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Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies

Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (...

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Published in:Psychological medicine 2024-11, Vol.54 (15), p.1-4082
Main Authors: Zhang, Jiayuan, Toulopoulou, Timothea, Li, Qian, Niu, Lijing, Peng, Lanxin, Dai, Haowei, Chen, Keyin, Wang, Xingqin, Huang, Ruiwang, Wei, Xinhua, Zhang, Ruibin
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container_issue 15
container_start_page 1
container_title Psychological medicine
container_volume 54
creator Zhang, Jiayuan
Toulopoulou, Timothea
Li, Qian
Niu, Lijing
Peng, Lanxin
Dai, Haowei
Chen, Keyin
Wang, Xingqin
Huang, Ruiwang
Wei, Xinhua
Zhang, Ruibin
description Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.BACKGROUNDPsychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.METHODSWe examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.RESULTSStatistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112
doi_str_mv 10.1017/S0033291724001673
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Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.BACKGROUNDPsychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.METHODSWe examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.RESULTSStatistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.Altered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.CONCLUSIONSAltered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.</description><identifier>ISSN: 1469-8978</identifier><identifier>ISSN: 0033-2917</identifier><identifier>EISSN: 1469-8978</identifier><identifier>DOI: 10.1017/S0033291724001673</identifier><identifier>PMID: 39564744</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Original</subject><ispartof>Psychological medicine, 2024-11, Vol.54 (15), p.1-4082</ispartof><rights>The Author(s) 2024 2024 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924,33611,34530</link.rule.ids></links><search><creatorcontrib>Zhang, Jiayuan</creatorcontrib><creatorcontrib>Toulopoulou, Timothea</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Niu, Lijing</creatorcontrib><creatorcontrib>Peng, Lanxin</creatorcontrib><creatorcontrib>Dai, Haowei</creatorcontrib><creatorcontrib>Chen, Keyin</creatorcontrib><creatorcontrib>Wang, Xingqin</creatorcontrib><creatorcontrib>Huang, Ruiwang</creatorcontrib><creatorcontrib>Wei, Xinhua</creatorcontrib><creatorcontrib>Zhang, Ruibin</creatorcontrib><title>Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies</title><title>Psychological medicine</title><description>Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.BACKGROUNDPsychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.METHODSWe examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.RESULTSStatistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.Altered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.CONCLUSIONSAltered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.</description><subject>Original</subject><issn>1469-8978</issn><issn>0033-2917</issn><issn>1469-8978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpVjV1LwzAYhYMobk5_gHe59Kaat0ma5krm0E2YCE6vy9s23SL9WpIO-u8duAu9OgfOw3MIuQV2DwzUw4YxzmMNKhaMQaL4GZmCSHSUapWe_-kTcuX995HhIOJLMuFaJkIJMSVhsUMXbLuluUPb0uX8aU6xLem2HgI2GAytzcHUnmLhOu9p78diZzE4W9DS-s6Vxnmaj3Q_YBtswGAP5mjAevTW066iEAOFVfT2saE-DKU1_ppcVFh7c3PKGfl6ef5crKL1-_J1MV9HfQwqRFpqU-o0ZaYCLCsBgFJrnijkOi6r2BghQUiW6FRqBQnneYVpwmUucswrwWfk8dfbD3ljysK0wWGd9c426MasQ5v9X1q7y7bdIQNIJIPj14zcnQyu2w_Gh6yxvjB1ja3pBp9x4CyNtRTAfwAcG3h4</recordid><startdate>20241120</startdate><enddate>20241120</enddate><creator>Zhang, Jiayuan</creator><creator>Toulopoulou, Timothea</creator><creator>Li, Qian</creator><creator>Niu, Lijing</creator><creator>Peng, Lanxin</creator><creator>Dai, Haowei</creator><creator>Chen, Keyin</creator><creator>Wang, Xingqin</creator><creator>Huang, Ruiwang</creator><creator>Wei, Xinhua</creator><creator>Zhang, Ruibin</creator><general>Cambridge University Press</general><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20241120</creationdate><title>Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies</title><author>Zhang, Jiayuan ; Toulopoulou, Timothea ; Li, Qian ; Niu, Lijing ; Peng, Lanxin ; Dai, Haowei ; Chen, Keyin ; Wang, Xingqin ; Huang, Ruiwang ; Wei, Xinhua ; Zhang, Ruibin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p217t-959ed9880ef1adf411a599367a392df2ee4514506985971633bfa8635b4babf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Original</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jiayuan</creatorcontrib><creatorcontrib>Toulopoulou, Timothea</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Niu, Lijing</creatorcontrib><creatorcontrib>Peng, Lanxin</creatorcontrib><creatorcontrib>Dai, Haowei</creatorcontrib><creatorcontrib>Chen, Keyin</creatorcontrib><creatorcontrib>Wang, Xingqin</creatorcontrib><creatorcontrib>Huang, Ruiwang</creatorcontrib><creatorcontrib>Wei, Xinhua</creatorcontrib><creatorcontrib>Zhang, Ruibin</creatorcontrib><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychological medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jiayuan</au><au>Toulopoulou, Timothea</au><au>Li, Qian</au><au>Niu, Lijing</au><au>Peng, Lanxin</au><au>Dai, Haowei</au><au>Chen, Keyin</au><au>Wang, Xingqin</au><au>Huang, Ruiwang</au><au>Wei, Xinhua</au><au>Zhang, Ruibin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies</atitle><jtitle>Psychological medicine</jtitle><date>2024-11-20</date><risdate>2024</risdate><volume>54</volume><issue>15</issue><spage>1</spage><epage>4082</epage><pages>1-4082</pages><issn>1469-8978</issn><issn>0033-2917</issn><eissn>1469-8978</eissn><abstract>Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.BACKGROUNDPsychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes.We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.METHODSWe examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders.Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.RESULTSStatistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders.Altered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.CONCLUSIONSAltered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>39564744</pmid><doi>10.1017/S0033291724001673</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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title Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies
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