller, BL, Cummings, JL, eds. The human frontal lobes, functions and disorders. New York: Guilford Press, 1999, 27–44. Google Scholar
Mega, MS, Cummings, JL, Salloway, S, Malloy, P.The limbic system. An anatomic, phylogenetic, and clinical perspective. In: Salloway, S, Malloy, P, Cummings, JL, eds. The neuropsychiatry of limbic and subcortical disorders. Washington, DC: American Psychiatric Press Inc., 1997: 3–18. Google Scholar
Scheibel, AB.The thalamus and neuropsychiatric illness. In: Salloway, S, Malloy, P, Cummings, JL, eds. The neuropsychiatry of limbic and subcortical disorders. Washington, DC: American Psychiatric Press Inc., 1997: 31–42. Google Scholar
Kelly, JP, Dodd, J.Anatomical organization of the nervous system. In: Kandel, ER, Schwartz, JH, Jessel, TM, eds. Principles of neural science, 3rd edn. Amsterdam: Elsevier, 1991: 273–282. Google Scholar
Thacher, RW.Cyclic cortical reorganization. Origins of human cognitive development. In: Dawson, G, Fischer, KW, eds. Human behavior and the developing brain. New York: Guilford Press, 1994: 232–269. Google Scholar
Heimer, L, Alheid, GF, De Olmos, JSet al. The accumbens: beyond the core–shell dichotomy. In: Salloway, S, Malloy, P, Cummings, J L, eds. The neuropsychiatry of limbic and subcortical disorders. Washington, DC: American Psychiatric Press Inc., 1997: 43–69. Google Scholar
Cooper, C, Taylor, R.Personality and performance on a frustrating cognitive task. Percept Mot Skills 1999;88: 1384.CrossRefGoogle ScholarPubMed
Johnson, DL, Wiebe, JS, Gold, SM, et al. Cerebral blood flow and personality. A positron emission tomography study. Am J Psychiatry 1999;156: 252–257.Google ScholarPubMed
Nonneman, AJ, Corwin, JV, Sahley, CL, Vicedomini, JP.Functional development of the prefrontal system. In: Finger, S, Almli, CR, eds. Early brain damage, vol. 2. Orlando: Academic Press, 1984: 138–153. Google ScholarPubMed
Van Eden, CG, Uylings, HBM.Cytoarchitectonic development of the prefrontal cortex in the rat. J Comp Neurol 1985;241: 253–267.CrossRefGoogle ScholarPubMed
Friston, KJ.Schizophrenia and the disconnection hypothesis. Acta Psychiatr Scand 1999;99(suppl. 395):68–79.CrossRefGoogle Scholar
Carlsson, A.The dopamine theory revisited. In: Hirsch, SR, Weinberger, DR, eds. Schizophrenia. Oxford: Blackwell Science, 1995: 379–400. Google ScholarPubMed
Abi-Dargham, A, Rodenhiser, J, Printz, Det al. From the cover: increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 2000;97: 8104–8109.CrossRefGoogle Scholar
Michael, CM, Morris, DP, Soroker, E.Follow-up studies of shy, withdrawn children. Relative incidence of schizophrenia. Am J Orthopsychiatry 1957;27: 331–337. CrossRefGoogle ScholarPubMed
Dworkin, RH, Berstein, G, Kaplansky, LM.Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder. Am J Psychiatry 1991;148: 1182–1188.Google ScholarPubMed
Cannon, TD, Mednick, SA, Parnas, J.Antecedents of predominantly negative and predominantly positive symptom schizophrenia in a high-risk population. Arch Gen Psychiatry 1990;47: 622–632.CrossRefGoogle Scholar
Liddle, PF, Friston, KJ, Frith, CD, Frackowiak, RSJ.Cerebral blood flow and mental processes in schizophrenia. J Roy Soc Med 1992;85: 224–226. Google Scholar
Feinberg, I, Guazelli, M.Schizophrenia: a disorder of the corollary discharge systems that integrate the motor systems of thought with the sensory systems of consciousness. Br J Psychiatry 1999;74: 96–104. Google Scholar
