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Original Investigation

Familial abnormalities of endocannabinoid signaling in schizophrenia

Dagmar KoetheBrain and Mind Centre, The University of Sydney, Sydney, Australia; ;Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;

http://orcid.org/0000-0002-8324-6756 View further author information

Franziska PahlischDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; ;Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA;

http://orcid.org/0000-0003-0167-3832 View further author information

Martin HellmichInstitute for Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany;

http://orcid.org/0000-0001-5174-928X View further author information

Cathrin RohlederDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;

http://orcid.org/0000-0002-3559-1846 View further author information

Juliane K. MuellerDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; View further author information

Andreas Meyer-LindenbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;

http://orcid.org/0000-0001-5619-1123 View further author information

E. Fuller TorreyThe Stanley Medical Research Institute, Bethesda, MD, USAView further author information

Daniele PiomelliDepartment of Anatomy and Neurobiology, University of California, Irvine, CA, USA;

http://orcid.org/0000-0002-2983-774X View further author information

F. Markus LewekeBrain and Mind Centre, The University of Sydney, Sydney, Australia; ;Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Correspondence[email protected]

http://orcid.org/0000-0002-8163-195X View further author information

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Abstract

Objectives: Epidemiological and experimental evidence suggests that the endocannabinoid system plays a pathophysiological role in schizophrenia. This is reflected by elevated cerebrospinal levels of the endocannabinoid anandamide in schizophrenia and its initial prodromal states.

Methods: We analyzed plasma concentrations of anandamide, 2-arachidonoyl-sn-glycerol, palmitoylethanolamide and oleoylethanolamide from 25 twin pairs discordant for schizophrenia, six discordant for bipolar disorder and eight healthy twin pairs to determine hereditary traits.

Results: Twin pairs discordant for schizophrenia or bipolar disorder had significantly higher levels of anandamide and palmitoylethanolamide compared to healthy twins (both P < 0.002). Non-affected twins discordant for schizophrenia, who developed a psychotic disorder within 5 years follow-up showed lower anandamide (P = 0.042) and 2-arachidonoyl-sn-glycerol levels (P = 0.049) than twins who remained healthy.

Conclusions: We suggest that the protective upregulation of endocannabinoid signalling reflects either a hereditary trait or mirrors a modulating response to genetically influenced cerebral function involving, e.g., other neurotransmitters or energy metabolism.

Keywords:

Acknowledgements

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Statement of interest

All authors declare that they have no conflicts of interest. AML discloses speaker and/or advisor or authorship fees from Astra Zeneca, Servier, Bristol-Myers Squibb GmbH & Co.KGaA, Desitin Arzneimittel GmbH, Defined Health, F. Hoffmann-La Roche Ltd., Lilly Deutschland GmbH, Gerson Lehrmann Group (GLG), Pricespective, Elsevier, Alexza Pharmaceuticals Inc., Outcome Sciences Inc., Pfizer Pharma GmbH, Janssen-Cilag EMEA. FML discloses speaker and/or advisor or authorship fees from Astra Zeneca, Bristol-Myers Squibb GmbH & Co. KGaA, Essex Pharma GmbH, Exafield, Future Science Group, Lilly Research Laboratories, Lundbeck GmbH, Medical Tribune, Neuro Depesche. He is a shareholder of Curantis UG (Ltd.). All other authors have nothing to declare.

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Funding

The study was funded by the Stanley Medical Research Institute (01-315 and 03-NV-003 to FML), and the Koeln Fortune Program (108-2000 and 136-2007 to FML).

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Familial abnormalities of endocannabinoid signaling in schizophrenia

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Familial abnormalities of endocannabinoid signaling in schizophrenia

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