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1. Minimally Invasive Direct Internal Cyclopexy in the Management of Goniotomy-Related Cyclodialysis Cleft with Hypotony Maculopathy

Author

Matsuo M, Ichioka S, Harano A, Takayanagi Y, and Tanito M

Subjects
cyclopexy, cyclodialysis cleft, hypotony maculopathy, ab-interno trabeculotomy, surgical complication., Medicine (General), R5-920
Abstract

Masato Matsuo,1,2 Sho Ichioka,1 Akiko Harano,1 Yuji Takayanagi,1 Masaki Tanito1 1Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Japan; 2Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, JapanCorrespondence: Masato Matsuo, Department of Ophthalmology, Shimane University Faculty of Medicine, Enya 89-1, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2284, Fax +81-853-20-2278, Email matsuondmc@gmail.comIntroduction: Although ab-interno trabeculotomy-related (goniotomy-related) surgeries has a favorable safety profile, cyclodialysis cleft refractory to conservative management could occur, thereby requiring additional surgical treatment. External and, more recently, internal cycloplexy have been attempted to treat cyclodialysis clefts with hypotony maculopathy, however the traditional methods require conjunctival or scleral incisions and have been inappropriate for glaucoma patients who need to undergo future trabeculectomy. Therefore, we report two cases who underwent a novel reliable technique for suture fixation of the detached ciliary body onto the original scleral bed directly through the intraocular approach without conjunctival or scleral incision, minimally invasive direct internal cyclopexy, in the management of goniotomy-related cyclodialysis cleft with hypotony maculopathy.Case Description: Goniotomy-related cyclodialysis cleft exceeded 45° and vision-threatening hypotony maculopathy was observed in two eyes in two patients with normal tension glaucoma and myopia gravis without a prior history of trauma who had undergone Kahook Dual Blade goniotomy combined with cataract surgery. The patients were followed conservatively for a while, however the cyclodialysis clefts and hypotony maculopathies did not resolve. Therefore, a 72-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 65 after the goniotomy, and another 67-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 149. In both cases, topical antibiotic and steroid eye drops were prescribed postoperatively. The cyclodialysis clefts were repaired successfully; however, the latter patient developed delayed-onset acute transient ocular hypertension 33 days after minimally invasive direct internal cyclopexy and required glaucoma medications. The hypotony maculopathies resolved approximately 3 months after suturing, and eventually visual acuity improved from preoperative levels and good intraocular pressure control was achieved in both. No further postoperative complications have been observed to date.Conclusion: We successfully managed two cases of goniotomy-related cyclodialysis cleft with hypotony maculopathy using minimally invasive direct internal cyclopexy.Keywords: cyclopexy, cyclodialysis cleft, hypotony maculopathy, ab-interno trabeculotomy, surgical complication

Published
2024

2. Vector analysis investigation of toric intraocular lens with no deviation from the intended axis

Author

Kawahara A and Takayanagi Y

Subjects
cataract surgery, astigmatism, toric intraocular lens, Ophthalmology, RE1-994
Abstract

Atsushi Kawahara,1,2 Yoshinori Takayanagi1 1Takayanagi Clinic, Kushiro, 2Sapporo Kato Eye Clinic, Sapporo, Hokkaido, Japan Aim: The aim of this research was to evaluate vector analysis after implantation of toric intraocular lenses (IOLs) without deviation from the intended axis. Methods: The study included 18 eyes of 16 patients who underwent cataract surgery with the insertion of a toric implant (AcrySof IQ Toric). The postoperative IOL meridian placement completely corresponded to that planned. Using vector analysis, surgically induced astigmatism (SIA) was derived from the refractive outcome versus the predicted postoperative keratometric astigmatism and was compared with targeted induced astigmatism (TIA). The difference vector (DV) was derived by calculating the vector expression of the remaining astigmatic change. Results: The mean postoperative remaining refractive astigmatism of 0.73±0.55 diopters (D) was achieved versus the mean target of 0.44±0.28 D. There was a difference of 0.29 D between the target and achieved values. The mean SIA value was 1.90±0.99 D compared with the mean TIA value of 2.00±0.85 D. The mean DV value was 0.87±0.56 D. The astigmatism correction index (SIA/TIA) was 0.95, which was near the ideal value of 1. The index of success (DV/TIA) was 0.44, which was far from the ideal value of 0. Conclusion: The implantation of toric IOLs is an effective, predictable method for astigmatic correction. However, some remaining astigmatism is present even if toric IOLs are placed accurately. Keywords: cataract surgery, astigmatism, toric intraocular lens, alpins method, toric calculator, remaining astigmatism

