Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-14T15:20:43.125Z Has data issue: false hasContentIssue false

Increased neuronal cell number in the dorsal motor nucleus of the vagus in schizophrenia

Published online by Cambridge University Press:  24 June 2014

Hubertus Axer*
Affiliation:
Department of Neurology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany
Hans-Gert Bernstein
Affiliation:
Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany
Silke Keiner
Affiliation:
Department of Neurology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany
Polina Heronimus
Affiliation:
Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany
Heinrich Sauer
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Philosophenweg 3, D-07747 Jena, Germany
Otto W. Witte
Affiliation:
Department of Neurology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany
Bernhard Bogerts
Affiliation:
Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany
Karl-Jürgen Bär
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Philosophenweg 3, D-07747 Jena, Germany
*
PD Dr. med. Hubertus Axer, Department of Neurology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany. Tel: +49 3641 9323454; Fax: +49 3641 9323402; E-mail: [email protected]

Abstract

Axer H, Bernstein H-G, Keiner S, Heronimus P, Sauer H, Witte OW, Bogerts B, Bär K-J. Increased neuronal cell number in the dorsal motor nucleus of the vagus in schizophrenia.

Objective:

Recently, a reduction in efferent vagal regulation has been found in schizophrenic patients.

Methods:

Therefore, the brainstems of nine schizophrenic patients and nine normal controls were stereologically analysed. The number of neurons using the optical fractionator method and nuclear volumes applying the Cavalieri principle was estimated in Nissl stained sections of the dorsal motor nucleus of the vagus (DMNV) and the hypoglossal nucleus.

Results:

The neurons in the right DMNV were significantly increased in the schizophrenic group compared to normal controls (p = 0.047), while the volumes of the DMNV did not differ. In contrast, no such differences were found in the hypoglossal nucleus.

Conclusion:

Although this pilot study is limited by its small sample size, the analysis of the solitarius–ambiguus–vagus system in schizophrenic patients is an interesting target in schizophrenia research. The most reasonable background for increased neuron numbers in the DMNV could be a system-specific neurodevelopmental disturbance in schizophrenia.

