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A Hypothesis Concerning Schizophrenia

Clinical and Experimental Psychology

Opinion Article - (2016) Volume 2, Issue 3

A Hypothesis Concerning Schizophrenia

Theresa Hannon BA Hons*
Open University UK, UK
*Corresponding Author: Theresa Hannon BA Hons, Department of Psychology, Open University UK, 31 Meadowbank Street, Belfast, N.I. BT9 7FG, UK, Tel: + 007411748477 Email:

Abstract

In 1965, Bell noted that amphetamine psychosis mimicked schizophrenia. Later, van Ree and Otte  lucidated that amphetamine and alpha-endorphin had similar effects  in the Central Nervous System, while Wiegant et al. found increased levels of gamma and alpha-endorphin in the hypothalamic tissue of schizophrenic human cadavers.

Opinion

In 1965, Bell noted that amphetamine psychosis mimicked schizophrenia [1]. Later, van Ree and Otte [2] elucidated that amphetamine and alpha-endorphin had similar effects [2] in the Central Nervous System, while Wiegant et al. [3] found increased levels of gamma and alpha-endorphin in the hypothalamic tissue of schizophrenic human cadavers [3].

Theresa Hannon’s suggestion is that this endogeneous alphaendorphin isn’t degraded, and so tends to pile up in the CNS; an analysis of alpha-endorphin’s role in the endorphin metabolic pathway is provided by Burbach et al. [4].

The aminopeptidase responsible for degrading alpha-endorphin in the CNS has been identified as Aminopeptidase N (also known as CD13 and Alanyl (Membrane) Aminopeptidase); Hannon suspects that this enzyme is miscoded in the case of schizophrenics, such that it fails to degrade alpha-endorphin. A human alpha-endorphin ELISA Assay which may reveal the resulting excess of alpha-endorphin is suggested [5].

The perceptive reader may be wondering why Hannon has selected the human gene ‘ANPEP’ for detailed study; the reason is that ANPEP codes for Alanyl (Membrane) Aminopeptidase in humans. Interestingly, ANPEP exists as more than one isoform: Hannon would argue that the first isoform is expressed in childhood and another isoform is expressed from adolescence onwards. Childhood Schizophrenia might be explained by a defect common to both isoforms (alternatively spliced over time), while Adolescence-Onset Schizophrenia might be explained by miscoding of the second (later) isoform. In humans, ANPEP is located on Chromosome 15; its NCBI Accession Number is NC_000015.10, and its range is 89784895..89814854.

CD13 isn’t just expressed on CNS synaptosomes but is also present on the plasma membrane of skin fibroblasts [6]. This would indicate that defects in ANPEP could be characterized by ordinary skin fibroblast biopsies (taken from children and adults). Human ANPEP mRNA has been sequenced; its NCBI Accession Number is NM_001150.2. This has been mentioned as Lorenz et al have noted in 2011 that cells can ingest mRNA and translate it (to some extent) into working protein [7].

An animal model of Schizophrenia exists: namely, mad dogs. Intravenous injection of this mRNA into these animals should correct their (canine) psychosis- although (as NM_001150.2 codes for a human protein) there would be a risk of an immune response. Correction of canine psychosis should provide evidence that NM_001150.2 ought to correct Human Schizophrenia.

References

  1. Bell DS (1965) Comparison of Amphetamine Psychosis and Schizophrenia. Br J Psychiatry111:701-7.
  2. Van Ree JM, Otte AP (1980) Effects of (des-tyr1)-y-endorphin and alpha-endorphin as compared to haloperidol and amphetamine on nucleus accumbens self-stimulation. Neuropharmacol19:429P-34.
  3. Wiegant VM, Verhoef CJ, Burbach JP, de Wied D (1988) Increased concentration of alpha- and gamma-endorphin in post mortem hypothalamic tissue of schizophrenic patients. Life Sci42:1733-42.
  4. Burbach J, de Kloet E, Schotman P, de Wied D (1981) Proteolytic conversion of beta-endorphin by brain synaptic membranes. J Biol Chem256:12463-9.
  5. Bordessoule D, Jones M, Gatter KC, Mason DY (1993) Immunohistological patterns of myeloid antigens: tissue distribution of CD13, CD14, CD16, CD31, CD36, CD65, CD66 and CD67. Br J Haematol 83: 370-83.
  6. Lorenz C, Fotin-Mieczec M, Roth G, Becker C, Dam T, et al. (2011) Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway. RNA Biol 8: 627-36.
Citation: Hons THBA (2016) A Hypothesis Concerning Schizophrenia. Clin Exp Psychol 2:134.

Copyright: © 2016 Hons THBA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.