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Randomized Controlled Trial
. 2017 Jul 12;17(1):249.
doi: 10.1186/s12888-017-1410-3.

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

Kazuo Takiguchi  1   2 , Akihito Uezato  1 , Michio Itasaka  1 , Hidenori Atsuta  1 , Kenji Narushima  1 , Naoki Yamamoto  1   3 , Akeo Kurumaji  1 , Makoto Tomita  4 , Kazunari Oshima  1   5 , Kosaku Shoda  5 , Mai Tamaru  6 , Masahito Nakataki  6 , Mitsutoshi Okazaki  7 , Sayuri Ishiwata  1 , Yasuyoshi Ishiwata  8 , Masato Yasuhara  8 , Kunimasa Arima  7 , Tetsuro Ohmori  6 , Toru Nishikawa  9
Affiliations
Randomized Controlled Trial

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

Kazuo Takiguchi et al. BMC Psychiatry. .

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.

Keywords: Crossover; D-cycloserine; Double-blind; Glutamate; MR diffusion tensor imaging; Placebo-controlled; Randomized; Schizophrenia.

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Conflict of interest statement

Ethics approval and consent to participate

This study was performed after approval by the Ethics Committee of each institution (Institutional Review Board of Tokyo Medical and Dental University Medical Hospital (No. 17–14), Research Ethics Committee of National Center of Neurology and Psychiatry (A2010–013), Ethics Committee of Tokushima University Hospital (No. 1154–1), Institutional Review Board of Haryugaoka Hospital (No. 2), Ethics Committee of Ohmiya Kousei Hospital (No. 5)). Prior to study initiation, the study was sufficiently explained orally and using documents to all subjects and/or their families and voluntary written consent was obtained.

Consent for publication

Consent for publication was included in the consent for study participation.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT flow of participants through the trial
Fig. 2
Fig. 2
Changes in the scores of PANSS negative symptom PANSS, Positive and Negative Syndrome Scale; DCS-effect was defined by scores at DCS phase subtracted by those at PCB phase. In the non-EOS group, the scores for both DCS and PCB declined as time proceeded and almost no difference (−0.07) was noted in the DCS-effect at 6 W. In the EOS group, the score for PCB declined as time proceeded whereas the one for DCS demonstrated less decline or even an increase, resulting in the positive value (+2.2) for the DCS-effect at 6 W
See this image and copyright information in PMC

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