Idiopathic carbonyl stress in a drug-naive case of at-risk mental state
Article first published online: 17 OCT 2011
© 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences
Volume 65, Issue 6, pages 606–607, October 2011
How to Cite
Arai, M., Koike, S., Oshima, N., Takizawa, R., Araki, T., Miyashita, M., Nishida, A., Miyata, T., Kasai, K. and Itokawa, M. (2011), Idiopathic carbonyl stress in a drug-naive case of at-risk mental state. Psychiatry and Clinical Neurosciences, 65: 606–607. doi: 10.1111/j.1440-1819.2011.02261.x
- Issue published online: 17 OCT 2011
- Article first published online: 17 OCT 2011
- Received 27 April 2011; revised 7 July 2011; accepted 8 August 2011.
WE PREVIOUSLY REPORTED that a subgroup of schizophrenia patients exhibit carbonyl stress with high plasma pentosidine levels, without underlying diabetes mellitus or chronic kidney disease, the two major causes of elevated, advanced glycation end-products.1 These patients, however, had previously received antipsychotic therapy, leaving the possible role of medication in carbonyl stress unclear. Here, we report on a drug-naive patient with at-risk mental state (ARMS), who exhibited enhanced carbonyl stress with high plasma pentosidine levels.
The patient was a 21-year-old male college student, who was born at full term after an uneventful pregnancy and delivery. He first developed obsessive thoughts at age 18 and sought medical help because of communication difficulties and depression. He was diagnosed with obsessive and compulsive disorder (OCD) according to DSM-IV criteria. Biweekly counseling and psychotherapy temporarily reduced his symptoms but a persistence of confused thoughts, hearing hypersensitivity and delusional ideation of persecution and reference led to a diagnosis of ARMS, according to Structured Interview for Prodromal Syndromes (SIPS) criteria, 10 months after his initial consultation. He was followed clinically for 12 months and treated temporarily with 0.5 mg of etizolam and 5 mg of zolpidem, which improved his symptoms. He entered a research study on ARMS and his symptoms were scaled and biochemical data measured at his initial visit, and also after 16 months of treatment. During this period his score on the Positive and Negative Syndrome Scale decreased from 84 to 58 (P = 0.001), his positive subscale score changed from 20 to 22 (P = 0.38), negative subscale score changed from 22 to 9 (P = 0.03) and the general psychopathology subscale score changed from 42 to 27 (P = 0.008). Global Assessment of Functioning also improved from 55 to 65. Plasma pentosidine levels decreased from 113.2 to 44.1 ng/mL. We did not measure carbonyl compounds such as methylglyoxal (MG), carbohydrate precursors of pentosidine and advanced glycation adducts: N(ε)-(carboxymethyl)lysine and N(ε)-(carboxyethyl)lysine. We did not assess the activity of glyoxalase1 (GLO1) or pyridoxal levels before treatment, but after treatment the activity was 7.55 mU/106 red blood cells, and the pyridoxal level was 6.8 ng/mL, and these are both normal levels for the enzyme and pyridoxal, respectively. It is not known whether etizolam and zolpidem affect pentosidine levels. In the preliminary data, the dose (mg/day) of etizolam (n = 18) or zolpidem (n = 11) was not significantly correlated with pentosidine levels in patients with schizophrenia (data not shown). The patients were also taking other drugs, however, and thus the lack of apparent correlation is not conclusive. The GLO1 genotype in the present case was wild type (c.332A>C, p.Glu111/Glu111). Biochemistry did not demonstrate any abnormalities indicative of disease, such as diabetes mellitus or chronic kidney diseases.
The present case report does not demonstrate a direct link between carbonyl stress and the disease development. It is not known whether carbonyl stress is a cause or consequence of the disease. In addition, it cannot be ruled out that other physical conditions or drugs affected the pentosidine levels. Additional data are needed to clarify a possible relationship between carbonyl stress and mental disorders.
The ethics committees for the University of Tokyo and Tokyo Institute of Medical Science approved the present study (2089-(2), 2094-(2), 2226-(1), 21–2). The subject gave written informed consent in accordance with the Declaration of Helsinki after a complete explanation of the original study. After ethics approval, the patient re-consented for publication of this case report.
This study was supported by grants from the Ministry of Health, Labour, and Welfare (H22-seishin-ippan-015 to KK), and from the JSPS/MEXT (No. 21249064 and Grant-in-Aid for Scientific Research on Innovative Areas [Comprehensive Brain Science Network] to KK, No. 20249054 and Grant-in-Aid for Scientific Research (A), no. 22129007 and Grant-in-Aid for Scientific Research on Priority Areas to MI). A part of this study was also the result of ‘Development of biomarker candidates for social behavior’ carried out under the Strategic Research Program for Brain Sciences by MEXT.