Harvey, PD, Serper, MR.The nature and management of cognitive dysfunction in patients with schizophrenia. Direct Psychiatry 1998;19: 21–35. Google Scholar
Van Hoof, JJM, Jogems-Kosterman, BJM, Sabbe, BGC., Zitman, FGHulstijn, W.Differentiation of cognitive and motor slowing in the digit symbol test (DST): differences between depression and schizophrenia. Psychiatr Res 1998;32: 99–103. CrossRefGoogle Scholar
Cole, JDGoldberg, SCKlerman, GL.Phenothiazine treatment in acute schizophrenia. Arch Gen Psychiatry 1964;10: 246–261. Google Scholar
Marder, RSVan Putten, T.Antipsychotic medications. In: Schatzberg, AFNemeroff, CB, eds. The American Psychiatric Press textbook of psychopharmacology. Washington, DC: American Psychiatric Press, Inc., 1995: 247–262. Google Scholar
Owens, MJRisch, SC.Atypical antipsychotics. In: Schatzberg, AFNemeroff, CB, eds. The American Psychiatric Press textbook of psychopharmacology. Washington, DC: American Psychiatric Press, Inc., 1995: 263–280. Google Scholar
Bunney, BSSesack, SRSilva, NL.Midbrain dopamine systems: neurophysiology and electrophysiological pharmacology. In: Meltzer, HY, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987: 113–126. Google Scholar
Bunney, BSChiodo, LAGrace, AA.Midbrain dopamine system electrophysiological functioning: a review and new hypothesis. Synapse 1991;9: 79–94.CrossRefGoogle ScholarPubMed
Chiodo, LABunney, BS.Typical and atypical neuroleptics. differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 1983;3: 1607–1619.Google ScholarPubMed
Moghaddam, BBunney, BS.Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. J Neurochem 1990;54: 1755–1760.CrossRefGoogle Scholar
Taylor, DG.Advances in the neuropathology of schizophrenia. In: Den Boer, JAWestenberg, HGMVan Praag, HM, eds. Advances in the neurobiology of schizophrenia. Chichester, UK: John Wiley and Sons 1995: 111–130. Google Scholar
Pakkenberg, B.Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical dissectors. Biol Psychiatry 1993;34: 768–772.CrossRefGoogle Scholar
Talamini, LMLouwerens, JWSlooff, CJKorf, J.PET versus postmortem studies in schizophrenia research. Significance for the pathogenesis and pharmacotherapy. In: Den Boer, JAWestenberg, HGMVan Praag, HM, eds. Advances in the neurobiology of schizophrenia. Chichester, UK: John Wiley and Sons, 1995: 157–188. Google Scholar
Truex, RCCarpenter, MB.Human neuroanatomy, 6th edn. Baltimore: Williams & Wilkins Co., 1969: 498–517. Google Scholar
Machon, RAMednick, SASchulsinger, F.The interaction of seasonality, place of birth, genetic risk and subsequent schizophrenia in a high-risk sample. Br J Psychiatry 1983;143: 383–388.CrossRefGoogle Scholar
Faris, REDunham, HW.Mental disorders in urban areas. An ecological study of schizophrenia and other psychoses. New York: Hafner, 1993. Google Scholar
Birchwood, MCochrane, RMacmillan, FCope Stake, SKucharska, JCariss, M.The influence of ethnicity and family structure on relapse in first episode schizophrenia. A comparison of Asian Afro-Caribbean, and white patients. Br J Psychiatry 1992;161: 783–790.CrossRefGoogle ScholarPubMed
Jablensky, A.Schizophrenia: the epidemiological horizon. In: Hirsch, SRWeinberger, DR, eds. Schizophrenia. Oxford: Blackwell Science, 1995: 206–252. Google ScholarPubMed
