An amendment to this paper has been published and can be accessed via a link at the top of the paper

Hashimoto, RI

Ichikawa, N

Kasai, K

Kato, N

Kawato, M

Lisi, G

Mimura, M

Moriguchi, S

Morimoto, J

Okada, G

Okamoto, Y

Seymour, B

Suhara, T

Takahashi, H

Takamura, M

Yahata, N

Yamada, M

Yamada, T

Yamawaki, S

Yoshihara, Y

Abstract: The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future

Ichikawa, Naho

Lisi, Giuseppe

Yahata, Noriaki

Okada, Go

Takamura, Masahiro

Hashimoto, Ryu-ichiro

Yamada, Takashi

Yamada, Makiko

Suhara, Tetsuya

Moriguchi, Sho

Mimura, Masaru

Yoshihara, Yujiro

Takahashi, Hidehiko

Kasai, Kiyoto

Kato, Nobumasa

Yamawaki, Shigeto

Seymour, Ben

Kawato, Mitsuo

Morimoto, Jun

Okamoto, Yasumasa

Apollo (Cambridge)

English

Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants

1Vol.:(0123456789)Scientific Reports |        (2020) 10:17650  | https://doi.org/10.1038/s41598-020-73436-ywww.nature.com/scientificreportsPublisher Correction: Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressantsNaho Ichikawa, Giuseppe Lisi, Noriaki Yahata, Go Okada, Masahiro Takamura, Ryu‑ichiro Hashimoto, Takashi Yamada, Makiko Yamada, Tetsuya Suhara, Sho Moriguchi, Masaru Mimura, Yujiro Yoshihara, Hidehiko Takahashi, Kiyoto Kasai, Nobumasa Kato, Shigeto Yamawaki, Ben Seymour, Mitsuo Kawato, Jun Morimoto & Yasumasa OkamotoCorrection to: Scientific Reports https ://doi.org/10.1038/s4159 8-020-60527 -z , published online 26 February 2020.The original version of this Article contained errors.In the original PDF version, the published date was omitted and now reads:“Published: 26 February 2020”.In addition, there were typographical errors in the Methods section, under the subheading “Experimental pro-tocol and data acquisition”, where:“In the scan room with dimmed lights, participants were not required to keep looking at a cross mark in the center of the monitor screen, think of anything in particular, and not to sleep.”now reads:“In the scan room with dimmed lights, participants were required to keep looking at a cross mark in the center of the monitor screen, think of nothing in particular, and not to sleep.”In Table 2 where the ‘Contribution’ value for ID #7 was incorrect, the value “\” now reads “0.263”.In the Results section under the subheading “Effect of treatment with antidepressants”, where BDI and HAMD values were reversed,“(Mean(SD): BDI Pre = 19.1 (5.63), BDI Post = 11.3 (5.41), paired t-test results on BDI: p = 7.29 × 10−7; and HAMD Pre = 31.3 (7.48), HAMD Post = 18.7 (12.2), paired t-test results on HAMD: p = 7.26 × 10−7).”now reads:“(Mean(SD): BDI Pre = 31.3 (7.48), BDI Post = 18.7 (12.2), paired t-test results on BDI: p = 7.26 ×  10−7; and HAMD Pre = 19.1 (5.63), HAMD Post = 11.3 (5.41), paired t-test results on HAMD: p = 7.29 ×  10−7).”In the Supplementary Information file, there were missing values in Table S1c under the “Time 2 (6-8w)” column and on the “Severity of symptoms (BDI-II) “and “Observer-rated depression scale (HAMD-17)” rows. These values now read “18.7 (12.2)” and “11.3 (5.4)” respectively.OPEN2Vol:.(1234567890)Scientific Reports |        (2020) 10:17650  | https://doi.org/10.1038/s41598-020-73436-ywww.nature.com/scientificreports/These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/.© The Author(s) 2020

Publisher Correction: Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants

1Vol.:(0123456789)Scientific Reports |        (2020) 10:17650  | https://doi.org/10.1038/s41598-020-73436-ywww.nature.com/scientificreportsPublisher Correction: Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressantsNaho Ichikawa, Giuseppe Lisi, Noriaki Yahata, Go Okada, Masahiro Takamura, Ryu‑ichiro Hashimoto, Takashi Yamada, Makiko Yamada, Tetsuya Suhara, Sho Moriguchi, Masaru Mimura, Yujiro Yoshihara, Hidehiko Takahashi, Kiyoto Kasai, Nobumasa Kato, Shigeto Yamawaki, Ben Seymour, Mitsuo Kawato, Jun Morimoto & Yasumasa OkamotoCorrection to: Scientific Reports https ://doi.org/10.1038/s4159 8-020-60527 -z , published online 26 February 2020.The original version of this Article contained errors.In the original PDF version, the published date was omitted and now reads:“Published: 26 February 2020”.In addition, there were typographical errors in the Methods section, under the subheading “Experimental pro-tocol and data acquisition”, where:“In the scan room with dimmed lights, participants were not required to keep looking at a cross mark in the center of the monitor screen, think of anything in particular, and not to sleep.”now reads:“In the scan room with dimmed lights, participants were required to keep looking at a cross mark in the center of the monitor screen, think of nothing in particular, and not to sleep.”In Table 2 where the ‘Contribution’ value for ID #7 was incorrect, the value “\” now reads “0.263”.In the Results section under the subheading “Effect of treatment with antidepressants”, where BDI and HAMD values were reversed,“(Mean(SD): BDI Pre = 19.1 (5.63), BDI Post = 11.3 (5.41), paired t-test results on BDI: p = 7.29 × 10−7; and HAMD Pre = 31.3 (7.48), HAMD Post = 18.7 (12.2), paired t-test results on HAMD: p = 7.26 × 10−7).”now reads:“(Mean(SD): BDI Pre = 31.3 (7.48), BDI Post = 18.7 (12.2), paired t-test results on BDI: p = 7.26 × 10−7; and HAMD Pre = 19.1 (5.63), HAMD Post = 11.3 (5.41), paired t-test results on HAMD: p = 7.29 × 10−7).”In the Supplementary Information file, there were missing values in Table S1c under the “Time 2 (6-8w)” column and on the “Severity of symptoms (BDI-II) “and “Observer-rated depression scale (HAMD-17)” rows. These values now read “18.7 (12.2)” and “11.3 (5.4)” respectively.OPEN2Vol:.(1234567890)Scientific Reports |        (2020) 10:17650  | https://doi.org/10.1038/s41598-020-73436-ywww.nature.com/scientificreports/These errors have now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/.© The Author(s) 2020

The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second 'most important' FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future

Hashimoto, Ryu-Ichiro

Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants.

The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future

CUED - Cambridge University Engineering Department

https://www.repository.cam.ac.uk/bitstream/1810/311486/2/41598_2020_Article_73436.pdf

Publisher Correction: Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants

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