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BMC Psychiatry
Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Research article

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study

Authors: Kazuo Takiguchi, Akihito Uezato, Michio Itasaka, Hidenori Atsuta, Kenji Narushima, Naoki Yamamoto, Akeo Kurumaji, Makoto Tomita, Kazunari Oshima, Kosaku Shoda, Mai Tamaru, Masahito Nakataki, Mitsutoshi Okazaki, Sayuri Ishiwata, Yasuyoshi Ishiwata, Masato Yasuhara, Kunimasa Arima, Tetsuro Ohmori, Toru Nishikawa

Published in: BMC Psychiatry | Issue 1/2017

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Abstract

Background

It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs.

Methods

We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales.

Results

D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower.

Conclusion

It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity.

Trial registration

UMIN Clinical Trials Registry (number UMIN000000468). Registered 18 August 2006
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Metadata
Title
Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study
Authors
Kazuo Takiguchi
Akihito Uezato
Michio Itasaka
Hidenori Atsuta
Kenji Narushima
Naoki Yamamoto
Akeo Kurumaji
Makoto Tomita
Kazunari Oshima
Kosaku Shoda
Mai Tamaru
Masahito Nakataki
Mitsutoshi Okazaki
Sayuri Ishiwata
Yasuyoshi Ishiwata
Masato Yasuhara
Kunimasa Arima
Tetsuro Ohmori
Toru Nishikawa
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-017-1410-3

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