Antipsychotic Drug Effects on Left Prefrontal Phospholipid Metabolism: A Follow-up 31P-2D-CSI Study of Haloperidol and Risperidone in Acutely Ill Chronic Schizophrenia Patients
Abstract
Introduction ³¹Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids.Methods We applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6 weeks, during which 7 patients were treated with haloperidol (10-16 mg/d) and 10 with risperidone (4-6 mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores.Results Follow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions.Conclusion Risperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Risperidone stimulates the remodeling of neuronal and synaptic phospholipids.
“Using this technique, the authors showed that risperidone stimulates the remodeling of neuronal and synaptic phospholipids.”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [139]
Cites
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090 · see citing works
The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia
GOFF, D. C., & Coyle, J. T. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.9.1367 · Cited by 914 · see citing works
Structured Clinical Interview for DSM-IV
(2007) · Sage eBooks · doi:10.4135/9781412952644.n443 · Cited by 725 · see citing works
Haro, J. M., Kamath, S., Ochoa, S., Novick, D., Rele, K., Fargas, A., Rodríguez, M. J., Rele, R., Orta, J., Kharbeng, A., et al. (2003) · Acta Psychiatrica Scandinavica · doi:10.1034/j.1600-0447.107.s416.5.x · Cited by 659 · see citing works
Metabolomic Mapping of Atypical Antipsychotic Effects in Schizophrenia
Kaddurah-Daouk, R., McEvoy, J., Baillie, R. A., Lee, D., Yao, J. K., Doraiswamy, P. M., & Krishnan, K. R. R. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002000 · Cited by 262 · see citing works
Effects of antipsychotics on brain structure
Scherk, H., & Falkai, P. (2006) · Current Opinion in Psychiatry · doi:10.1097/01.yco.0000214339.06507.d8 · Cited by 245 · see citing works
Christian Gaser, B. (2003) · Cerebral Cortex · doi:10.1093/cercor/bhg107 · Cited by 245 · see citing works
Millan, M. (2005) · Psychopharmacology · doi:10.1007/s00213-005-2199-1 · Cited by 226 · see citing works
Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings–part I
Stanley, J. A., Pettegrew, J. W., & Keshavan, M. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00949-5 · Cited by 202 · see citing works
Tayoshi, S., Nakataki, M., Sumitani, S., Taniguchi, K., Shibuya‐Tayoshi, S., Numata, S., Iga, J., Ueno, S., Harada, M., & Ohmori, T. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.11.011 · Cited by 113 · see citing works
GOFF, D. C., Hennen, J. A., Lyoo, I. K., Tsai, G. E., Wald, L. L., Evins, A. E., Yurgelun-Todd, D. A., & Renshaw, P. F. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01321-x · Cited by 101 · see citing works
Volz, H., Riehemann, S., Maurer, I., et al. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00235-3 · Cited by 96 · see citing works
Braus, D. F. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)00003-2 · Cited by 77 · see citing works
Bustillo, J., Rowland, L. M., Jung, R. E., Brooks, W. M., Qualls, C., Hammond, R., Hart, B. L., & Lauriello, J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301631 · Cited by 73 · see citing works
Szulc, A., Galińska-Skok, B., Tarasów, E., Dzienis, W., Kubas, B., Konarzewska, B., Walecki, J. M., Alathiaki, A. S., & Czernikiewicz, A. (2005) · Pharmacopsychiatry · doi:10.1055/s-2005-873156 · Cited by 72 · see citing works
Implications of lipid biology for the pathogenesis of schizophrenia
Berger, G. E., Wood, S. J., Pantelis, C., Velakoulis, D., Wellard, R. M., & McGorry, P. D. (2002) · Australian & New Zealand Journal of Psychiatry · doi:10.1046/j.1440-1614.2001.01021.x · Cited by 67 · see citing works
Ertuğrul, A., Salancı, B. V., Başar, K., Oğuz, K. K., Demir, B., Ergün, E. L., Şentürk, S., Erbaş, B., Cila, A., & Uluğ, B. (2009) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2009.04.007 · Cited by 67 · see citing works
