The HPA axis in bipolar disorder: Systematic review and meta-analysis
•Bipolar disorder is associated with state and trait hyperactivity of the HPA axis.•Abnormalities of glucocorticoid signaling are found in several key brain areas.•Cortisol levels are associated with structural and functional neuroimaging indices in BD.•HPA axis dysregulation is not a endophenotype...
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| Published in | Psychoneuroendocrinology Vol. 63; pp. 327 - 342 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.01.2016
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| Subjects | |
| Online Access | Get full text |
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| Abstract | •Bipolar disorder is associated with state and trait hyperactivity of the HPA axis.•Abnormalities of glucocorticoid signaling are found in several key brain areas.•Cortisol levels are associated with structural and functional neuroimaging indices in BD.•HPA axis dysregulation is not a endophenotype of bipolar disorder.•HPA axis dysfunction can increase the risk of relapses and cognitive deterioration.
To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic–Pituitary–Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD).
Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD.
Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants’ age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD.
BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD. |
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| AbstractList | To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD).
Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD.
Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants' age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD.
BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD. •Bipolar disorder is associated with state and trait hyperactivity of the HPA axis.•Abnormalities of glucocorticoid signaling are found in several key brain areas.•Cortisol levels are associated with structural and functional neuroimaging indices in BD.•HPA axis dysregulation is not a endophenotype of bipolar disorder.•HPA axis dysfunction can increase the risk of relapses and cognitive deterioration. To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic–Pituitary–Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants’ age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD. Highlights • Bipolar disorder is associated with state and trait hyperactivity of the HPA axis. • Abnormalities of glucocorticoid signaling are found in several key brain areas. • Cortisol levels are associated with structural and functional neuroimaging indices in BD. • HPA axis dysregulation is not a endophenotype of bipolar disorder. • HPA axis dysfunction can increase the risk of relapses and cognitive deterioration. |
| Author | Antonioli, Marco Perna, Giampaolo Amore, Mario Pompili, Maurizio Pariante, Carmine Masotti, Mattia Patti, Sara Mondelli, Valeria Prestia, Davide Serafini, Gianluca Olivieri, Benedetta Belvederi Murri, Martino Vassallo, Linda Arzani, Costanza Respino, Matteo |
| Author_xml | – sequence: 1 givenname: Martino orcidid: 0000-0002-7262-3528 surname: Belvederi Murri fullname: Belvederi Murri, Martino email: martino.belvederi@gmail.com organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 2 givenname: Davide surname: Prestia fullname: Prestia, Davide organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 3 givenname: Valeria surname: Mondelli fullname: Mondelli, Valeria organization: Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King’s College London, London, UK – sequence: 4 givenname: Carmine surname: Pariante fullname: Pariante, Carmine organization: Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King’s College London, London, UK – sequence: 5 givenname: Sara surname: Patti fullname: Patti, Sara organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 6 givenname: Benedetta surname: Olivieri fullname: Olivieri, Benedetta organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 7 givenname: Costanza surname: Arzani fullname: Arzani, Costanza organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 8 givenname: Mattia surname: Masotti fullname: Masotti, Mattia organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 9 givenname: Matteo surname: Respino fullname: Respino, Matteo organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 10 givenname: Marco surname: Antonioli fullname: Antonioli, Marco organization: Section of Psychiatry, Department of Neuroscience and Infant-Maternal Science, University of Sassari, Italy – sequence: 11 givenname: Linda surname: Vassallo fullname: Vassallo, Linda organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 12 givenname: Gianluca surname: Serafini fullname: Serafini, Gianluca organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy – sequence: 13 givenname: Giampaolo surname: Perna fullname: Perna, Giampaolo organization: San Benedetto Hospital, Hermanas Hospitalarias, Department of Clinical Neuroscience, Albese con Cassano, Como, Italy – sequence: 14 givenname: Maurizio surname: Pompili fullname: Pompili, Maurizio organization: Suicide Prevention Center, Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant’Andrea Hospital, Sapienza University of Rome, Italy – sequence: 15 givenname: Mario surname: Amore fullname: Amore, Mario organization: Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26547798$$D View this record in MEDLINE/PubMed |
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| Snippet | •Bipolar disorder is associated with state and trait hyperactivity of the HPA axis.•Abnormalities of glucocorticoid signaling are found in several key brain... Highlights • Bipolar disorder is associated with state and trait hyperactivity of the HPA axis. • Abnormalities of glucocorticoid signaling are found in... To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology... |
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| SubjectTerms | Adrenocorticotropic Hormone - metabolism Bipolar disorder Bipolar Disorder - metabolism Bipolar Disorder - physiopathology Case-Control Studies Corticotropin-Releasing Hormone - metabolism Cortisol Depression Endocrinology & Metabolism Glucocorticoid receptor HPA Axis Humans Hydrocortisone - metabolism Hypothalamo-Hypophyseal System - metabolism Hypothalamo-Hypophyseal System - physiopathology Mania Pituitary-Adrenal System - metabolism Pituitary-Adrenal System - physiopathology Psychiatry |
| Title | The HPA axis in bipolar disorder: Systematic review and meta-analysis |
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