Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study
Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have...
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| Veröffentlicht in: | Journal of psychopharmacology (Oxford) 2024-12, Vol.38 (12), p.1071-1082 |
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| creator | Lukow, Paulina B Lowther, Millie Pike, Alexandra C Yamamori, Yumeya Chavanne, Alice V Gormley, Siobhan Aylward, Jessica McCloud, Tayla Goble, Talya Rodriguez-Sanchez, Julia Tuominen, Ella W Buehler, Sarah K Kirk, Peter Robinson, Oliver J |
| description | Background:
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.
Aims:
To investigate the neural correlates of subchronic antidepressant administration.
Methods:
We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration.
Results:
Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration.
Conclusions:
To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin. |
| doi_str_mv | 10.1177/02698811241286773 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11531087</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_02698811241286773</sage_id><sourcerecordid>3112860663</sourcerecordid><originalsourceid>FETCH-LOGICAL-c306t-2e01e3128cdb97d357d3e67e469933e977a5c7d610d5e5c31daffb7c190543c43</originalsourceid><addsrcrecordid>eNp1kcuO1DAQRS0EYpqBD2CDLLFhk8GOYzthg1ojXtJIbGAdVTuVxKPEbmynpfwDH42jHoaXWFi2qk7dqvIl5DlnV5xr_ZqVqqlrzsuKl7XSWjwgO14pXuiylg_JbssXG3BBnsR4yxhXlZKPyYVoRH7V1Y5838_r0MEEFEyyJ5tWCn3CQONyMGPwzhqK0dgEkz8GmCl0s3U2pgDJeketoyPClMaVnvy0uIQY4hu6p8cRwgzGF_3izIbCRGcYHKasGDDmgDNIbY5ZN9CYlm59Sh71MEV8dndfkq_v3325_ljcfP7w6Xp_UxjBVCpKZBxFXtl0h0Z3QuaDSmOlmkYIbLQGaXSnOOskSiN4B31_0IY3TFbCVOKSvD3rHpfDjJ1Bl9eZ2mPI04S19WDbPzPOju3gTy3nUnBW66zw6k4h-G8LxtTONhqcJnDol9gKvjnClBIZffkXeuuXkL9jo7JzVSVVkyl-pkzwMQbs76fhrN3Mbv8xO9e8-H2N-4qf7mbg6gxEGPBX2_8r_gDAS7Xh</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3124144569</pqid></control><display><type>article</type><title>Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study</title><source>MEDLINE</source><source>SAGE Complete A-Z List</source><creator>Lukow, Paulina B ; Lowther, Millie ; Pike, Alexandra C ; Yamamori, Yumeya ; Chavanne, Alice V ; Gormley, Siobhan ; Aylward, Jessica ; McCloud, Tayla ; Goble, Talya ; Rodriguez-Sanchez, Julia ; Tuominen, Ella W ; Buehler, Sarah K ; Kirk, Peter ; Robinson, Oliver J</creator><creatorcontrib>Lukow, Paulina B ; Lowther, Millie ; Pike, Alexandra C ; Yamamori, Yumeya ; Chavanne, Alice V ; Gormley, Siobhan ; Aylward, Jessica ; McCloud, Tayla ; Goble, Talya ; Rodriguez-Sanchez, Julia ; Tuominen, Ella W ; Buehler, Sarah K ; Kirk, Peter ; Robinson, Oliver J</creatorcontrib><description>Background:
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.
Aims:
To investigate the neural correlates of subchronic antidepressant administration.
Methods:
We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration.
Results:
Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration.