Type
Research Article
Copyright
Copyright © 2010 John Wiley & Sons A/S

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

Brown, S, Inskip, H, Barraclough, B.Causes of the excess mortality of schizophrenia. Br J Psychiatry 2000;177: 212217. CrossRefGoogle ScholarPubMed
Bär, KJ, Letzsch, A, Jochum, T, Wagner, G, Greiner, W, Sauer, H.Loss of efferent vagal activity in acute schizophrenia. J Psychiatr Res 2005;39:519527. CrossRefGoogle ScholarPubMed
Toichi, M, Kubota, Y, Murai, Tet al. The influence of psychotic states on the autonomic nervous system in schizophrenia. Int J Psychophysiol 1999;31:147154. CrossRefGoogle Scholar
Bär, KJ, Boettger, MK, Berger, Set al. Decreased baroreflex sensitivity in acute schizophrenia. J Appl Physiol 2007;102:10511056. CrossRefGoogle ScholarPubMed
Chapleau, MW.Determinants of baroreflex sensitivity in health correlates to causality. Clin Auton Res 2003;13: 310313. CrossRefGoogle ScholarPubMed
Smith, LL, Kukielka, M, Billman, GE.Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction. Am J Physiol Heart Circ Physiol 2005;288:H1763H1769. CrossRefGoogle ScholarPubMed
Suvisaari, JM, Saarni, SI, Perälä, Jet al. Metabolic syndrome among persons with schizophrenia and other psychotic disorders in a general population survey. J Clin Psychiatry 2007;68:10451055. CrossRefGoogle Scholar
Laaksonen, DE, Niskanen, L, Lakka, HM, Lakka, TA, Uusitupa, M.Epidemiology and treatment of the metabolic syndrome. Ann Med 2004;36:332346. CrossRefGoogle ScholarPubMed
De Hert, M, Schreurs, V, Sweers, Ket al. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: A retrospective chart review. Schizophr Res 2008;101:295303. CrossRefGoogle ScholarPubMed
Saddichha, S, Manjunatha, N, Ameen, S, Akhtar, S.Metabolic syndrome in first episode schizophrenia –A randomized double-blind controlled, short-term prospective study. Schizophr Res 2008;101:266272. CrossRefGoogle ScholarPubMed
Ryan, MCM, Collins, P, Thakore, JH.Impaired fasting glucose tolerance in first-episode, drug-naïve patients with schizophrenia. Am J Psychiatry 2003;160:284289. CrossRefGoogle ScholarPubMed
Wang, J, Irnaten, M, Neff, RAet al. Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus. Ann N Y Acad Sci 2001;940:237246. CrossRefGoogle ScholarPubMed
Travagli, RA, Hermann, GE, Browning, KN, Rogers, RC.Brainstem circuits regulating gastric function. Annu Rev Physiol 2006;68: 279305. CrossRefGoogle ScholarPubMed
Cheng, Z, Powley, TL, Schwaber, JS, Doyle III, FJ.Projections of the dorsal motor nucleus of the vagus to cardiac ganglia of rat atria: an anterograde tracing study. J Comp Neurol 1999;410:320341. 3.0.CO;2-5>CrossRefGoogle Scholar
Kalia, M, Mesulam, MM.Brain stem projections of sensory and motor components of the vagus complex in the cat: I. The cervical vagus and nodose ganglion. J Comp Neurol 1980;193:435465. CrossRefGoogle ScholarPubMed
Kalia, M, Mesulam, MM.Brain stem projections of sensory and motor components of the vagus complex in the cat: II. Laryngeal, tracheobronchial, pulmonary, cardiac, and gastrointestinal branches. J Comp Neurol 1980;193: 467508. CrossRefGoogle ScholarPubMed
Huang, XF, Tork, I, Paxinos, G.Dorsal motor nucleus of the vagus nerve: a cyto- and chemoarchitectonic study in the human. J Comp Neurol 1993;330:158182. CrossRefGoogle ScholarPubMed
Fox, EA, Powley, TL.Morphology of identified preganglionic neurons in the dorsal motor nucleus of the vagus. J Comp Neurol 1992;322:7989. CrossRefGoogle ScholarPubMed
Travagli, RA, Rogers, RC.Receptors and transmission in the brain-gut axis: potential for novel therapies V. Fast and slow extrinsic modulation of dorsal vagal complex circuits. Am J Physiol Gastrointest Liver Physiol 2001;281:G595G601. Google ScholarPubMed
Guidotti, A, Auta, J, Davis, JMet al. GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. Psychopharmacology 2005;180:191205. CrossRefGoogle Scholar
Sarter, M, Nelson, CL, Bruno, JP.Cortical cholinergic transmission and cortical information processing in schizophrenia. Schizophr Bull 2005;31:117138. CrossRefGoogle Scholar
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edn. Washington DC: American Psychiatric Press, 1994. Google ScholarPubMed
Paxinos, G, Huang, X-F.Atlas of the human brainstem. San Diego: Academic Press, 1995. Google Scholar
Schmitz, C, Hof, PR.Design-based stereology in neuroscience. Neuroscience 2005;130:813831. CrossRefGoogle ScholarPubMed
Gundersen, HJ, Bagger, P, Bendtsen, TFet al. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Acta Pathol Microbiol Immunol Scand 1988;96:857881. CrossRefGoogle ScholarPubMed
Howard, CV, Reed, MG.Unbiased stereology. Oxford: Garland Science/BIOS Scientific Publishers, 2005. Google Scholar
Gundersen, HJG, Jensen, EBV.The efficiency of systematic sampling - reconsidered. J Microsc 1999;193:199211. CrossRefGoogle ScholarPubMed
Zahn, TP, Pickar, D.Autonomic activity in relation to symptom ratings and reaction time in unmedicated patients with schizophrenia. Schizophr Res 2005;79:257270. CrossRefGoogle ScholarPubMed
Danos, P, Schmidt, A, Baumann, Bet al. Volume and neuron number of the mediodorsal thalamic nucleus in schizophrenia: A replication study. Psychiatry Res Neuroimaging 2005;140:281289. CrossRefGoogle ScholarPubMed