Ödegaard, O.A statistical investigation of the incidence of mental disorder in Norway. Psychiatr Q 1932;20: 381–401. CrossRefGoogle Scholar
Gamble, C.Timewalkers. The prehistory of global colonization. London: Penguin Group, 1993. Google Scholar
Häfner, HRiecher, AMaurer, K.Geschlachtsunterschiede bei schizophrenen Erkrankungen. Fortschr Neurol Psychiatr 1991;59: 343–396.CrossRefGoogle Scholar
Hambrecht, MMaurer, KHäfner, H.Gender differences in schizophrenia in three cultures. Results of the WMO collaborative study on psychiatric disability. Soc Psychiatr Psychiatr Epidemiol 1992;27: 117–121. Google Scholar
Kelly, DD.Sexual differentiation of the nervous system. In: Kandel, ERSchwarz, JMJessel, TM, eds. Principles of neural science. East Norwalk: Appleton & Lange, 1991: 959–973. Google Scholar
Weinberger, DR.The pathogenesis of schizophrenia: a neurodevelopmental theory. In: Nasrallah, MAWeinberger, DR, eds. The handbook of schizophrenia I. The neurology of schizophrenia. Amsterdam: Elsevier, 1986: 397–406. Google Scholar
Crow, TJBrendl, KBogerts, B.Structural and functional deviations. In: Helmchen, HHenn, FA, eds. Biological perspectives of schizophrenia. New York: Wiley, 1987: 254–269. Google Scholar
Eaton, WWDay, PKramer, M.The use of epidemiology for risk factor research in schizophrenia: an overview and methodological critique. In: Tsuang, MTSimpson, JC, eds. Handbook of schizophrenia, vol. 3. Nosology, epidemiology and genetics of schizophrenia. Amsterdam: Elsevier, 1988: 169–204. Google Scholar
Woods, BT.Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 1998;155: 1661–1670.CrossRefGoogle Scholar
Torrey, EFPeterson, MR.Schizophrenia and the limbic system. Lancet 1974;2: 942–946.CrossRefGoogle ScholarPubMed
Goldman-Rakic, PS.Prefrontal cortical dysfunction in schizophrenia: the relevance of working memory. In: Caroll, BJBarrett, JE, eds. Psychopathology and the brain. New York: Raven Press, 1991: 1–23. Google Scholar
Crow, TJ.Temporal lobe asymmetries as key to the aetiology of schizophrenia. Schizophr Bull 1997;16: 433–443. CrossRefGoogle Scholar
Van Hoof, JJM.‘Motor’ and ‘Spacing’ mechanismen in het brein — de oorzaak van schizofrenie. Van Analyse Tot Zorginnovatie 2000;3: 22–26. Google Scholar
Goldman-Rakic, PS.Working memory dysfunction in schizophrenia. J Neuropsychiatr Clin Neurosci 1994;6: 348–357. Google Scholar
Frith, CD. The cognitive neuropsychology of Schizophrenia. Hillsdale, New Jersey: Lawrence Erlbaum Associates, 1992. Google Scholar
Jogems-Kosterman, BJMZitman, FGVan Hoof, JJMHulstijn, W.Psychomotor slowing and planning deficits in schizophrenia. Schizophr Res 2001;48: 317–333.CrossRefGoogle Scholar
Van Hoof, JJM.Torticollis Spasmodicus en schakelvaardigheid. Een onderzoek naar de invloed van Haloperidol op schakelvaardigheid. Dissertatie. Katholieke Universiteit Nijmegen, Nijmegen, 1986. Google Scholar
Berger, HJCVan Hoof, JJMVan Den Bercken, JHet al. Haloperidol and cognitive shifting. Neuropsychologia 1989;5: 629–639. CrossRefGoogle Scholar
Stober, G, Syagailo, YV, Okladnova, O.Functional Pax-6 gene-linked polymorphic region: potential association with paranoid schizophrenia. Biol Psychiatry 1999;45: 1585–1591.CrossRefGoogle ScholarPubMed
Oliemeulen, EAP, Van Hoof, JJM, Jogems-Kosterman, BJM, Hulstijn, W, Tuynman-Qua, HG.Is olanzapine a substitute for clozapine? The effects on psychomotor performance. Schizophr Res 2000;41/1: 187. CrossRefGoogle Scholar