[en] Background. Previous work suggests that individuals with schizophrenia display an altered homovanillic acid (HVA) response to metabolic stress. The present study replicated and extended this paradigm, including individuals with elevated genetic risk for schizophrenia. Method. Patients with psychosis (n = 50), non-psychotic first-degree relatives of patients with psychosis (n = 5 1) and controls without psychosis (n = 50) underwent, in randomized order, double-blind administration of placebo and the glucose analogue 2-deoxy-D-glucose (2DG), which induces a mild, transient clinical state of glucoprivation. Plasma HVA and cortisol were assessed twice before the start of the 2DG/placebo infusion (baseline values), as well as four times post infusion. Data were analysed using multi-level random regression techniques. Results. During the stress condition, significant increases in plasma HVA and cortisol were found. The increase in plasma HVA level during the stress condition was significantly stronger in patients than in controls, whereas this was not the case in relatives v. controls. The increase in plasma cortisol during the stress condition was significantly less in patients than controls, but no significant difference in the increase of plasma cortisol during stress was found in the comparison between relatives and controls. Conclusions. Patients with psychosis, but not their non-psychotic first-degree relatives, show an altered neurobiological response to metabolic stress, suggesting that this dysregulation is not a genetically transmitted vulnerability, but an illness-related effect, possibly reflecting acquired sensitization of neuroendocrine systems by repeated environmental stressors or repeated stimulation with agonistic drugs.
Disciplines :
Treatment & clinical psychology
Author, co-author :
Marcelis, Machteld; University of Maastricht > Department of Psychiatry and Neuropsychology
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Gielen, Jacques ; Université de Liège - ULiège > Chimie médicale
Delespaul, Philippe; University of Maastricht > Department of Psychiatry and Neuropsychology
Van Os, Jim; University of Maastricht > Department of Psychiatry and Neuropsychology
Language :
English
Title :
Abnormal response to metabolic stress in schizophrenia: marker of vulnerability or acquired sensitization?
Publication date :
August 2004
Journal title :
Psychological Medicine
ISSN :
0033-2917
eISSN :
1469-8978
Publisher :
Cambridge Univ Press, New York, United States - New York
Albus, M., Ackenheil, M., Engel, R. R. & Muller, F. (1982). Situational reactivity of autonomic functions in schizophrenic patients. Psychiatry Research 6, 361-370.
Amin, F., Davidson, M. & Davis, K. L. (1992). Honrovanillic acid measurement in clinical research: a review of methodology. Schizophenia Bulletin 18, 123-148.
Amin, F. & Friedhoff, A. J. (1997). Plasma HVA as a tool to investigate presynaptic brain dopaminergic activity. In Plasma Homovanillic Acid in Schizophrenia (ed. J. Friedhoff and F. Amin), pp. 1-16. American Psychiatric Press, Inc.: Washington, DC.
Amin, F., Hashmi, A., Stroe, A. E., Adebogun, O., Densmore, D. & Knott, P. J. (1998). Reproducibility of plasma catecholamine metabolites in normal subjects. Biological Psychiatry 43, 233-235.
Brake, W. G., Noel, M. B., Boksa, P. & Gratton, A. (1997). Influence of perinatal factors on the nucleus accumbens dopamine response to repeated stress during adulthood: an electrochemical study in the rat. Neuroscience 77, 1067-1076.
Breier, A. (1989). A. E. Bennett award paper. Experimental approaches to human stress research: assessment of neurobiological mechanisms of stress in volunteers and psychiatric patients. Biological Psychiatry 26, 438-462.
Breier, A. & Buchanan, R. W. (1992). The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients. Life Science 51, 1527-1534.
Breier, A., Davis, O. R. & Buchanan, R. W. (1991). Alprazolam attenuates metabolic stress-induced neuroendocrine and behavioral effects in humans. Psychopharmacology 104, 479-484.
Breier, A., Davis, O. R., Buchanan, R. W., Moricle, L. A. & Munson, R. C. (1993). Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Archives of General Psychiatry 50, 541-550.
