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16 - The development of “mis-wired” limbic lobe circuitry in schizophrenia and bipolar disorder

Published online by Cambridge University Press:  04 August 2010

By
Francine M. Benes
Edited by
Matcheri S. Keshavan ,
James L. Kennedy  and
Robin M. Murray
Francine M. Benes
Affiliation:
McLean Hospital, Belmont and Harvard Medical School, Boston, USA
Matcheri S. Keshavan
Affiliation:
University of Pittsburgh
James L. Kennedy
Affiliation:
Clarke Institute of Psychiatry, Toronto
Robin M. Murray
Affiliation:
Institute of Psychiatry, London
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Summary

In patients with schizophrenia, a variety of anomalies have been detected in the limbic lobe, a phylogenetically old portion of the cerebral cortex that includes the anterior cingulate region and hippocampal formation. In addition, the basolateral subdivision of the amygdala, another component of the limbic lobe, has been implicated in the pathophysiology of psychotic disorders, in part because it sends important inputs to the cingulate cortex and hippocampus. The three major components of the limbic lobe play a central role in generating disturbances in motivation, attention, emotion, and social interactions in schizophrenia and bipolar disorder. This chapter describes studies in both human and rodent brains that have contributed to our understanding of how this complex circuitry may be altered during development, leading to the appearance of psychotic disorders during late adolescence and early adulthood. It discusses two particular neurotransmitters: gamma-aminobutyric acid (GABA) and dopamine.

Keywords

amygdalabipolar disorderdopamineschizophrenialimbic lobe circuitrygamma-aminobutyric acid
Type
Chapter
Information
Neurodevelopment and Schizophrenia , pp. 295 - 309
Publisher: Cambridge University Press
Print publication year: 2004