Published
2016

3. Comparison of effect of nepafenac and diclofenac ophthalmic solutions on cornea, tear film, and ocular surface after cataract surgery: the results of a randomized trial

Author

Kawahara A, Utsunomiya T, Kato Y, and Takayanagi Y

Subjects
nepafenac, diclofenac, cornea, tear film, ocular surface, cataract surgery, Ophthalmology, RE1-994
Abstract

Atsushi Kawahara,1–3 Tsugiaki Utsunomiya,4 Yuji Kato,2 Yoshinori Takayanagi3 1Department of Ophthalmology, Sapporo Tokushukai Hospital, Sapporo, Hokkaido, Japan; 2Sapporo Kato Eye Clinic, Sapporo, Hokkaido, Japan; 3Takayanagi Clinic, Kushiro, Hokkaido, Japan; 4Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan Background: The aim of this study was to compare the effects of nepafenac ophthalmic suspension 0.1% (Nevanac) and diclofenac sodium ophthalmic solution 0.1% (Diclod) on the cornea, tear film, and ocular surface after cataract surgery. Methods: A total of 60 eyes (60 patients) were selected for this study, with no ocular diseases other than cataract (scheduled for cataract surgery by one surgeon). Patients were randomly enrolled to receive nepafenac or diclofenac in the perioperative period, and cataract surgery was performed using torsional microcoaxial phacoemulsification and aspiration with intraocular lens implantation via a transconjunctival single-plane sclerocorneal incision at the 12 o’clock position. We compared intra- and intergroup differences preoperatively and postoperatively in conjunctival and corneal fluorescein staining scores, tear film breakup times, Schirmer’s tests, the Dry Eye Related Quality of Life Scores, and tear meniscus areas using anterior segment optical coherence tomography. Results: The diclofenac group had significantly higher conjunctival and corneal fluorescein staining scores at 4 weeks postoperatively compared with the nepafenac group (P

Published
2016

4. Superconducting pairing and the pseudogap in nematic striped La2-xSrxCuO4

Author

Sugai, S., Takayanagi, Y., Hayamizu, N., Muroi, T., Shiozaki, R., Nohara, J., Takenaka, K., and Okazaki, K.

Subjects
Condensed Matter - Superconductivity
Abstract

The individual k\parallel and k\perp stripe excitations in fluctuating spin-charge stripes have not been observed yet. In Raman scattering if we set, for example, incident and scattered light polarizations to two possible stripe directions, we can observe the fluctuating stripe as if it is static. Using the different symmetry selection rule between the B1g two-magnon scattering and the B1g and B2g isotropic electronic scattering, we succeeded to obtain the k\parallel and k\perp strip magnetic excitations separately in La2-xSrxCuO4. Only the k\perp stripe excitations appear in the wide-energy isotropic electronic Raman scattering, indicating that the charge transfer is restricted to the direction perpendicular to the stripe. This is the same as the Burgers vector of an edge dislocation which easily slides perpendicularly to the stripe. Hence charges at the edge dislocation move together with the dislocation perpendicularly to the stripe, while other charges are localized. A looped edge dislocation has lower energy than a single edge dislocation. The superconducting coherence length is close to the inter-charge stripe distance at x \le 0.2. Therefore we conclude that Cooper pairs are formed at looped edge dislocations. The restricted charge transfer direction naturally explains the opening of a pseudogap around (0, {\pi}) for the stripe parallel to the b axis and the reconstruction of the Fermi surface to have a flat plane near (0, {\pi}). They break the four-fold rotational symmetry. Furthermore the systematic experiments revealed the carrier density dependence of the isotropic and anisotropic electronic excitations, the spin density wave and/or charge density wave gap near ({\pi}/2, {\pi}/2), and the strong coupling between the electronic states near ({\pi}/2, {\pi}/2) and the zone boundary phonons at ({\pi}, {\pi})., Comment: 26 pages, 24 figures

Published
2013
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5. Raman Studies of Anisotropic Magnetic Excitations in Fluctuating Nematic Striped La2-xSrxCuO4 and the Comparison to Uniform Nd2-xCexCuO4

Author

Sugai, S., Takayanagi, Y., Hayamizu, N., Sone, Y., Nakagawa, N., and Muroi, T.

