Download PDF
Pharmacopsychiatry 2005; 38(5): 214-219
DOI: 10.1055/s-2005-873156
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Risperidone on Metabolite Measures in the Frontal Lobe, Temporal Lobe, and Thalamus in Schizophrenic Patients. A Proton Magnetic Resonance Spectroscopy (1H MRS) Study

A. Szulc1 , B. Galinska1 , E. Tarasow2 , W. Dzienis2 , B. Kubas2 , B. Konarzewska1 , J. Walecki3 , A. S. Alathiaki2 , A. Czernikiewicz1
  • 1Department of Psychiatry, Medical University in Bialystok, Bialystok, Poland
  • 2Department of Radiology, Medical University in Bialystok, Bialystok, Poland
  • 3Polish Academy of Sciences, Warsaw, Poland
Further Information

Publication History

Received: 10.2.2005 Revised: 9.5.2005

Accepted: 6.7.2005

Publication Date:
27 September 2005 (online)

Also available at
    Permissions and Reprints

Objective: The aim of the study was the evaluation of risperidone effect on metabolite measures in the frontal lobe, temporal lobe and thalamus in schizophrenic patients on the basis of proton magnetic resonance spectroscopy (1H MRS). Methods: A group of 14 patients with the diagnosis of schizophrenia, according to DSM-IV, were examined in the study. The patients were examined twice, once after a period of at least 7 days without neuroleptics and for the second time at least 4 weeks after stable risperidone doses. Results: The significant differences in the metabolite levels before and after the treatment were observed only in thalamus: an increase in myoinositol (mI) and N-acetylaspartate (NAA) levels. Positive symptoms before the treatment correlated positively with NAA level in the frontal lobes and negatively in the temporal lobes. Negative symptoms before the treatment correlated positively with Glx (a common signal for GABA, glutamine and glutamate) level in the temporal lobes. Conclusion: Our results seem to confirm the influence of risperidone on the brain metabolism, specifically in the region of thalamus.