Smesny, S., Rosburg, T., Nenadić, I., Fenk, K. P., Kunstmann, S., Rzanny, R., Volz, H., & Sauer, H. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.12.023 · Cited by 61 · see citing works
Self-citationBustillo, J., Lauriello, J., Rowland, L. M., Jung, R. E., Petropoulos, H., Hart, B. L., Blanchard, J. J., Keith, S. J., & Brooks, W. M. (2001) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(01)00102-0 · Cited by 59 · see citing works
Volz, H., Rzanny, R., Rössger, G., et al. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00061-4 · Cited by 57 · see citing works
Self-citationFocal changes in brain energy and phospholipid metabolism in first-episode schizophrenia
Jensen, J. E., Miller, J., Williamson, P., Neufeld, R. W. J., Menon, R. S., MALLA, A. K., Manchanda, R., Schaefer, B., Densmore, M., & Drost, D. J. (2004) · The British Journal of Psychiatry · doi:10.1192/bjp.184.5.409 · Cited by 53 · see citing works
Phospholipase A2 activity is associated with structural brain changes in schizophrenia
Smesny, S., Milleit, B., Nenadić, I., Preul, C., Kinder, D., Lasch, J., Willhardt, I., Sauer, H., & Christian Gaser, B. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.05.009 · Cited by 47 · see citing works
Self-citationAlves, I., Staneva, G., Tessier, C., Salgado, G. F., & Nuss, P. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2011.02.021 · Cited by 40 · see citing works
Haloperidol Improves Membrane Phospholipid Abnormalities in Temporal Lobes of Schizophrenic Patients
Fukuzako, H. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00050-0 · Cited by 38 · see citing works
Gangadhar, B. N., Jayakumar, P. N., Subbakrishna, D. K., Janakiramaiah, N., & Keshavan, M. S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.7.1304 · Cited by 36 · see citing works
Szulc, A., Galińska-Skok, B., Tarasów, E., Kubas, B., Dzienis, W., Konarzewska, B., Popławska, R., Tomczak, A. A., Czernikiewicz, A., & Walecki, J. M. (2007) · PubMed · Cited by 35 · see citing works
Fukuzako, H. (2001) · The World Journal of Biological Psychiatry · doi:10.3109/15622970109027496 · Cited by 32 · see citing works
Smesny, S., Kunstmann, C., Kunstmann, S., Willhardt, I., Lasch, J., Yotter, R. A., Proffitt, T., Kerr, M., Marculev, C., Milleit, B., et al. (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2010.541283 · Cited by 27 · see citing works
Self-citationThéberge, J., Al-Semaan, Y. M., Jensen, J. E., et al. (2004) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2004.08.001 · Cited by 22 · see citing works
Membrane phospholipid abnormalities of basal ganglia in never-treated schizophrenia
Jayakumar, P. N., Gangadhar, B. N., Subbakrishna, D. K., Janakiramaiah, N., Srinivas, J. S., & Keshavan, M. S. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01829-2 · Cited by 21 · see citing works
Oruch, R., Hodneland, E., Pryme, I. F., & Holmsen, H. (2009) · Journal of Chemical Biology · doi:10.1007/s12154-009-0018-6 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers
Zorkina, Y., Ushakova, V., Ochneva, A., Tsurina, A., Abramova, O., Savenkova, V., Goncharova, A., Alekseenko, I., Morozova, I., Riabinina, D., et al. (2024) · Metabolites · doi:10.3390/metabo14020080 · Cited by 36 · see citing works
- Authors
- Smesny, S., Langbein, K., Rzanny, R., Gussew, A., Burmeister, H. P., Reichenbach, J. R., & Sauer, H.
- Affiliations
- Jena University Hospital (DE)
- Corresponding author
- Smesny, Stefan
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 138
- Issue
- 2-3
- Pages
- 164-170
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2080859696
- Cited by
- 18
- References
- 32
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- antipsychotic drugs, haloperidol
- MeSH terms
- Adult, Basal Ganglia, Cerebellum, Cerebral Cortex, Female, Haloperidol, Humans, Male, Membrane Lipids, Middle Aged, Magnetic Resonance Spectroscopy, Phospholipids, Phosphorus Isotopes, Schizophrenia, Antipsychotic Agents, Risperidone, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review