Breier, A., Wolkowitz, O. M., Doran, A. R., Bellar, S. & Pickar, D. (1988). Neurobiological effects of lumbar puncture stress in psychiatric patients and healthy volunteers. Psychiatry Research 25, 187-194.
Cannon, T. D., Mednick, S. A., Parnas, J., Schulsinger, F., Praestholm, J. & Vestergaard, A. (1993). Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors. Archives of General Psychiatry 50, 551-564.
Cannon, T. D., Van Erp, T. G., Huttunen, M., Lonnqvist, J., Salonen, O., Valanne, L., Poutanen, V. P., Standertskjold-Nordenstam, C. G., Gur, R. E. & Yan, M. (1998). Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. Archives of General Psychiatry 55, 1084-1091.
Cannon, T. D., Zorrilla, L. E., Shtasel, D., Gur, R. E., Gur, R. C., Marco, E.J., Moberg, P. & Price, R.A. (1994). Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers. Archives of General Psychiatry 51, 651-661.
Cardno, A. G., Jones, L. A., Murphy, K. C., Sanders, R. D., Asherson, P., Owen, M. J. & McGuffin, P. (1999). Dimensions of psychosis in affected sibling pairs. Schizophrenia Bulletin 25, 841-850.
Davila, R., Manero, E., Zumarraga, M., Andia, I., Schweitzer, J. W. & Friedhoff, A. J. (1988). Plasma homovanillic acid as a predictor of response to neuroleptics. Archives of General Psychiatry 45, 564-567.
Elman, I., Adler, C. M., Malhotra, A. K., Bir, C., Pickar, D. & Breier, A. (1998). Effect of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia. American Journal of Psychiatry 155, 979-981.
Elman, I., Sokoloff, L., Adler, C. M., Weisenfeld, N. & Breier, A. (1999). The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy Volunteers. Brain Research 815, 243-249.
Glenthoj, B. Y. & Hemmingsen, R. (1997). Dopaminergic sensitization: implications for the pathogenesis of schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 21, 23-46.
Goldstein, H. (1987). Multilevel Models in Educational and Social Research. Griffin: London.
Jansen, L. M., Gispen-de Wied, C. C., Gademan, P. J., De Jonge, R. C., van der Linden, J. A. & Kahn, R. S. (1998). Blunted cortisol response to a psychosocial stressor in schizophrenia. Schizophrenia Research 33, 87-94.
Jansen, L. M., Gispen-de Wied, C. C. & Kahn, R. S. (2000). Selective impairments in the stress response in schizophrenic patients. Psychopharmacology (Berlin) 149, 319-325.
Kapur, S. (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 13-23.
Kay, S. R., Fiszbein, A. & Opler, L.A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261-276.
Kay, S. R., Opler, L. A. & Lindenmayer, J. P. (1988). Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Research 23, 99-110.
Kendler, K. S. & Eaves, L. J. (1986). Models for the joint effect of genotype and environment on liability to psychiatric illness. American Journal of Psychiatry 143, 279-289.
Kendler, K. S., Neale, M., Kessler, R., Heath, A. & Eaves, L. (1993). A twin study of recent life events and difficulties. Archives of General Psychiatry 50, 789-796.
Kety, S. S., Wender, P. H., Jacobsen, B., Ingraham, L. J., Jansson, L., Faber, B. & Kinney, D. K. (1994). Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark. Archives of General Psychiatry, 51, 442-455.
Kopin, I.J., Bankiewicz, K.S. & Harvey-White, J. (1988). Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP. Neuropsychopharmacology 1, 119-125.
Krabbendam, L., Marcelis, M., Delespaul, P., Jolles, J. & van Os, J. (2001). Single or Multiple familial cognitive risk factors in schizophrenia? American Journal of Medical Genetics 105, 183-188.
Lukoff, D., Nuechterlein, K. H. & Ventura, J. (1986). Manual For the Expanded Brief Psychiatric Rating Scale. Schizophrenia Bulletin 12, 594-602.
Maas, J. W., Contreras, S. A., Seleshi, E. & Bowden, C. L. (1988). Dopamine metabolism and disposition in schizophrenic patients: studies using debrisoquin sulfate. Archives of General Psychiatry 45, 553-559.
