Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study
Rationale Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial...
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| Veröffentlicht in: | Psychopharmacology 2016-10, Vol.233 (21-22), p.3803-3813 |
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| creator | Fervaha, Gagan Caravaggio, Fernando Mamo, David C. Mulsant, Benoit H. Pollock, Bruce G. Nakajima, Shinichiro Gerretsen, Philip Rajji, Tarek K. Mar, Wanna Iwata, Yusuke Plitman, Eric Chung, Jun Ku Remington, Gary Graff-Guerrero, Ariel |
| description | Rationale
Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial.
Objective
The objective of this study was to examine the relationship between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptoms in patients with schizophrenia.
Methods
Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [
11
C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose.
Results
No significant relationship was found between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship.
Conclusions
Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined. |
| doi_str_mv | 10.1007/s00213-016-4415-6 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5065392</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A470683669</galeid><sourcerecordid>A470683669</sourcerecordid><originalsourceid>FETCH-LOGICAL-c636t-c7ff3f605dfdad66c2df8a68b1b37b3d4b315a7276a335771c39dd45c49cb7793</originalsourceid><addsrcrecordid>eNqNkstu1DAUhiMEokPhAdggS2zYpPXdCQukquUmjcQG1pZjOxmXxA520iq8Td8UhylDi0DCXjiKv_PJPv6L4jmCJwhCcZogxIiUEPGSUsRK_qDYIEpwiaHAD4sNhISUBLHqqHiS0iXMg1b0cXGEBWOipvWmuNkq_RWEFqiUgnZqcsGDxk7X1npgwqgG523snAbKT6oL3qUhfxrgbZfhKwvSMoxTGBJwHiS9c9_DuIvWO_UaKDCG5KaYlXZwKa3ujIYuqnG3HPTgAp8SEK22WRRB0HoeldcLSNNslqfFo1b1yT67XY-LL-_efj7_UG4_vf94frYtNSd8KrVoW9JyyExrlOFcY9NWilcNaohoiKFNboQSWHBFCBMCaVIbQ5mmtW6EqMlx8WbvHedmsEZbP0XVyzG6QcVFBuXk_R3vdrILV5JBzkiNs-DVrSCGb7NNk8x31rbvlbdhThJVlFPICRH_gRJGEcF8PdbLP9DLMEefO5EpXGHKGat-U53qrXS-DfmIepXKMyogrwj_6Tr5C5Wnyc-jg7ety__vFaB9gY4hpWjbQzsQlGsE5T6CMkdQrhGUPNe8uNvHQ8WvzGUA74GUt3xn450b_dP6A6n16aw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1828246558</pqid></control><display><type>article</type><title>Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Fervaha, Gagan ; Caravaggio, Fernando ; Mamo, David C. ; Mulsant, Benoit H. ; Pollock, Bruce G. ; Nakajima, Shinichiro ; Gerretsen, Philip ; Rajji, Tarek K. ; Mar, Wanna ; Iwata, Yusuke ; Plitman, Eric ; Chung, Jun Ku ; Remington, Gary ; Graff-Guerrero, Ariel</creator><creatorcontrib>Fervaha, Gagan ; Caravaggio, Fernando ; Mamo, David C. ; Mulsant, Benoit H. ; Pollock, Bruce G. ; Nakajima, Shinichiro ; Gerretsen, Philip ; Rajji, Tarek K. ; Mar, Wanna ; Iwata, Yusuke ; Plitman, Eric ; Chung, Jun Ku ; Remington, Gary ; Graff-Guerrero, Ariel</creatorcontrib><description>Rationale
Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial.
Objective
The objective of this study was to examine the relationship between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptoms in patients with schizophrenia.
Methods
Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [
11
C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose.
Results
No significant relationship was found between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship.