Subjects
Condensed Matter - Superconductivity
Abstract

The mechanism of the high temperature hole-doped superconductivity was investigated by Raman scattering. The Raman selection rule is unique, so that anisotropic magnetic excitations in a fluctuating spin-charge stripe can be detected as if it is static. We use different Raman selection rules for two kinds of magnetic Raman scattering processes, two-magnon scattering and high-energy electronic scattering. In order to confirm the difference, the Raman spectra of striped La2-xSrxCuO4 (LSCO) and non-striped Nd2-xCexCuO4 (NCCO) were compared. The main results in LSCO are (1) magnetic excitations are presented by individual energy dispersions for the k\parallel stripe and the k\perp stripe, (2) the charge transfer is allowed only in the direction perpendicular to the stripe. The direction is the same as the Burgers vector of an edge dislocation. Hence we assume that a charge moves together with the edge dislocation of the charge stripe. The superconducting coherence length is close to the inter-charge stripe distance at x < 0.2. Therefore we propose a model that superconducting pairs are formed in the edge dislocations. The binding energy is related to the stripe formation energy., Comment: 5 pages, 3 figures, International Conference on Superstripes 2012: Phase Separation and Superstripes in High Temperature Superconductors and Related Materials, 11-17 July, 2012, Erice-Sicily, Italy

Published
2013

6. Magnetic and Electronic Raman Scattering at the Nodal Spin-Density-Wave Transition in BaFe2As2

Author

Sugai, S., Mizuno, Y., Watanabe, R., Kawaguchi, T., Takenaka, K., Ikuta, H., Takayanagi, Y., Hayamizu, N., and Sone, Y.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Strongly Correlated Electrons
Abstract

Two magnon excitations and the nodal spin density wave (SDW) gap were observed in BaFe2As2 by Raman scattering. Below the SDW transition temperature (TSDW) nodal SDW gap opens together with new excitations in reconstructed electronic states. The two-magnon peak remains above TSDW and moreover the energy increases a little. The change from the long-range ordered state to the short-range correlated state is compared to the cuprate superconductors., Comment: 5 pages, 3 figures

Published
2010

7. Difference between the cleaved surface and the polished surface on the Raman spectra of La$_{2-x}$Sr$_x$CuO$_4$

Author

Sugai, S., Takayanagi, Y., and Hayamizu, N.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Strongly Correlated Electrons
Abstract

The Raman spectra on the cleaved surface of La$_{2-x}$Sr$_x$CuO$_4$ is found to be different from those on the mechanically polished or chemically etched surface. On the cleaved surface, the step-like increase of the scattering intensity below 700 cm$^{-1}$ is washed away and the two-phonon peaks are preserved clearly even at the optimum doping. The difference is demonstrated on the optimally doped crystal at x=0.15 and the stripe phase crystal at x=0.115. The stripe phase is stabilized by defects induced by mechanical polishing., Comment: 9 pages, 4 figures

Published
2000

8. O-015 Results of urological consultation in the setting of IVF clinic

Author

Komiya, A, primary, Kawai, K, additional, Sujino, T, additional, Iijima, M, additional, Tsukamoto, S, additional, Kato, M, additional, Tajima, M, additional, Takayanagi, Y, additional, Nako, Y, additional, Hiraoka, K, additional, Uchida, N, additional, Ishikawa, S, additional, and Ichikawa, T, additional

Published
2022
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9. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, Paus, T, Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, and Paus, T

