Proton stress and calcium oxalate stress in schizophrenia, bipolar disorder and depression

Abstract

Despite intense efforts, the etiology of psychiatric disorders is not fully elucidated. Sequence features of examined causative factors for schizophrenia, bipolar disorder and depression are evident, including relatively high basic amino acid content, valine plus glycine content, and content of amino acids with hydrogen bonding capacities. These hallmarks, often more pronounced in segments of the causative proteins, give rise to stressful peptides prompting the buildup of chloride ion, the generation of acids, or/and the formation of insoluble and stiff calcium salts such as calcium oxalate or/and calcium phosphate. The sequence features of these risk factors allow the generation of potent hydrogen bonding and secondary chemical bonding to divalent cations, which can be intervened by non-proton monovalent cations as in the case of lithium carbonate. Weak anion carbonate can counteract strong anion chloride. The van der Waals radius of lithium is larger and smaller than that of proton and calcium respectively, endowing its competitiveness with protons and divalent cations. The weak acid valproate has been used in the treatment of bipolar disorder and schizophrenia, and it shares partial similarity in structure to glycine with a two-carbon backbone. The aforementioned biochemical insight will further our understanding on the pathogenesis of psychiatric disorders and open up new avenues in the search of clinically useful drugs.