References

  • 1 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, International Version. Washington, DC; American Psychiatric Association 1995
    Search in Google Scholar
  • 2 Andreasen N C, Paradiso S, O’Leary D S. ”Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry?.  Schizophr Bull. 1998;  24 203-218
    CrossrefPubMedSearch in Google Scholar
  • 3 Bartha R, Al-Semaan Y M, Williamson P C, Drost D J, Malla A K, Carr T J. et al . A short proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients.  Biol Psychiatry. 1999;  45 1403-1411
    CrossrefPubMedSearch in Google Scholar
  • 4 Bartha R, Williamson P C, Drost D J, Malla A, Carr T J, Cortese L. et al . Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy.  Arch Gen Psychiatry. 1997;  54 959-965
    CrossrefPubMedSearch in Google Scholar
  • 5 Berger G E, Wood S J, Wellard M, Proffitt M T, McConchie M, Pantelis C. et al . In vivo brain imaging and implications for neuroprotection in early psychosis.  World J Biol Psychiatry. 2004;  5 (Suppl 1) 20
    PubMedSearch in Google Scholar
  • 6 Bertolino A, Callicott J H, Mattay V S, Weidenhammer K M, Rakow R, Egan M F. et al . The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia.  Biol Psychiatry. 2001;  49 39-46
    CrossrefPubMedSearch in Google Scholar
  • 7 Bertolino A, Esposito G, Callicott J H, Mattay V S, Van Horn J D, Frank J A. et al . Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia.  Am J Psychiatry. 2000;  157 26-33
    PubMedSearch in Google Scholar
  • 8 Bertolino A, Sciota D, Brudaglio F, Altamura M, Blasi G, Bellomo A. et al . Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder.  Am J Psychiatry. 2003;  160 483-489
    CrossrefPubMedSearch in Google Scholar
  • 9 Bustillo J R, Lauriello J, Rowland L M, Thomson L M, Petropoulos H, Hammond R. et al . Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure.  Schizophr Res. 2002;  58 313-321
    CrossrefPubMedSearch in Google Scholar
  • 10 Bustillo J, Wolff C, Myers-y-Guterrez A, Dettmer T S, Cooper T B, Allan A. et al . Treatment of rats with antipsychotic drugs: lack of an effect on brain N-acetylaspartate levels.  Schizophr Res. 2004;  66 31-39
    CrossrefPubMedSearch in Google Scholar
  • 11 Callicott J H, Bertolino A, Egan M F, Mattay V S, Langheim F JP, Weinberger D R. Selective relationship between prefrontal N-acetylaspartate measures and negative smptoms in schizophrenia.  Am J Psychiatry. 2000;  157 1646-1651
    CrossrefPubMedSearch in Google Scholar
  • 12 Cecil K M, Lenkinski R E, Gur R E, Gur R C. Proton magnetic resonance spectroscopy in the frontal and temporal lobes of neuroleptic naive patients with schizophrenia.  Neuropsychopharmacology. 1999;  20 131-140
    CrossrefPubMedSearch in Google Scholar
  • 13 Choe B -Y, Suh T -S, Shinn K -S, Lee C -W, Lee C, Paik I -H. Observation of metabolic changes in chronic schizophrenia after neuroleptic treatment by in vivo hydrogen magnetic resonance spectroscopy.  Invest Radiol. 1996;  31 345-352
    CrossrefPubMedSearch in Google Scholar
  • 14 Deicken R F, Johnson C, Eliaz Y, Schuff N. Reduced concentrations of thalamic N-acetylaspartate in male patients with schizophrenia.  Am J Psychiatry. 2000;  157 644-647
    CrossrefPubMedSearch in Google Scholar
  • 15 Deicken R F, Zhou L, Corwin F, Vinogradov S, Weiner M W. Decreased left frontal lobe N-acetylaspartate in schizophrenia.  Am J Psychiatry. 1997;  154 688-690
    PubMedSearch in Google Scholar
  • 16 Deicken R F, Zhou L, Schuff N, Fein G, Weiner M W. Hippocampal neuronal dysfunction in schizophrenia as measured by proton magnetic resonance spectroscopy.  Biol Psychiatry. 1998;  43 483-488
    CrossrefPubMedSearch in Google Scholar
  • 17 Delamillieure P, Fernandez J, Constans J -M, Brazo P, Benali K, Abadie P. et al . Proton magnetic resonance spectroscopy of the medial prefrontal cortex in patients with deficit schizophrenia: preliminary report.  Am J Psychiatry. 2000;  157 641-643
    CrossrefPubMedSearch in Google Scholar
  • 18 Ende G, Braus D F, Walter S, Weber-Fahr W, Henn F A. Multiregional 1H-MRSI of the hippocampus, thalamus, and basal ganglia in schizophrenia.  Eur Arch Psychiatry Clin Neurosci. 2003;  253 9-15