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References

Amaral, D. G., Price, J. L. (1984). Amygdalo-cortical projections in the monkey (macaca fascicularis). JComp Neurol 230: 465–496CrossRefGoogle Scholar
Beasley, C. L., Reynolds, G. P. (1997). Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res 24: 349–355CrossRefGoogle ScholarPubMed
Benes, F. M. (1993). Neurobiological investigations in cingulate cortex of schizophrenic brain. Schizophr Bull 19: 537–549CrossRefGoogle ScholarPubMed
Benes, F. M. (1997). The role of stress and dopamine–GABA interactions in the vulnerability for schizophrenia. J Psychiatr Res 31: 257–275CrossRefGoogle Scholar
Benes, F. M. (1998). Model generation and testing to probe neural circuitry in the cingulate cortex of postmortem schizophrenic brain. Schizophr Bull 24: 219–230CrossRefGoogle ScholarPubMed
Benes, F. M. (2000). Emerging principles of altered neural circuitry in schizophrenia. Brain Res Brain Res Rev 31: 251–269CrossRefGoogle Scholar
Benes, F. M., Majocha, R., Bird, E. D., Marotta, C. A. (1987). Increased vertical axon numbers in cingulate cortex of schizophrenics. Arch Gen Psychiatry 44: 1017–1021CrossRefGoogle ScholarPubMed
Benes, F. M., McSparren, J., Bird, E. D., SanGiovanni, J. P., Vincent, S. L. (1991). Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 48: 996–1001CrossRefGoogle ScholarPubMed
Benes, F. M., Vincent, S. L., Alsterberg, G., Bird, E. D., SanGiovanni, J. P. (1992a). Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J Neurosci 12: 924–929CrossRefGoogle Scholar
Benes, F. M., Sorensen, I., Vincent, S. L., Bird, E. D., Sathi, M. (1992b). Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cereb Cortex 2: 503–512CrossRefGoogle Scholar
Benes, F. M., Vincent, S. L., Molloy, R. (1993). Dopamine-immunoreactive axon varicosities form nonrandom contacts with GABA-immunoreactive neurons of rat medial prefrontal cortex. Synapse 15: 285–295CrossRefGoogle ScholarPubMed
Benes, F. M., Khan, Y., Vincent, S. L., Wickramasinghe, R. (1996a). Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain. Synapse 22: 338–3493.0.CO;2-C>CrossRefGoogle Scholar
Benes, F. M., Vincent, S. L., Molloy, R., Khan, Y. (1996b). Increased interaction of dopamine-immunoreactive varicosities with GABA neurons of rat medial prefrontal cortex occurs during the postweanling period. Synapse 23: 237–2453.0.CO;2-8>CrossRefGoogle Scholar
Benes, F. M., Todtenkopf, M. S., Taylor, J. B. (1997). Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain. Synapse 25: 80–923.0.CO;2-2>CrossRefGoogle ScholarPubMed
Benes, F. M., Kwok, E. W., Vincent, S. L., Todtenkopf, M. S. (1998). A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. [See comments]Biol Psychiatry 44: 88–97CrossRefGoogle Scholar
Benes, F. M., Todtenkopf, M. S., Logiotatos, P., Williams, M. (2000). Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. J Chem Neuroanat 20: 259–269CrossRefGoogle ScholarPubMed
Benes, F. M., Vincent, S. L., Todtenkopf, M. S. (2001). The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects. Biol Psychiatry 50: 395–406CrossRefGoogle ScholarPubMed
Berretta, S., Munno, D. W., Benes, F. M. (2001). Amygdalar activation alters the hippocampal GABA system: “partial” modelling for postmortem changes in schizophrenia. J Comp Neurol 431: 129–1383.0.CO;2-6>CrossRefGoogle Scholar
Brozoski, T., Brown, R. M., Rosvold, H. E., Goldman, P. S. (1979). Cognitive deficit caused by depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205: 929–931CrossRefGoogle ScholarPubMed
Bruinink, A., Lichtensteiner, W., Schlumpf, M. (1983). Pre- and postnatal ontogeny and characterization of dopaminergic D2, serotonergic S2, and spirodecanone binding sites in rat forebrain. J Neurochem 40: 1227–1237CrossRefGoogle ScholarPubMed
Chronwall, B., Wolff, J. R. (1980). Prenatal and postnatal development of GABA-accumulating cells in the occipital neocortex of rat. J Comp Neurol 190: 187–208CrossRefGoogle ScholarPubMed
Coyle, J. T., Enna, S. (1976). Neurochemical aspects of the ontogenesis of GABAnergic neurons in the rat brain. Brain Res 111: 119–133CrossRefGoogle ScholarPubMed
Coyle, J. T., Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders. [Review]Science 262: 689–695CrossRefGoogle Scholar
Cunningham, M. G., Bhattacharyya, S., Benes, F. M. (2002). Amygdalo-cortical sprouting continues into early adulthood: Implications for the development of normal and abnormal function during adolescence. J Comp Neurol 453: 116–130CrossRefGoogle ScholarPubMed
Daviss, S. R., Lewis, D. A. (1995). Local circuit neurons of the prefrontal cortex in schizophrenia: selective increase in the density of calbindin-immunoreactive neurons. Psychiatry Res 59: 81–96CrossRefGoogle ScholarPubMed
Deskin, R., Seidler, F. J., Whitmore, W. L., Slotkin, T. A. (1981). Development of α-noradrenergic and dopaminergic receptor systems depends on maturation of their presynaptic nerve terminals in the rat brain. J Neurochem 36: 1683–1690CrossRefGoogle ScholarPubMed
Fatemi, S. H., Emamian, E. S., Kist, D.et al. (1999). Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Mol Psychiatry 4: 145–154CrossRefGoogle ScholarPubMed
Gambarana, C., Pittman, R., Siegel, R. E. (1990). Development expression of the GABA-A receptor γ 1 subunit mRNA in the rat brain. J Neurobiol 21: 1169–1179CrossRefGoogle ScholarPubMed
Guidotti, A., Auta, J., Davis, J. M.et al. (2000). Decrease in Reelin and glutamate acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder. Arch Gen Psychiatry 57: 1061–1069CrossRefGoogle ScholarPubMed