Conclusions:
To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.</description><identifier>ISSN: 0269-8811</identifier><identifier>ISSN: 1461-7285</identifier><identifier>EISSN: 1461-7285</identifier><identifier>DOI: 10.1177/02698811241286773</identifier><identifier>PMID: 39364684</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Amygdala ; Amygdala - diagnostic imaging ; Amygdala - drug effects ; Anxiety disorders ; Brain mapping ; Citalopram ; Citalopram - administration & dosage ; Citalopram - pharmacology ; Cortex (cingulate) ; Cortex (frontal) ; Double-Blind Method ; Escitalopram - administration & dosage ; Escitalopram - pharmacology ; Female ; Functional magnetic resonance imaging ; Healthy Volunteers ; Humans ; Image processing ; Magnetic Resonance Imaging ; Male ; Neural networks ; Neuroimaging ; Neurosciences ; Original Papers ; Placebos ; Prefrontal cortex ; Prefrontal Cortex - diagnostic imaging ; Prefrontal Cortex - drug effects ; Selective Serotonin Reuptake Inhibitors - administration & dosage ; Selective Serotonin Reuptake Inhibitors - pharmacology ; Self-administration ; Serotonin ; Serotonin uptake inhibitors ; Young Adult</subject><ispartof>Journal of psychopharmacology (Oxford), 2024-12, Vol.38 (12), p.1071-1082</ispartof><rights>The Author(s) 2024</rights><rights>The Author(s) 2024 2024 British Association for Psychopharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c306t-2e01e3128cdb97d357d3e67e469933e977a5c7d610d5e5c31daffb7c190543c43</cites><orcidid>0000-0002-6796-9102</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/02698811241286773$$EPDF$$P50$$Gsage$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/02698811241286773$$EHTML$$P50$$Gsage$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39364684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lukow, Paulina B</creatorcontrib><creatorcontrib>Lowther, Millie</creatorcontrib><creatorcontrib>Pike, Alexandra C</creatorcontrib><creatorcontrib>Yamamori, Yumeya</creatorcontrib><creatorcontrib>Chavanne, Alice V</creatorcontrib><creatorcontrib>Gormley, Siobhan</creatorcontrib><creatorcontrib>Aylward, Jessica</creatorcontrib><creatorcontrib>McCloud, Tayla</creatorcontrib><creatorcontrib>Goble, Talya</creatorcontrib><creatorcontrib>Rodriguez-Sanchez, Julia</creatorcontrib><creatorcontrib>Tuominen, Ella W</creatorcontrib><creatorcontrib>Buehler, Sarah K</creatorcontrib><creatorcontrib>Kirk, Peter</creatorcontrib><creatorcontrib>Robinson, Oliver J</creatorcontrib><title>Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study</title><title>Journal of psychopharmacology (Oxford)</title><addtitle>J Psychopharmacol</addtitle><description>Background:
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.
Aims:
To investigate the neural correlates of subchronic antidepressant administration.
Methods:
We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration.
Results:
Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration.
Conclusions:
To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.</description><subject>Adult</subject><subject>Amygdala</subject><subject>Amygdala - diagnostic imaging</subject><subject>Amygdala - drug effects</subject><subject>Anxiety disorders</subject><subject>Brain mapping</subject><subject>Citalopram</subject><subject>Citalopram - administration & dosage</subject><subject>Citalopram - pharmacology</subject><subject>Cortex (cingulate)</subject><subject>Cortex (frontal)</subject><subject>Double-Blind Method</subject><subject>Escitalopram - administration & dosage</subject><subject>Escitalopram - pharmacology</subject><subject>Female</subject><subject>Functional magnetic resonance imaging</subject><subject>Healthy Volunteers</subject><subject>Humans</subject><subject>Image processing</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Neural networks</subject><subject>Neuroimaging</subject><subject>Neurosciences</subject><subject>Original Papers</subject><subject>Placebos</subject><subject>Prefrontal cortex</subject><subject>Prefrontal Cortex - diagnostic imaging</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Selective Serotonin Reuptake Inhibitors - administration & dosage</subject><subject>Selective Serotonin Reuptake Inhibitors - pharmacology</subject><subject>Self-administration</subject><subject>Serotonin</subject><subject>Serotonin uptake inhibitors</subject><subject>Young Adult</subject><issn>0269-8811</issn><issn>1461-7285</issn><issn>1461-7285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><recordid>eNp1kcuO1DAQRS0EYpqBD2CDLLFhk8GOYzthg1ojXtJIbGAdVTuVxKPEbmynpfwDH42jHoaXWFi2qk7dqvIl5DlnV5xr_ZqVqqlrzsuKl7XSWjwgO14pXuiylg_JbssXG3BBnsR4yxhXlZKPyYVoRH7V1Y5838_r0MEEFEyyJ5tWCn3CQONyMGPwzhqK0dgEkz8GmCl0s3U2pgDJeketoyPClMaVnvy0uIQY4hu6p8cRwgzGF_3izIbCRGcYHKasGDDmgDNIbY5ZN9CYlm59Sh71MEV8dndfkq_v3325_ljcfP7w6Xp_UxjBVCpKZBxFXtl0h0Z3QuaDSmOlmkYIbLQGaXSnOOskSiN4B31_0IY3TFbCVOKSvD3rHpfDjJ1Bl9eZ2mPI04S19WDbPzPOju3gTy3nUnBW66zw6k4h-G8LxtTONhqcJnDol9gKvjnClBIZffkXeuuXkL9jo7JzVSVVkyl-pkzwMQbs76fhrN3Mbv8xO9e8-H2N-4qf7mbg6gxEGPBX2_8r_gDAS7Xh</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Lukow, Paulina B</creator><creator>Lowther, Millie</creator><creator>Pike, Alexandra C</creator><creator>Yamamori, Yumeya</creator><creator>Chavanne, Alice