Higher pretreatment 5‐HT1A receptor binding potential in bipolar disorder depression is associated with treatment remission: A naturalistic treatment pilot PET study

Bipolar disorder is a major cause of disability and a high risk for suicide. The pathophysiology of the disorder remains largely unknown. Medication choice for bipolar depression patients involves trial and error. Our group reported previously that brain serotonin 1A (5‐HT1A) receptor binding measured by positron emission tomography (PET) is higher in bipolar depression. We now investigated whether pretreatment 5‐HT1A levels correlates with antidepressant medication outcome. Forty‐one medication‐free DSM‐IV diagnosed, bipolar patients in a major depressive episode had brain PET scans performed using [11C]WAY‐100635 and a metabolite corrected arterial input function. The patients then received naturalistic psychopharmacologic treatment as outpatients and a follow up Hamilton Depression Rating Scale (HDRS) after 3 months of treatment. Patients with 24 item HDRS scores less than 10 were considered to have remitted. A linear mixed effects model was used to compare BPF (binding potential, proportional to the total number of available receptors) in 13 brain regions of interest between remitters and nonremitters. Thirty‐four patients completed 3 months of treatment and ratings; 9 had remitted. Remitters and nonremitters did not differ in age, sex, or recent medication history with serotonergic medications. Remitters had higher [11C]WAY‐100635 BPF across all brain regions compared with nonremitters (P = 0.02). Higher pretreatment brain 5‐HT1A receptor binding was associated with remission after 3 months of pharmacological treatment in bipolar depression. Prospective treatment studies are warranted to determine whether this test predicts outcome of specific types of treatment. Synapse 67:773–778, 2013. © 2013 Wiley Periodicals, Inc.

[1]  D. Kupfer,et al.  Serotonin-1A receptor imaging in recurrent depression: replication and literature review. , 2007, Nuclear medicine and biology.

[2]  Ramin V. Parsey,et al.  Positron Emission Tomography Quantification of Serotonin-1A Receptor Binding in Medication-Free Bipolar Depression , 2009, Biological Psychiatry.

[3]  D. Comings,et al.  A common C-1018G polymorphism in the human 5-HT1A receptor gene. , 1999, Psychiatric genetics.

[4]  R. Parsey,et al.  Higher Serotonin 1A Binding in a Second Major Depression Cohort: Modeling and Reference Region Considerations , 2010, Biological Psychiatry.

[5]  P A Sargent,et al.  Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. , 2000, Archives of general psychiatry.

[6]  Robert B. Innis,et al.  Serotonin-1A receptors in major depression quantified using PET: Controversies, confounds, and recommendations , 2012, NeuroImage.

[7]  I. Ferrier,et al.  Cerebral white matter lesions in bipolar affective disorder: relationship to outcome , 2001, British Journal of Psychiatry.

[8]  Christine DeLorenzo,et al.  Antidepressant Treatment Reduces Serotonin-1A Autoreceptor Binding in Major Depressive Disorder , 2013, Biological Psychiatry.

[9]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[10]  J. Fleiss,et al.  The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. , 1976, Archives of general psychiatry.

[11]  Ramin V. Parsey,et al.  Altered Serotonin 1A Binding in Major Depression: A [carbonyl-C-11]WAY100635 Positron Emission Tomography Study , 2006, Biological Psychiatry.

[12]  J. Calabrese,et al.  Bipolar Depression: Overview and Commentary , 2010, Harvard review of psychiatry.

[13]  V. Arango,et al.  Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. , 2004, The international journal of neuropsychopharmacology.

[14]  C. Montigny,et al.  Role of Somatodendritic 5‐HT Autoreceptors in Modulating 5‐HT Neurotransmission a , 1998, Annals of the New York Academy of Sciences.

[15]  H. Lôo [On bipolar disorder]. , 2008, L'Encephale.

[16]  R. C. Young,et al.  A Rating Scale for Mania: Reliability, Validity and Sensitivity , 1978, British Journal of Psychiatry.

[17]  Victoria Arango,et al.  Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635 , 2002, Brain Research.

[18]  M Slifstein,et al.  Validation and Reproducibility of Measurement of 5-HT1A Receptor Parameters with [carbonyl-11C]WAY-100635 in Humans: Comparison of Arterial and Reference Tissue Input Functions , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  E. C. Harris,et al.  Suicide as an outcome for mental disorders , 1997, British Journal of Psychiatry.

[20]  Victoria Arango,et al.  Regional Heterogeneity of 5-HT1A Receptors in Human Cerebellum as Assessed by Positron Emission Tomography , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  H. Swartz,et al.  The use of antidepressants in bipolar disorder. , 2008, The Journal of clinical psychiatry.

[22]  D. Kupfer,et al.  Pet imaging of serotonin 1A receptor binding in depression , 1999, Biological Psychiatry.

[23]  R Todd Ogden,et al.  Estimation in regression models with externally estimated parameters. , 2005, Biostatistics.

[24]  R. Rosenfeld Patients , 2012, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[25]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[26]  Michael Bauer,et al.  Epidemiology of Bipolar Disorders , 2005, Epilepsia.

[27]  R Todd Ogden,et al.  Higher 5-HT1A Receptor Binding Potential During a Major Depressive Episode Predicts Poor Treatment Response: Preliminary Data from a Naturalistic Study , 2006, Neuropsychopharmacology.

[28]  R. Conley,et al.  Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients. , 2008, Bipolar disorders.

[29]  David Goldman,et al.  Monoamine Oxidase A Genotype Predicts Human Serotonin 1A Receptor Availability In Vivo , 2008, The Journal of Neuroscience.

[30]  M. Weissman,et al.  Cross-national epidemiology of major depression and bipolar disorder. , 1996, JAMA.