A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder
Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth...
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MDPI AG
2022-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/6/1006 |
| _version_ | 1797485488571940864 |
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| author | Duncan C. Honeycutt Melissa P. DelBello Jeffrey R. Strawn Laura B. Ramsey Luis R. Patino Kyle Hinman Jeffrey Welge David J. Miklowitz Booil Jo Thomas J. Blom Kaitlyn M. Bruns Sarah K. Hamill Skoch Nicole Starace Maxwell J. Tallman Manpreet K. Singh |
| author_facet | Duncan C. Honeycutt Melissa P. DelBello Jeffrey R. Strawn Laura B. Ramsey Luis R. Patino Kyle Hinman Jeffrey Welge David J. Miklowitz Booil Jo Thomas J. Blom Kaitlyn M. Bruns Sarah K. Hamill Skoch Nicole Starace Maxwell J. Tallman Manpreet K. Singh |
| author_sort | Duncan C. Honeycutt |
| collection | DOAJ |
| description | Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12–17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, <i>CYP2C19</i> metabolizer phenotype, and <i>HTR2A</i> and <i>SLC6A4</i> genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures. |
| first_indexed | 2024-03-09T23:19:30Z |
| format | Article |
| id | doaj.art-65c3fdc454c04a299a797d8ee926c34a |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T23:19:30Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-65c3fdc454c04a299a797d8ee926c34a2023-11-23T17:29:09ZengMDPI AGJournal of Personalized Medicine2075-44262022-06-01126100610.3390/jpm12061006A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar DisorderDuncan C. Honeycutt0Melissa P. DelBello1Jeffrey R. Strawn2Laura B. Ramsey3Luis R. Patino4Kyle Hinman5Jeffrey Welge6David J. Miklowitz7Booil Jo8Thomas J. Blom9Kaitlyn M. Bruns10Sarah K. Hamill Skoch11Nicole Starace12Maxwell J. Tallman13Manpreet K. Singh14Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADeptartment of Pediatrics Research in Patient Services, Cincinnati Children’s Hospital Medical Center, Pharmacy Research, Cincinnati, OH 45229, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford, CA 94304, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USASemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90024, USADepartment of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford, CA 94304, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford, CA 94304, USADepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford, CA 94304, USAAntidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12–17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, <i>CYP2C19</i> metabolizer phenotype, and <i>HTR2A</i> and <i>SLC6A4</i> genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.https://www.mdpi.com/2075-4426/12/6/1006bipolar riskhyperarousaldepressionanxietyadolescentneuroimaging |
| spellingShingle | Duncan C. Honeycutt Melissa P. DelBello Jeffrey R. Strawn Laura B. Ramsey Luis R. Patino Kyle Hinman Jeffrey Welge David J. Miklowitz Booil Jo Thomas J. Blom Kaitlyn M. Bruns Sarah K. Hamill Skoch Nicole Starace Maxwell J. Tallman Manpreet K. Singh A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder Journal of Personalized Medicine bipolar risk hyperarousal depression anxiety adolescent neuroimaging |
| title | A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder |
| title_full | A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder |
| title_fullStr | A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder |
| title_full_unstemmed | A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder |
| title_short | A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder |
| title_sort | double blind randomized trial to investigate mechanisms of antidepressant related dysfunctional arousal in depressed or anxious youth at familial risk for bipolar disorder |
| topic | bipolar risk hyperarousal depression anxiety adolescent neuroimaging |
| url | https://www.mdpi.com/2075-4426/12/6/1006 |
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