Abstract

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t

Published
2022

10. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., Paus, T., Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A., Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.-M., Landén, M., Landrø, N.I., Lawrie, S., Lebedeva, I., Luna, B., Lundervold, A.J., MacMaster, F.P., Maglanoc, L.A., Mathalon, D.H., McDonald, C., McIntosh, A., Meinert, S., Michie, P.T., Mitchell, P., Moreno-Alcázar, A., Mowry, B., Muratori, F., Nabulsi, L., Nenadić, I., O'Gorman Tuura, R., Oosterlaan, J., Overs, B., Pantelis, C., Parellada, M., Pariente, J.C., Pauli, P., Pergola, G., Piarulli, F.M., Picon, F., Piras, F., Pomarol-Clotet, E., Pretus, C., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Reif, A., Retico, A., Roberts, G., Rossell, S., Rovaris, D.L., Rubia, K., Sacchet, M., Salavert, J., Salvador, R., Sarró, S., Sawa, A., Schall, U., Scott, R., Selvaggi, P., Silk, T., Sim, K., Skoch, A., Spalletta, G., Spaniel, F., Stein, D.J., Steinsträter, O., Stolicyn, A., Takayanagi, Y., Tamm, L., Tavares, M., Teumer, A., Thiel, K., Thomopoulos, S.I., Tomecek, D., Tomyshev, A.S., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Rheenen, T., Vazquez-Bourgón, J., Vernooij, M.W., Vieta, E., Vilarroya, O., Weickert, C., Weickert, T., Westlye, L.T., Whalley, H., Willinger, D., Winter, A., Wittfeld, K., Yang, T.T., Yoncheva, Y., Zijlmans, J.L., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J., Ching, C.R.K., Andreassen, O.A., Pozzi, E., Veltman, D., Schmaal, L., van Erp, T.G.M., Turner, J., Castellanos, F.X., Pausova, Z., Thompson, P., and Paus, T.

Abstract

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t

Published
2022
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14. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, Paus, T, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, and Paus, T

Abstract

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene

Published
2021

15. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., Paus, T., Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., and Paus, T.

Abstract

Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (exce

Published
2021
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20. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA

Author

Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quidé, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadić, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodríguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Stäblein, M, Oertel, V, Knöchel, C, Borgwardt, S, du Plessis, S, Yun, JY, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Díaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, López-Jaramillo, C, Díaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, van Erp, T, Glahn, D, Pearlson, G, Hong, E, Krug, A, Carr, V, Tooney, P, Cooper, G, Rasser, P, Michie, P, Catts, S, Gur, R, Yang, F, Fan, F, Chen, J, Guo, H, Tan, S, Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quidé, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadić, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodríguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Stäblein, M, Oertel, V, Knöchel, C, Borgwardt, S, du Plessis, S, Yun, JY, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Díaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, López-Jaramillo, C, Díaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, van Erp, T, Glahn, D, Pearlson, G, Hong, E, Krug, A, Carr, V, Tooney, P, Cooper, G, Rasser, P, Michie, P, Catts, S, Gur, R, Yang, F, Fan, F, Chen, J, Guo, H, and Tan, S

Abstract

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Published
2020

21. Increased power by harmonizing structural MRI site differences with the ComBat batch method in ENIGMA

Author

Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quide, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadic, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodriguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Staeblein, M, Oertel, V, Knoechel, C, Borgwardt, S, du Plessis, S, Yun, J-Y, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Diaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, Lopez-Jaramillo, C, Diaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, van Erp, T, Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quide, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadic, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodriguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Staeblein, M, Oertel, V, Knoechel, C, Borgwardt, S, du Plessis, S, Yun, J-Y, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Diaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, Lopez-Jaramillo, C, Diaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, and van Erp, T

Abstract

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Published
2020

26. Oxytocin and appetite

Author

LENG, G, primary, ONAKA, T, additional, CAQUINEAU, C, additional, SABATIER, N, additional, TOBIN, V, additional, and TAKAYANAGI, Y, additional

Published
2008
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33. Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium

Author

Horiuchi, Y, primary, Kondo, M A, additional, Okada, K, additional, Takayanagi, Y, additional, Tanaka, T, additional, Ho, T, additional, Varvaris, M, additional, Tajinda, K, additional, Hiyama, H, additional, Ni, K, additional, Colantuoni, C, additional, Schretlen, D, additional, Cascella, N G, additional, Pevsner, J, additional, Ishizuka, K, additional, and Sawa, A, additional

Published
2016
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35. P.1.i.042 Cortical thickness changes in individuals at risk of psychosis

Author

Sasabayashi, D., primary, Takayanagi, Y., additional, Nakamura, M., additional, Takahashi, T., additional, Furuichi, A., additional, Kido, M., additional, Nishikawa, Y., additional, Katagiri, N., additional, Sakuma, A., additional, Koike, S., additional, Yamasue, H., additional, Matsumoto, K., additional, Mizuno, M., additional, Kasai, K., additional, and Suzuki, M., additional

Published
2015
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37. Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine

Author

K. Sasaki, Ryousuke Fujita, Takayanagi Y, Takayanagi M, and Masaaki Ishikawa

Subjects
Azides, Dihydropyridines, Pharmacology, Rhodamine 123, Binding, Competitive, chemistry.chemical_compound, Antimalarials, medicine, Tumor Cells, Cultured, Humans, Doxorubicin, ATP Binding Cassette Transporter, Subfamily B, Member 1, Cytotoxicity, Coloring Agents, P-glycoprotein, Antibiotics, Antineoplastic, biology, Mefloquine, Affinity Labels, Drug Synergism, Calcium Channel Blockers, Drug Resistance, Multiple, Multiple drug resistance, Phenotype, chemistry, Verapamil, Drug Resistance, Neoplasm, biology.protein, Efflux, medicine.drug
Abstract

We studied the effect of the antimalarial drug mefloquine on the resistance of K562 cells to doxorubicin. Mefloquine synergistically potentiated the cytotoxicity of doxorubicin for doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 0.5-3 microM, but had hardly any synergistic effect in the parental cell line (K562) at the same concentration. Mefloquine was more potent than verapamil, a known modulator of multidrug-resistance. Since doxorubicin resistance in these cells is associated with the expression of high levels of P-glycoprotein, we evaluated the effect of mefloquine and of P-glycoprotein activity in cytofluorographic efflux experiments with the fluorescent dye rhodamine 123. Our results indicate that mefloquine inhibits the P-glycoprotein pump-efflux activity in a dose-related manner. Moreover, mefloquine reduces the expression of the immunoreactive P-glycoprotein in K562/DXR cells as evaluated by cytofluorimetric assay. Taken together, the results indicate that mefloquine reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.

Published
2000

38. Stripe-Induced High-Temperature Superconductivity in Cuprates

Author

Sugai, S., primary, Takayanagi, Y., additional, Nohara, J., additional, Shiozaki, R., additional, Hayamizu, N., additional, Muroi, T., additional, Hosokawa, T., additional, Suzuki, H., additional, Sone, Y., additional, Mabuchi, H., additional, Takenaka, K., additional, and Okazaki, K., additional

Published
2013
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42. Genome-wide profiling of multiple histone methylations in olfactory cells: further implications for cellular susceptibility to oxidative stress in schizophrenia

Author

Kano, S, primary, Colantuoni, C, additional, Han, F, additional, Zhou, Z, additional, Yuan, Q, additional, Wilson, A, additional, Takayanagi, Y, additional, Lee, Y, additional, Rapoport, J, additional, Eaton, W, additional, Cascella, N, additional, Ji, H, additional, Goldman, D, additional, and Sawa, A, additional

Published
2012
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44. Inhibition of cell proliferation by Rana catesbeiana and Rana japonica lectins belonging to the ribonuclease superfamily

Author

Nitta K, Kouichi Ozaki, Ishikawa M, Furusawa S, Hosono M, Kawauchi H, Sasaki K, Takayanagi Y, Tsuiki S, and Hakomori S

Subjects
Agglutination, Rana catesbeiana, Ranidae, Cell Survival, Antineoplastic Agents, Neoplasms, Experimental, Chromatography, Affinity, Cell Line, Rats, Mice, Ribonucleases, Lectins, Polyamines, Animals, Glycoconjugates, Cell Division, Glycosaminoglycans
Abstract

Two frog egg lectins [Rana catesbeiana lectin (SBL-C) and Rana japonica lectin] preferentially agglutinate a large variety of human and animal tumor cells but not blood cells, lymphocytes, or fibroblasts. These lectins belong to the superfamily of pyrimidine base-specific RNases. The two lectins bound to a heparin-Sepharose column and were eluted from the column by an increase of NaCl molarity. Both their tumor cell-agglutinating activity and RNase activity were inhibited by heparin, and also by polyamines, such as spermine. Both lectins inhibited P388 leukemia cell proliferation. The inhibitory activity of SBL-C was blocked by addition of heparin. SBL-C inhibited protein synthesis by P388 cells, but RNase A did not. No lectin-induced antiproliferative effect was observed after sialidase treatment of cells. The antiproliferative activity of SBL-C was also inhibited by ammonium chloride treatment. These results suggest that internalization of the lectins by lectin receptor (sialoglycoconjugate)-mediated endocytosis is followed by cell death due to inhibition of protein synthesis. Administration of SBL-C i.p. delayed time to death in mice receiving i.p. transplants of Sarcoma 180 and Mep II cells.

Published
1994

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