Conclusions
Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-016-4415-6</identifier><identifier>PMID: 27557949</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Antipsychotic Agents - administration & dosage ; Antipsychotic drugs ; Biomedical and Life Sciences ; Biomedicine ; Brain - diagnostic imaging ; Brain - metabolism ; Carbon Radioisotopes ; Cross-Sectional Studies ; Dopamine ; Dopamine Antagonists ; Dopamine receptors ; Dose-Response Relationship, Drug ; Drug therapy ; Female ; Health aspects ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Neurosciences ; Original Investigation ; Patient outcomes ; Pharmacology/Toxicology ; Positron-Emission Tomography ; Prospective Studies ; Psychiatry ; Psychopharmacology ; Psychotropic drugs ; Raclopride ; Radiopharmaceuticals ; Receptors, Dopamine D2 - metabolism ; Receptors, Dopamine D3 - metabolism ; Schizophrenia ; Schizophrenia - drug therapy ; Schizophrenic Psychology ; Side effects</subject><ispartof>Psychopharmacology, 2016-10, Vol.233 (21-22), p.3803-3813</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><rights>COPYRIGHT 2016 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c636t-c7ff3f605dfdad66c2df8a68b1b37b3d4b315a7276a335771c39dd45c49cb7793</citedby><cites>FETCH-LOGICAL-c636t-c7ff3f605dfdad66c2df8a68b1b37b3d4b315a7276a335771c39dd45c49cb7793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-016-4415-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-016-4415-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27557949$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fervaha, Gagan</creatorcontrib><creatorcontrib>Caravaggio, Fernando</creatorcontrib><creatorcontrib>Mamo, David C.</creatorcontrib><creatorcontrib>Mulsant, Benoit H.</creatorcontrib><creatorcontrib>Pollock, Bruce G.</creatorcontrib><creatorcontrib>Nakajima, Shinichiro</creatorcontrib><creatorcontrib>Gerretsen, Philip</creatorcontrib><creatorcontrib>Rajji, Tarek K.</creatorcontrib><creatorcontrib>Mar, Wanna</creatorcontrib><creatorcontrib>Iwata, Yusuke</creatorcontrib><creatorcontrib>Plitman, Eric</creatorcontrib><creatorcontrib>Chung, Jun Ku</creatorcontrib><creatorcontrib>Remington, Gary</creatorcontrib><creatorcontrib>Graff-Guerrero, Ariel</creatorcontrib><title>Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial.
Objective
The objective of this study was to examine the relationship between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptoms in patients with schizophrenia.
Methods
Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [
11
C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose.
Results
No significant relationship was found between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship.
Conclusions
Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined.</description><subject>Adult</subject><subject>Antipsychotic Agents - administration & dosage</subject><subject>Antipsychotic drugs</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Carbon Radioisotopes</subject><subject>Cross-Sectional Studies</subject><subject>Dopamine</subject><subject>Dopamine Antagonists</subject><subject>Dopamine receptors</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Patient outcomes</subject><subject>Pharmacology/Toxicology</subject><subject>Positron-Emission Tomography</subject><subject>Prospective Studies</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychotropic drugs</subject><subject>Raclopride</subject><subject>Radiopharmaceuticals</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Receptors, Dopamine D3 - metabolism</subject><subject>Schizophrenia</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenic Psychology</subject><subject>Side effects</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkstu1DAUhiMEokPhAdggS2zYpPXdCQukquUmjcQG1pZjOxmXxA520iq8Td8UhylDi0DCXjiKv_PJPv6L4jmCJwhCcZogxIiUEPGSUsRK_qDYIEpwiaHAD4sNhISUBLHqqHiS0iXMg1b0cXGEBWOipvWmuNkq_RWEFqiUgnZqcsGDxk7X1npgwqgG523snAbKT6oL3qUhfxrgbZfhKwvSMoxTGBJwHiS9c9_DuIvWO_UaKDCG5KaYlXZwKa3ujIYuqnG3HPTgAp8SEK22WRRB0HoeldcLSNNslqfFo1b1yT67XY-LL-_efj7_UG4_vf94frYtNSd8KrVoW9JyyExrlOFcY9NWilcNaohoiKFNboQSWHBFCBMCaVIbQ5mmtW6EqMlx8WbvHedmsEZbP0XVyzG6QcVFBuXk_R3vdrILV5JBzkiNs-DVrSCGb7NNk8x31rbvlbdhThJVlFPICRH_gRJGEcF8PdbLP9DLMEefO5EpXGHKGat-U53qrXS-DfmIepXKMyogrwj_6Tr5C5Wnyc-jg7ety__vFaB9gY4hpWjbQzsQlGsE5T6CMkdQrhGUPNe8uNvHQ8WvzGUA74GUt3xn450b_dP6A6n16aw</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Fervaha, Gagan</creator><creator>Caravaggio, Fernando</creator><creator>Mamo, David C.</creator><creator>Mulsant, Benoit H.