McGuffin, P., Farmer, A. & Harvey, I. (1991). A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Archives of General Psychiatry 48, 764-770.
Meador-Woodruff, J. H. & Greden, J. F. (1988). Effects of psychotropic medications on hypothalamic-pituitary-adrenal regulation. Endocrinology and Metabolism Clinics of North America 17, 225-234.
Miller, A. L., True, J. E., Funderburg, L. & Maas, J. W. (1997). Methodological issues in interpreting plasma HVA levels in studies of schizophrenia. In plasma Homovanillic Acid in Schizophrenia (ed. J. Friedhoff and F. Amin), pp. 1-16. American Psychiatric Press, Inc.: Washington, DC.
Myin-Germeys, I., Krabbendam, L., Jolles, J., Delespaul, P. A. & van Os, J. (2002). Are cognitive impairments associated with sensitivity to stress in schizophrenia? An experience sampling study. American Journal of Psychiatry 159, 443-449.
Pickar, D., Wolkowitz, O. M., Labarca, R., Doran, A. R., Breier, A. & Paul, S. M. (1987). Biochemical alterations produced by neuroleptics in man: Studies of plasma homovanillic acid in schizophrenic patients. Psychopharmacology Series 3, 248-254.
Pickar, D., Breier, A. & Kelsoe, J. (1988). Plasma homovanillic acid as an index of central dopaminergic activity: studies in schizophrenic patients. Annals of the New York Academy of Sciences 537, 339-346.
Sharma, R., Javaid, J. I., Janicak, P., Faull, K., Comaty, J. & Davis, J.M. (1989). Plasma and CSF HVA before and after pharmacological treatment. Psychiatry Research 28, 97-104.
Sharma, T., du Boulay, G., Lewis, S., Sigmundsson, T., Gurling, H. & Murray, R. (1997). The Maudsley Family Study. I. Structural brain changes on magnetic resonance imaging in familial schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 21, 1297-1315.
Siever, L. J., Amin, F., Coccaro, E. F., Bernstein, D., Kavoussi, R. J., Kallus, O., Horvath, T. B., Warne, P., Davidson, M. & Davis, K. L. (1991). Plasma homovanillic acid in schizotypal personality disorder. American Journal of Psychiatry 148, 1246-1248.
Siever, L. J., Amin, F., Coccaro, E. F., Trestman, R., Silverman, J., Horvath, T. B., Mahon, T. R., Knott, P., Altstiel, L., Davidson, M., et al. (1993). CSF homovanillic acid in schizotypal personality disorder. American Journal of Psychiatry 150, 149-151.
Spitzer, R. L., Endicott, J. & Robbins, E. (1978). Research Diagnostic Criteria (RDC) for a Selected Group of Functional Psychoses. Biometrics Research Division, New York State Psychiatric Institute: New York.
StataCorp (2001). STATA Statistical Software: Release 8.0. College Station, TX.
Tienari, P., Sorri, A., Lahti, I., Naarala, M., Wahlberg, K. E., Ronkko, T., Pohjola, J. & Moring, J. (1985). The Finnish adoptive family study of schizophrenia. Yale Journal of Biology and Medicine 58, 227-237.
Ujike, H. (2002). Stimulant-induced psychosis and schizophrenia: the role of sensitization. Current Psychiatry Reports 4, 177-184.
Van Os, J. & Sham, P. (2002). Gene-environment interactions. In The Epidemiology of Schizophrenia (ed. R. M. Murray, P. B. Jones, E. Susser, J. Van Os and M. Cannon), pp. 235-254. Cambridge University Press: Cambridge, UK.
Welle, S. L., Thompson, D. A., Campbell, R. G. & Lilavivathana, U. (1980). Increased hunger and thirst during glucoprivation in humans. Physiology & Behavior 25, 397-403.
Yoshimatsu, H., Oomura, Y., Katafuchi, T. & Niijima, A. (1987). Effects of hypothalamic stimulation and lesion on adrenal nerve activity. American Journal of Physiology 253, 418-424.
Zubin, J. & Spring, B. (1977). Vulnerability: a new view of schizophrenia. Journal of Abnormal Psychology 86, 103-126.