Heckers, S., Stone, D., Walsh, J.et al. (2002). Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry 59: 521–529CrossRefGoogle Scholar
Impagnatiello, F., Guidotti, A. R., Pesold, C.et al. (1998). A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 95: 15718–15723CrossRefGoogle Scholar
Iritani, S., Kuroki, N., Ikeda, K., Kazamatsuri, H. (1999). Calbindin immunoreactivity in the hippocampal formation and neocortex of schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry 23: 409–421CrossRefGoogle ScholarPubMed
Johnston, M. V. (1988). Biochemistry of neurotransmitters in cortical development. In Cerebral Cortex, ed. E. G. Jones. New York: Plenum Press, pp. 211–236CrossRef
Jones, E. G. (1993). GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 3: 361–372CrossRefGoogle ScholarPubMed
Kalsbeek, A., Voorn, P., Buijs, R. M., Pool, C. W., Uylings, H. B. (1988). Development of the dopaminergic innervation in the prefrontal cortex of the rat. J Comp Neurol 269: 58–72CrossRefGoogle ScholarPubMed
Kalsbeek, A., Matthijssen, M. A., Uylings, H. B. (1989). Morphometric analysis of prefrontal cortical development following neonatal lesioning of the dopaminergic mesocortical projection. Exp Brain Res 78: 279–289CrossRefGoogle ScholarPubMed
Longson, D., Deakin, J. F., Benes, F. M. (1996). Increased density of entorhinal glutamate-immunoreactive vertical fibers in schizophrenia. J Neur Transm 103: 503–507CrossRefGoogle Scholar
Luhmann, H. J., Prince, D. A. (1991). Postnatal maturation of the GABAergic system in rat neocortex. J Neurophysiol 65: 247–263CrossRefGoogle ScholarPubMed
McDonald, A. J., Beitz, A. J., Larson, A. A.et al. (1989). Co-localization of glutamate and tubulin in putative excitatory neurons of the hippocampus and amygdala: an immunohistochemical study using monoclonal antibodies. Neuroscience 30: 405–421CrossRefGoogle ScholarPubMed
McLean, P. D. (1954). Studies on limbic system (visceral brain) and their bearing on psychosomatic problems. In Recent Developments in Psychosomatic Medicine, ed. E. Wittkower, R. Cleghorn. Philadelphia, PA: Lippincott, p. 106
Palacios, J. M., Niehoff, D. L., Kuhar, M. J. (1979). Ontogeny of GABA and benzodiazepine receptors: effects of Triton X-100, bromide and muscimol. Brain Res 179: 390–395CrossRefGoogle ScholarPubMed
Penit-Soria, J., Retaux, S., Maurin, Y. (1989). Effets de la stimulation des recepteurs D1 et D2 dopaminergiques sur la liberation d'acide γ-[3H] aminobutyrique induite electriquement dans le cortex prefrontal du rat. C R Acad Sci Paris 309: 441–446Google Scholar
Perez-Jananay, J. M., Vives, F. (1991). Electrophysiological study of the response of medical prefrontal cortex neurons to stimulation of the basolateral nucleus of the amygdala in the rat. Brain Res 564: 97–101CrossRefGoogle Scholar
Pierri, J. N., Chaudry, A. S., Woo, T. U., Lewis, D. A. (1999). Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects. Am J Psychiatry 156: 1709–1719Google ScholarPubMed
Pitkanen, A., Pikkarainen, M., Nurminen, N., Ylinen, A. (2000). Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat. A review. Ann N Y Acad Sci 911: 369–391CrossRefGoogle ScholarPubMed
Retaux, S., Besson, M. J., Penit-Soria, J. (1991). Opposing effects of dopamine D2 receptor stimulation on the spontaneous and the electrically evoked release of [3H] GABA on rat prefrontal cortex slices. Neuroscience 42: 61–71CrossRefGoogle Scholar
Roth, R. H., Tam, S. Y., Ida, Y., Yang, J. X., Deutch, A. Y. (1988). Stress and the mesocorticolimbic dopamine systems. Ann N Y Acad Sci 537: 138–147CrossRefGoogle ScholarPubMed
Selemon, L. D., Goldman, Rakic P., Rajkowska, G. (2002). 2D versus 3D cell counting. Biol Psychiatry 51: 838–840CrossRefGoogle Scholar
Todtenkopf, M. S., Benes, F. M. (1998). Distribution of glutamate decarboxylase65 immunoreactive puncta on pyramidal and nonpyramidal neurons in hippocampus of schizophrenic brain. Synapse 29: 323–3323.0.CO;2-7>CrossRefGoogle ScholarPubMed
Van Hoesen, G. W., Morecraft, R. J., Vogt, B. A. (1993). Connections of the monkey cingulate cortex. In Neurobiology of Cingulate Cortex and Limbic Thalamus, ed. M. Gabriel. Boston, MA: Birkhauser, pp. 249–284CrossRef
Verney, C., Berger, B., Adrien, J., Vigny, A., Gay, M. (1982). Development of the dopaminergic innervation of the rat cerebral cortex. A light microscopic immunocytochemical study using anti-tyrosine hydroxylase antibodies. Brain Res 281: 41–52CrossRefGoogle ScholarPubMed
Vincent, S. L., Adamec, E., Sorensen, I., Benes, F. M. (1994). The effects of chronic haloperidol administration on GABA-immunoreactive axon terminals in rat medial prefrontal cortex. Synapse 17: 26–35CrossRefGoogle ScholarPubMed
Vincent, S. L., Pabreza, L., Benes, F. M. (1995). Postnatal maturation of GABA-immunoreactive neurons of rat medial prefrontal cortex. J Comp Neurol 355: 81–92CrossRefGoogle ScholarPubMed
Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., Lewis, D. A. (2000). Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57: 237–245CrossRefGoogle Scholar
Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., Lewis, D. A. (2001). GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons. Am J Psychiatry 158: 256–265CrossRefGoogle Scholar
Woo, T. U., Whitehead, R. E., Melchitzky, D. S., Lewis, D. A. (1998). A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA 95: 5341–5346CrossRefGoogle Scholar
Zhang, Z. J., Reynolds, G. P. (2002). A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 55: 1–10CrossRefGoogle Scholar

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