title: Reduced post-synaptic serotonin type 1A receptor binding in bipolar depression.
abstract: Multiple lines of evidence suggest that serotonin type 1A (5-HT(1A)) receptor dysfunction is involved in the pathophysiology of mood disorders, and that alterations in 5-HT(1A) receptor function play a role in the mechanisms of antidepressant and mood stabilizer treatment. The literature is in disagreement, however, as to whether 5-HT(1A) receptor binding abnormalities exist in bipolar disorder (BD). We acquired PET images of 5-HT(1A) receptor binding in 26 unmedicated BD subjects and 37 healthy controls using [¹⁸F]FCWAY, a highly selective 5-HT(1A) receptor radio-ligand. The mean 5-HT(1A) receptor binding potential (BP(P)) was significantly lower in BD subjects compared to controls in cortical regions where 5-HT(1A) receptors are expressed post-synaptically, most prominently in the mesiotemporal cortex. Post-hoc assessments involving other receptor specific binding parameters suggested that this difference particularly affected the females with BD. The mean BPP did not differ between groups in the raphe nucleus, however, where 5-HT(1A) receptors are predominantly expressed pre-synaptically. Across subjects the BPP in the mesiotemporal cortex was inversely correlated with trough plasma cortisol levels, consistent with preclinical literature indicating that hippocampal 5-HT(1A) receptor expression is inhibited by glucocorticoid receptor stimulation. These findings suggest that 5-HT(1A) receptor binding is abnormally reduced in BD, and this abnormality may particularly involve the postsynaptic 5-HT(1A) receptor system of individuals with a tendency toward cortisol hypersecretion.
authors: National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, NIMH, NIH, Bethesda, MD 20892-1030, USA. nugenta@mail.nih.gov
authors: Allison C
authors: AC
authors: Nugent
authors: Earle E
authors: EE
authors: Bain
authors: Paul J
authors: PJ
authors: Carlson
authors: Alexander
authors: A
authors: Neumeister
authors: Omer
authors: O
authors: Bonne
authors: Richard E
authors: RE
authors: Carson
authors: William
authors: W
authors: Eckelman
authors: Peter
authors: P
authors: Herscovitch
authors: Carlos A
authors: CA
authors: Zarate
authors: Dennis S
authors: DS
authors: Charney
authors: Wayne C
authors: WC
authors: Drevets
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism / Q000503:physiopathology; D000308:Adrenocortical Hyperfunction / Q000503:physiopathology; D000328:Adult; D001714:Bipolar Disorder / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D049268:Positron-Emission Tomography; D057907:Post-Synaptic Density / Q000378:metabolism*; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: C583518:HTR1A protein, human; D009419:Nerve Tissue Proteins; D044282:Receptor, Serotonin, 5-HT1A; D006854:Hydrocortisone
keywords: ((18)F)FCWAY; 5-HT1A receptor; Bipolar disorder; Positron-emission tomography