    CrossrefPubMedSearch in Google Scholar
  • 19 Fannon D, Simmons A, Tennakoon L, O’Céallaigh S, Sumich A, Doku V. et al . Selective deficit of hippocampal N-acetyaspartate in antipsychotic-naive patients with schizophrenia.  Biol Psychiatry. 2003;  54 587-598
    CrossrefPubMedSearch in Google Scholar
  • 20 Fukuzako H, Kodama S, Fukuzako T, Yamada K, Doi W, Sato D. et al . Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy.  Psychiatry Res Neuroimaging. 1999;  92 45-56
    CrossrefPubMedSearch in Google Scholar
  • 21 Goff  D C, Hennen J, Lyoo I K, Tsai G, Wald L L, Evins A E. et al . Modulation of Brain and serum Glutamatergic concentrations Following a switch from Conventional Neuroleptics to Olanzapine.  Biol Psychiatry. 2002;  51 493-497
    CrossrefPubMedSearch in Google Scholar
  • 22 Heimberg C, Komoroski R A, Lawson W B, Cardwell D, Karson C E. Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect.  Psychiatry Res Neuroimaging. 1998;  83 105-115
    PubMedSearch in Google Scholar
  • 23 Jones R S, Waldman A D. 1H-MRS evaluation of metabolism in Alzheimer’s disease and vascular dementia.  Neurol Res. 2004;  26 488-495
    CrossrefPubMedSearch in Google Scholar
  • 24 Kay S R, Fiszbein A, Opler L A. The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia.  Schizophr Bull. 1987;  13 261-276
    CrossrefPubMedSearch in Google Scholar
  • 25 Kantarci K, Petersen R C, Boeve B F, Knopman D S, Tang-Wai D F, O’Brien P C. et al . 1H MRS spectroscopy in common dementias.  Neurology. 2004;  63 1393-1398
    CrossrefPubMedSearch in Google Scholar
  • 26 Keshavan M S, Stanley J A, Pettegrew J W. Magnetic Resonance Spectroscopy in Schizophrenia: Methodological Issues and Findings-Part II.  Biol Psychiatry. 2000;  48 369-80
    Search in Google Scholar
  • 27 Miyaoka T, Yasukawa R, Mizuno S, Sukegawa T, Inagaki T, Horiguo Seno H. et al . Proton magnetic resonance spectroscopy (1H MRS) of hippocampus, basal ganglia, and vermis of cerebellum in schizophrenia associated with idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome).  J Psychiatr Res. 2005;  39 29-34
    CrossrefPubMedSearch in Google Scholar
  • 28 Lindquist DM Hawk R M, Karson C R, Komoroski R A. Effects of Antipsychotic Drugs on Metabolite Ratios i Rat Brain in Vivo.  Magn Reson Med. 2000;  43 355-358
    CrossrefPubMedSearch in Google Scholar
  • 29 Pae C U, Choe B Y, Joo R H, Lim H K, Kim T S, Too S S. Neuronal dysfunction of the frontal lobe in schizophrenia.  Neuropsychobiology. 2004;  50 211-215
    CrossrefPubMedSearch in Google Scholar
  • 30 Sigmundsson T, Maier M, Toone B K, Williams S CR, Simmons A, Greenwood K. et al . Frontal lobe N-acetyaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study.  Schizophr Res. 2003;  64 63-71
    CrossrefPubMedSearch in Google Scholar
  • 31 Stanley J A, Williamson P C, Drost D J, Rylett R J, Carr T J, Malla A. et al . An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients.  Schizophr Bull. 1996;  22 597-609
    PubMedSearch in Google Scholar
  • 32 Stanley J A. Magnetic Resonance Spectroscopy in Schizophrenia: Methodological Issues and Findings-Part I.  Biol Psychiatry. 2000;  48 357-368
    CrossrefPubMedSearch in Google Scholar
  • 33 Tebartz van Elst L, Baumer D, Ebert D, Trimble M R. Chronic Antidopaminergic Medication Might Affect Amygdala Structure in Patients with Schizophrenia.  Pharmacopsychiatry. 2004;  37 217-220
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Théberge J, Al-Semaan Y, Williamson P C, Menon R S, Neufeld R W, Rajakumar N. et al . Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS.  Am J Psychiatry. 2003;  160 2231-2233
    CrossrefPubMedSearch in Google Scholar
  • 35 Théberge J, Bartha R, Drost D J, Menon R S, Malla A, Takhar J. et al . Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers.  Am J Psychiatry. 2002;  159 1944-1946
    CrossrefPubMedSearch in Google Scholar

Dr. Agata Szulc

Department of Psychiatry

Medical University in Bialystok

16-070 Choroszcz, Pl. Brodowicza 1

Poland

Phone: +48 85 7193979

Fax: +48 85 7193978

Email: agataszulc@poczta.onet.pl