Clinton, SM, Meador-Woodruff, JH.Thalamic dysfunction in schizophrenia: neurochemical, neuropathological, and in vivo imaging abnormalities. Schizophr Res 2004;69: 237253. CrossRefGoogle ScholarPubMed
Byne, W, Buchsbaum, MS, Mattiace, LAet al. Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. Am J Psychiatry 2002;159:5965. CrossRefGoogle ScholarPubMed
Roberts, RC, Roche, JK, Conley, RR.Synaptic differences in the patch matrix compartments of subjects with schizophrenia: A postmortem ultrastructural study of the striatum. Neurobiol Dis 2005;20:324335. CrossRefGoogle ScholarPubMed
Stark, AK, Uylings, HBM., Sanz-Arigita, E, Pakkenberg, B.Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry 2004;161:882888. CrossRefGoogle ScholarPubMed
Todtenkopf, MS, Vincent, SL, Benes, FM.A cross-study meta-analysis and three-dimensional comparison of cell counting in the anterior cingulate cortex of schizophrenic and bipolar brain. Schizophr Res 2005;73:7989. CrossRefGoogle ScholarPubMed
Cullen, TJ, Walker, MA, Eastwood, SL, Esiri, MM, Harrison, PJ, Crow, TJ.Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia. Br J Psychiatry 2006;188:2631. CrossRefGoogle Scholar
Pierri, JN, Volk, CLE, Auh, S, Sampson, A, Lewis, DA.Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia. Arch Gen Psychiatry 2001;58:466473. CrossRefGoogle ScholarPubMed
Casanova, MF, De Zeeuw, L, Switala, Aet al. Mean cell spacing abnormalities in the neocortex of patients with schizophrenia. Psychiatry Res 2005;133:112. CrossRefGoogle ScholarPubMed
Marner, L, Soborg, C, Pakkenberg, B.Increased volume of the pigmented neurons in the locus coeruleus of schizophrenic subjects. A stereological study. J Psychiatr Res 2005;39:337345. CrossRefGoogle ScholarPubMed
Craven, RM, Priddle, TH, Crow, TJ, Esiri, MM.The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurons. Neuropathol Appl Neurobiol 2005;31:115126. CrossRefGoogle Scholar
Craven, RM, Priddle, TH, Cooper, SJ, Crow, TJ, Esiri, MM.The dorsal raphe nucleus in schizophrenia: a post mortem study of 5-hydroxytryptamine neurones. Neuropathol Appl Neurobiol 2005;31:258269. CrossRefGoogle ScholarPubMed
Tandon, R, Greden, JF.Cholinergic hyperactivity and negative schizophrenic symptoms. Arch Gen Psychiatry 1989;46:745753. CrossRefGoogle ScholarPubMed
German, DC, Manaye, KF, Hersh, LB, Zweig, RM.Mesopontine cholinergic and non-cholinergic neurons in schizophrenia. Neuroscience 1999;94:3338. CrossRefGoogle Scholar
Garcia-Rill, E, Biedermann, JA, Chambers, Tet al. Mesopontine neurons in schizophrenia. Neuroscience 1995; 66:321335. CrossRefGoogle Scholar
Karson, CN, Mrak, RE, Husain, MM, Griffin, WS.Decreased mesopontine choline acetyltransferase levels in schizophrenia. Correlation with cognitive functions. Mol Chem Neuropathol 1996;29:181191. CrossRefGoogle Scholar
Konopaske, GT, Dorph-Petersen, KA, Pierri, JN, Wu, Q, Sampson, AR, Lewis, DA.Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of Macaque monkeys. Neuropsychopharmacology 2007;32:12161223. CrossRefGoogle ScholarPubMed
Cheng, G, Zhu, H, Zhou, X, Qu, J, Ashwell, KWS, Paxinos, G.Development of the human dorsal nucleus of the vagus. Early Hum Dev 2008;84:1527. CrossRefGoogle ScholarPubMed
Sase, M, Tamura, H, Ueda, K, Kato, H.Sonographic evaluation of antepartum development of fetal gastric motility. Ultrasound Obstet Gynecol 1999;13:323326. CrossRefGoogle ScholarPubMed
Sase, M, Miwa, I, Sumie, M, Nakata, M, Sugino, N, Ross, MG. Ontogeny of gastric emptying patterns in the human fetus. J Mater Fetal Neonatal Med 2005;17:213217. CrossRefGoogle Scholar
Allan, LD, Tynan, MJ, Campbell, S, Wilkinson, JL, Anderson, RH.Echocardiographic and anatomical correlates in the fetus. Br Heart J 1980;44:444451. CrossRefGoogle ScholarPubMed
Nyffeler, M, Meyer, U, Yee, BK, Feldon, J, Knuesel, I.Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: implications for schizophrenia. Neuroscience 2006;143:5162. CrossRefGoogle Scholar
Zhou, SY, Lu, YX, Yao, H, Owyang, C.Spatial organization of neurons in the dorsal motor nucleus of the vagus synapsing with intragastric cholinergic and nitric oxide/VIP neurons in the rat. Am J Physiol Gastrointest Liver Physiol 2008;294:G12011209. CrossRefGoogle ScholarPubMed
Bernstein, HG, Heinemann, A, Krell, D, Dobrowolny, H, Bielau, H, Keilhoff, G, Bogerts, B.Hypothalamic nitric oxide synthase in affective disorder: focus on the suprachiasmatic nucleus. Cell Mol Biol 2005;51:279284. Google ScholarPubMed
Karolewicz, B, Szebeni, K, Stockmeier, CAet al. Low nNOS protein in the locus coeruleus in major depression. J Neurochem 2004;91:10571066. CrossRefGoogle ScholarPubMed
Boettger, S, Hoyer, D, Falkenhahn, K, Kaatz, M, Yeragani, VK, Bär, KJ.Altered diurnal autonomic variation and reduced vagal information flow in acute schizophrenia. Clin Neurophysiol 2006;117:27152722. CrossRefGoogle ScholarPubMed
Malaspina, D, Bruder, G, Dalack, GWet al. Diminished cardiac vagal tone in schizophrenia: Associations to brain laterality and age of onset. Biol Psychiatry 1997;41:612617. CrossRefGoogle ScholarPubMed