Carbonyl stress and schizophrenia

• Published in: Psychiatry and clinical neurosciences 2014-09, Vol.68 (9), p.655-665
• Main Authors: Arai, Makoto, Miyashita, Mitsuhiro, Kobori, Akiko, Toriumi, Kazuya, Horiuchi, Yasue, Itokawa, Masanari
• Format: Article
• Language: English
• Subjects: advanced glycation end products; Arginine - analogs & derivatives; Arginine - blood; Biomarkers - blood; Drug therapy; Glycation End Products, Advanced - metabolism; glyoxalase; Humans; Lactoylglutathione Lyase - genetics; Lactoylglutathione Lyase - metabolism; Lysine - analogs & derivatives; Lysine - blood; Mutation; pentosidine; Psychiatric Status Rating Scales; pyridoxal; Pyridoxal - blood; Pyridoxamine - therapeutic use; Schizophrenia; Schizophrenia - blood; Schizophrenia - classification; Schizophrenia - drug therapy; Schizophrenia - metabolism; Stress, Physiological; vitamin B6
• ISSN: 1323-1316; 1440-1819
• DOI: 10.1111/pcn.12216

Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although schizophrenia's positive symptoms are largely managed through treatment with atypical antipsychotics, new classes of drugs are needed to address the unmet medical need for improving cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of proteins and the formation of advanced glycation end products, such as pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of schizophrenia patients, leading to a failure of metabolic systems with plasma pentosidine accumulation and serum pyridoxal depletion. Our findings suggest two markers, pentosidine and pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in schizophrenia. Here, we define a subtype of schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a biomarker in the challenge of overcoming heterogeneity in schizophrenia treatment.