Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study
In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-respo...
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| Published in | Biological psychiatry (1969) Vol. 85; no. 7; pp. 596 - 605 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.04.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0006-3223 1873-2402 1873-2402 |
| DOI | 10.1016/j.biopsych.2018.09.009 |
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| Abstract | In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy.
Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups.
A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex.
Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ. |
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| AbstractList | AbstractBackgroundIn terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy. MethodsGlutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups. ResultsA total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels ( F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects ( p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex. ConclusionsTaken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ. In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy. Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups. A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex. Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ. In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy.BACKGROUNDIn terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy.Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups.METHODSGlutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups.A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex.RESULTSA total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex.Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ.CONCLUSIONSTaken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ. In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy. Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups. A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex. Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ. |
| Author | Nakajima, Shinichiro Iwata, Yusuke De Luca, Vincenzo Chavez, Sofia Mimura, Masaru Shah, Parita Remington, Gary Graff-Guerrero, Ariel Caravaggio, Fernando Mar, Wanna Plitman, Eric Kim, Julia Gerretsen, Philip |
| Author_xml | – sequence: 1 givenname: Yusuke surname: Iwata fullname: Iwata, Yusuke organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 2 givenname: Shinichiro surname: Nakajima fullname: Nakajima, Shinichiro organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 3 givenname: Eric surname: Plitman fullname: Plitman, Eric organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 4 givenname: Fernando surname: Caravaggio fullname: Caravaggio, Fernando organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 5 givenname: Julia surname: Kim fullname: Kim, Julia organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 6 givenname: Parita surname: Shah fullname: Shah, Parita organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 7 givenname: Wanna surname: Mar fullname: Mar, Wanna organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 8 givenname: Sofia surname: Chavez fullname: Chavez, Sofia organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 9 givenname: Vincenzo surname: De Luca fullname: De Luca, Vincenzo organization: Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 10 givenname: Masaru surname: Mimura fullname: Mimura, Masaru organization: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan – sequence: 11 givenname: Gary surname: Remington fullname: Remington, Gary organization: Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 12 givenname: Philip surname: Gerretsen fullname: Gerretsen, Philip organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada – sequence: 13 givenname: Ariel orcidid: 0000-0001-9301-2171 surname: Graff-Guerrero fullname: Graff-Guerrero, Ariel email: ariel_graff@yahoo.com.mx organization: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30389132$$D View this record in MEDLINE/PubMed |
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| Keywords | Treatment-resistant Schizophrenia 1H-MRS Antipsychotic Clozapine Glutamate H-MRS |
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| SubjectTerms | 1H-MRS Adult Antipsychotic Antipsychotic Agents - pharmacology Caudate Nucleus - diagnostic imaging Caudate Nucleus - metabolism Clozapine Cross-Sectional Studies Female Glutamate Glutamic Acid - metabolism Glutamine - metabolism Gyrus Cinguli - diagnostic imaging Gyrus Cinguli - metabolism Humans Male Middle Aged Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - metabolism Proton Magnetic Resonance Spectroscopy Psychiatric/Mental Health Schizophrenia Schizophrenia - diagnostic imaging Schizophrenia - drug therapy Schizophrenia - metabolism Treatment-resistant |
| Title | Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study |
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