V</creator><creator>Gormley, Siobhan</creator><creator>Aylward, Jessica</creator><creator>McCloud, Tayla</creator><creator>Goble, Talya</creator><creator>Rodriguez-Sanchez, Julia</creator><creator>Tuominen, Ella W</creator><creator>Buehler, Sarah K</creator><creator>Kirk, Peter</creator><creator>Robinson, Oliver J</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><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>7TK</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6796-9102</orcidid></search><sort><creationdate>20241201</creationdate><title>Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study</title><author>Lukow, Paulina B ; Lowther, Millie ; Pike, Alexandra C ; Yamamori, Yumeya ; Chavanne, Alice V ; Gormley, Siobhan ; Aylward, Jessica ; McCloud, Tayla ; Goble, Talya ; Rodriguez-Sanchez, Julia ; Tuominen, Ella W ; Buehler, Sarah K ; Kirk, Peter ; Robinson, Oliver J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c306t-2e01e3128cdb97d357d3e67e469933e977a5c7d610d5e5c31daffb7c190543c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Amygdala</topic><topic>Amygdala - diagnostic imaging</topic><topic>Amygdala - drug effects</topic><topic>Anxiety disorders</topic><topic>Brain mapping</topic><topic>Citalopram</topic><topic>Citalopram - administration & dosage</topic><topic>Citalopram - pharmacology</topic><topic>Cortex (cingulate)</topic><topic>Cortex (frontal)</topic><topic>Double-Blind Method</topic><topic>Escitalopram - administration & dosage</topic><topic>Escitalopram - pharmacology</topic><topic>Female</topic><topic>Functional magnetic resonance imaging</topic><topic>Healthy Volunteers</topic><topic>Humans</topic><topic>Image processing</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Neural networks</topic><topic>Neuroimaging</topic><topic>Neurosciences</topic><topic>Original Papers</topic><topic>Placebos</topic><topic>Prefrontal cortex</topic><topic>Prefrontal Cortex - diagnostic imaging</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Selective Serotonin Reuptake Inhibitors - administration & dosage</topic><topic>Selective Serotonin Reuptake Inhibitors - pharmacology</topic><topic>Self-administration</topic><topic>Serotonin</topic><topic>Serotonin uptake inhibitors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lukow, Paulina B</creatorcontrib><creatorcontrib>Lowther, Millie</creatorcontrib><creatorcontrib>Pike, Alexandra C</creatorcontrib><creatorcontrib>Yamamori, Yumeya</creatorcontrib><creatorcontrib>Chavanne, Alice V</creatorcontrib><creatorcontrib>Gormley, Siobhan</creatorcontrib><creatorcontrib>Aylward, Jessica</creatorcontrib><creatorcontrib>McCloud, Tayla</creatorcontrib><creatorcontrib>Goble, Talya</creatorcontrib><creatorcontrib>Rodriguez-Sanchez, Julia</creatorcontrib><creatorcontrib>Tuominen, Ella W</creatorcontrib><creatorcontrib>Buehler, Sarah K</creatorcontrib><creatorcontrib>Kirk, Peter</creatorcontrib><creatorcontrib>Robinson, Oliver J</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of psychopharmacology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lukow, Paulina B</au><au>Lowther, Millie</au><au>Pike, Alexandra C</au><au>Yamamori, Yumeya</au><au>Chavanne, Alice V</au><au>Gormley, Siobhan</au><au>Aylward, Jessica</au><au>McCloud, Tayla</au><au>Goble, Talya</au><au>Rodriguez-Sanchez, Julia</au><au>Tuominen, Ella W</au><au>Buehler, Sarah K</au><au>Kirk, Peter</au><au>Robinson, Oliver J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study</atitle><jtitle>Journal of psychopharmacology (Oxford)</jtitle><addtitle>J Psychopharmacol</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>38</volume><issue>12</issue><spage>1071</spage><epage>1082</epage><pages>1071-1082</pages><issn>0269-8811</issn><issn>1461-7285</issn><eissn>1461-7285</eissn><abstract>Background:
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.
Aims:
To investigate the neural correlates of subchronic antidepressant administration.
Methods:
We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration.
Results:
Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration.
Conclusions:
To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>39364684</pmid><doi>10.1177/02698811241286773</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-6796-9102</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Amygdala Amygdala - diagnostic imaging Amygdala - drug effects Anxiety disorders Brain mapping Citalopram Citalopram - administration & dosage Citalopram - pharmacology Cortex (cingulate) Cortex (frontal) Double-Blind Method Escitalopram - administration & dosage Escitalopram - pharmacology Female Functional magnetic resonance imaging Healthy Volunteers Humans Image processing Magnetic Resonance Imaging Male Neural networks Neuroimaging Neurosciences Original Papers Placebos Prefrontal cortex Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - drug effects Selective Serotonin Reuptake Inhibitors - administration & dosage Selective Serotonin Reuptake Inhibitors - pharmacology Self-administration Serotonin Serotonin uptake inhibitors Young Adult |
| title | Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study |
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