TY - JOUR
T1 - Neuroanatomical profiles of treatment-resistance in patients with schizophrenia spectrum disorders
AU - Kim, Julia
AU - Plitman, Eric
AU - Iwata, Yusuke
AU - Nakajima, Shinichiro
AU - Mar, Wanna
AU - Patel, Raihaan
AU - Chavez, Sofia
AU - Chung, Jun Ku
AU - Caravaggio, Fernando
AU - Chakravarty, M. Mallar
AU - Remington, Gary
AU - Gerretsen, Philip
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
This work was supported by the CAMH Discovery Fund (J.K.), the Vanier Canada Graduate Scholarship (E.P.), the OMHF operating grant, and CIHR ( MOP-142493 and 14196 to A.G-G).
Funding Information:
J.K. has received funding from the CAMH Foundation and the Ontario Graduate Scholarship (OGS). E.P. has received funding from the Healthy Brains for Healthy Lives Postdoctoral Fellowship, the Vanier Canada Graduate Scholarship, the OGS, and the Canada Graduate Scholarship ? Master's. Y.I. has received fellowship grants from Keio University Medical Science Foundation, Mitsukoshi Foundation, Japan Foundation for Aging and Health, and manuscript fees from Dainippon Sumitomo Pharma. S.N. has received fellowship grants from the Canadian Institutes of Health Research (CIHR), research support from Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development, Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Uehara Memorial Foundation, and Daiichi Sankyo Scholarship Donation Program within the past 3 years. He has also received research support, manuscript fees, or speaker's honoraria from Dainippon Sumitomo Pharma, Meiji-Seika Pharma, Otsuka Pharmaceutical, Shionogi, and Yoshitomi Yakuhin within the past 3 years. J.K.C. has received funding from the CIHR Doctoral Award and the Canada Graduate Scholarship ? Master's. F.C. has received funding from CIHR, the Ontario Mental Health Post-Doctoral Fellowship Award, CAMH Foundation, the Brain & Behavior Research Foundation (Formerly NARSAD), and the Vancouver Coastal Health Research Institute. G.R. has received consultant fees from Neurocrine Biosciences and Synchroneuron, as well as research support from Novartis. P.G. reports receiving research support from CIHR, Ontario Ministry of Health and Long-Term Care, Ontario Mental Health Foundation (OMHF), and CAMH. A.G.-G. has received support from the United States National Institute of Health, CIHR, OMHF, Consejo Nacional de Ciencia y Tecnolog?a, the Instituto de Ciencia y Tecnolog?a del DF, the Brain & Behavior Research Foundation (Formerly NARSAD), the Ontario Ministry of Health and Long-Term Care, the Ontario Ministry of Research and Innovation Early Research Award, and Janssen. All other authors have declared that there are no conflicts of interest in relation to the subject of this study.This work was supported by the CAMH Discovery Fund (J.K.), the Vanier Canada Graduate Scholarship (E.P.), the OMHF operating grant, and CIHR (MOP-142493 and 14196 to A.G-G).
Publisher Copyright:
© 2019
PY - 2020/4/20
Y1 - 2020/4/20
N2 - Widespread structrual abnormalities in subcortical brain regions have been identified in patients with schizophrenia. However, only a few studies have examined the neuroanatomical profiles of patients with treatment-resistant schizophrenia. The aim of this study was to compare differences in subcortical and hippocampal volumes between: (i) treatment-resistant patients who are non-responders to both first-line antipsychotics and clozapine (URS), (ii) treatment-resistant patients who are non-responders to first-line antipsychotics but are responders to clozapine (CLZ-Resp), (iii) responders to first-line antipsychotics (FL-Resp), and (iv) healthy controls. T1-weighted images of 103 participants (27 URS, 29 CLZ-Resp, 21 FL-Resp, and 26 healthy controls) were obtained. Group differences in striatal, thalamic, globus pallidus, amygdala, and hippocampus volumes were examined. Multiple regression analyses were performed to examine the associations between subcortical and hippocampal volumes and participant characteristics. The FL-Resp group showed larger striatal and globus pallidus volumes compared to the URS group and larger post-commissural putamen and globus pallidus volumes compared to healthy controls. The URS group showed smaller thalamic volume compared to healthy controls. There were no subcortical or hippocampal volume differences between the URS and CLZ-Resp groups. Differences in subcortical and hippocampal structural volumes were not related to symptom severity or chlorpromazine antipsychotic dose equivalents. Our findings suggest different structural volume alterations in subcortical brain regions between treatment-resistant schizophrenia and responders to first-line antipsychotics. Whether subcortical structure compromise is a distinct pathophysiological marker of treatment-resistant schizophrenia, or a result of antipsychotic exposure, remains to be explored.
AB - Widespread structrual abnormalities in subcortical brain regions have been identified in patients with schizophrenia. However, only a few studies have examined the neuroanatomical profiles of patients with treatment-resistant schizophrenia. The aim of this study was to compare differences in subcortical and hippocampal volumes between: (i) treatment-resistant patients who are non-responders to both first-line antipsychotics and clozapine (URS), (ii) treatment-resistant patients who are non-responders to first-line antipsychotics but are responders to clozapine (CLZ-Resp), (iii) responders to first-line antipsychotics (FL-Resp), and (iv) healthy controls. T1-weighted images of 103 participants (27 URS, 29 CLZ-Resp, 21 FL-Resp, and 26 healthy controls) were obtained. Group differences in striatal, thalamic, globus pallidus, amygdala, and hippocampus volumes were examined. Multiple regression analyses were performed to examine the associations between subcortical and hippocampal volumes and participant characteristics. The FL-Resp group showed larger striatal and globus pallidus volumes compared to the URS group and larger post-commissural putamen and globus pallidus volumes compared to healthy controls. The URS group showed smaller thalamic volume compared to healthy controls. There were no subcortical or hippocampal volume differences between the URS and CLZ-Resp groups. Differences in subcortical and hippocampal structural volumes were not related to symptom severity or chlorpromazine antipsychotic dose equivalents. Our findings suggest different structural volume alterations in subcortical brain regions between treatment-resistant schizophrenia and responders to first-line antipsychotics. Whether subcortical structure compromise is a distinct pathophysiological marker of treatment-resistant schizophrenia, or a result of antipsychotic exposure, remains to be explored.
KW - Antipsychotics
KW - Clozapine
KW - Hippocampus
KW - Subcortical
KW - Treatment-resistant schizophrenia
KW - Volume
UR - http://www.scopus.com/inward/record.url?scp=85076518277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076518277&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2019.109839
DO - 10.1016/j.pnpbp.2019.109839
M3 - Article
C2 - 31843627
AN - SCOPUS:85076518277
SN - 0278-5846
VL - 99
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 109839
ER -