</creator><creator>Pollock, Bruce G.</creator><creator>Nakajima, Shinichiro</creator><creator>Gerretsen, Philip</creator><creator>Rajji, Tarek K.</creator><creator>Mar, Wanna</creator><creator>Iwata, Yusuke</creator><creator>Plitman, Eric</creator><creator>Chung, Jun Ku</creator><creator>Remington, Gary</creator><creator>Graff-Guerrero, Ariel</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161001</creationdate><title>Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study</title><author>Fervaha, Gagan ; Caravaggio, Fernando ; Mamo, David C. ; Mulsant, Benoit H. ; Pollock, Bruce G. ; Nakajima, Shinichiro ; Gerretsen, Philip ; Rajji, Tarek K. ; Mar, Wanna ; Iwata, Yusuke ; Plitman, Eric ; Chung, Jun Ku ; Remington, Gary ; Graff-Guerrero, Ariel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c636t-c7ff3f605dfdad66c2df8a68b1b37b3d4b315a7276a335771c39dd45c49cb7793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Antipsychotic Agents - administration & dosage</topic><topic>Antipsychotic drugs</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Carbon Radioisotopes</topic><topic>Cross-Sectional Studies</topic><topic>Dopamine</topic><topic>Dopamine Antagonists</topic><topic>Dopamine receptors</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Patient outcomes</topic><topic>Pharmacology/Toxicology</topic><topic>Positron-Emission Tomography</topic><topic>Prospective Studies</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychotropic drugs</topic><topic>Raclopride</topic><topic>Radiopharmaceuticals</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Receptors, Dopamine D3 - metabolism</topic><topic>Schizophrenia</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenic Psychology</topic><topic>Side effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fervaha, Gagan</creatorcontrib><creatorcontrib>Caravaggio, Fernando</creatorcontrib><creatorcontrib>Mamo, David C.</creatorcontrib><creatorcontrib>Mulsant, Benoit H.</creatorcontrib><creatorcontrib>Pollock, Bruce G.</creatorcontrib><creatorcontrib>Nakajima, Shinichiro</creatorcontrib><creatorcontrib>Gerretsen, Philip</creatorcontrib><creatorcontrib>Rajji, Tarek K.</creatorcontrib><creatorcontrib>Mar, Wanna</creatorcontrib><creatorcontrib>Iwata, Yusuke</creatorcontrib><creatorcontrib>Plitman, Eric</creatorcontrib><creatorcontrib>Chung, Jun Ku</creatorcontrib><creatorcontrib>Remington, Gary</creatorcontrib><creatorcontrib>Graff-Guerrero, Ariel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fervaha, Gagan</au><au>Caravaggio, Fernando</au><au>Mamo, David C.</au><au>Mulsant, Benoit H.</au><au>Pollock, Bruce G.</au><au>Nakajima, Shinichiro</au><au>Gerretsen, Philip</au><au>Rajji, Tarek K.</au><au>Mar, Wanna</au><au>Iwata, Yusuke</au><au>Plitman, Eric</au><au>Chung, Jun Ku</au><au>Remington, Gary</au><au>Graff-Guerrero, Ariel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>233</volume><issue>21-22</issue><spage>3803</spage><epage>3813</epage><pages>3803-3813</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial.
Objective
The objective of this study was to examine the relationship between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptoms in patients with schizophrenia.
Methods
Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [
11
C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose.
Results
No significant relationship was found between antipsychotic-related dopamine D
2/3
receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship.
Conclusions
Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27557949</pmid><doi>10.1007/s00213-016-4415-6</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0033-3158 1432-2072 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adult Antipsychotic Agents - administration & dosage Antipsychotic drugs Biomedical and Life Sciences Biomedicine Brain - diagnostic imaging Brain - metabolism Carbon Radioisotopes Cross-Sectional Studies Dopamine Dopamine Antagonists Dopamine receptors Dose-Response Relationship, Drug Drug therapy Female Health aspects Humans Longitudinal Studies Male Middle Aged Neurosciences Original Investigation Patient outcomes Pharmacology/Toxicology Positron-Emission Tomography Prospective Studies Psychiatry Psychopharmacology Psychotropic drugs Raclopride Radiopharmaceuticals Receptors, Dopamine D2 - metabolism Receptors, Dopamine D3 - metabolism Schizophrenia Schizophrenia - drug therapy Schizophrenic Psychology Side effects |
| title | Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study |
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