Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions.

Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.

[1]  Rupert Lanzenberger,et al.  FMRI reveals functional cortex in a case of inconclusive Wada testing , 2005, Clinical Neurology and Neurosurgery.

[2]  Dirk H. Hellhammer,et al.  Morningness and eveningness: The free cortisol rise after awakening in “early birds” and “night owls” , 2006, Biological Psychology.

[3]  F. Holsboer,et al.  Stress and the brain: from adaptation to disease , 2005, Nature Reviews Neuroscience.

[4]  V. Kallen,et al.  Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder , 2008, Depression and anxiety.

[5]  N. Kushwaha,et al.  Heterodimerization of Mineralocorticoid and Glucocorticoid Receptors at a Novel Negative Response Element of the 5-HT1A Receptor Gene* , 2001, The Journal of Biological Chemistry.

[6]  R. Lanz,et al.  Nuclear receptor coregulators: cellular and molecular biology. , 1999, Endocrine reviews.

[7]  Ralph Myers,et al.  Assessment of Spatial Normalization of PET Ligand Images Using Ligand-Specific Templates , 1999, NeuroImage.

[8]  W. Drevets,et al.  No change in serotonin type 1A receptor binding in patients with posttraumatic stress disorder. , 2005, The American journal of psychiatry.

[9]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[10]  Rupert Lanzenberger,et al.  Preparation and radiosynthesis of [18F]FE@CFN (2-[18F]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate): a potential μ-opioid receptor imaging agent , 2007 .

[11]  F. Holsboer,et al.  Psychological Stress Increases Hippocampal Mineralocorticoid Receptor Levels: Involvement of Corticotropin-Releasing Hormone , 2001, The Journal of Neuroscience.

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

[13]  G. Heinze,et al.  Binding kinetics of 123I[ADAM] in healthy controls: a selective SERT radioligand. , 2007, The international journal of neuropsychopharmacology.

[14]  Rupert Lanzenberger,et al.  Correlations and anticorrelations in resting-state functional connectivity MRI: A quantitative comparison of preprocessing strategies , 2009, NeuroImage.

[15]  René Hen,et al.  5-HT1A Autoreceptor Levels Determine Vulnerability to Stress and Response to Antidepressants , 2010, Neuron.

[16]  Roger N. Gunn,et al.  A Database of [11C]WAY-100635 Binding to 5-HT1A Receptors in Normal Male Volunteers: Normative Data and Relationship to Methodological, Demographic, Physiological, and Behavioral Variables , 2002, NeuroImage.

[17]  Laurent Descarries,et al.  Acute Treatment with the Antidepressant Fluoxetine Internalizes 5-HT1A Autoreceptors and Reduces the In Vivo Binding of the PET Radioligand [18F]MPPF in the Nucleus Raphe Dorsalis of Rat , 2004, The Journal of Neuroscience.

[18]  Bruce S. McEwen,et al.  The neurobiology of stress: from serendipity to clinical relevance. , 2000, Brain research.

[19]  Daniel Tranel,et al.  Circadian regulation of cortisol after hippocampal damage in humans , 2004, Biological Psychiatry.

[20]  F. Holsboer,et al.  Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress , 2003, Nature Neuroscience.

[21]  B. Pitt.  Psychopharmacology , 1968, Mental Health.

[22]  Wolfgang Grodd,et al.  Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia , 1999, Biological Psychiatry.

[23]  P. Celada,et al.  Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. , 2004, Cerebral cortex.

[24]  S. Kasper.  Social phobia: the nature of the disorder. , 1998, Journal of affective disorders.

[25]  S. Rauch,et al.  A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. , 2005, Archives of general psychiatry.

[26]  I. Lucki,et al.  Abnormal salivary cortisol levels in social phobic patients in response to acute psychological but not physical stress , 2001, Biological Psychiatry.

[27]  L. Nics,et al.  Radiosynthesis of a novel potential adenosine A3 receptor ligand, 5-ethyl 2,4-diethyl-3-((2-[18F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate ([18F]FE@SUPPY:2) , 2009 .

[28]  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.

[29]  S Kasper,et al.  Influence of escitalopram treatment on 5-HT1A receptor binding in limbic regions in patients with anxiety disorders , 2009, Molecular Psychiatry.

[30]  Shitij Kapur,et al.  Serotonin 5-HT1A Receptor Binding Potential Declines with Age as Measured by [11C]WAY-100635 and PET , 2001, Neuropsychopharmacology.

[31]  Rupert Lanzenberger,et al.  A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease , 2006, Clinical pharmacology and therapeutics.

[32]  N. Akaike,et al.  Role of presynaptic 5-HT1A and 5-HT3 receptors in modulation of synaptic GABA transmission in dissociated rat basolateral amygdala neurons. , 2002, Life sciences.

[33]  O. Meijer,et al.  Brain mineralocorticoid receptors and centrally regulated functions. , 2000, Kidney international.

[34]  R Dudczak,et al.  Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications. , 2009, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[35]  P. Cowen,et al.  Increased salivary cortisol after waking in depression , 2005, Psychopharmacology.

[36]  Rupert Lanzenberger,et al.  Light-dependent alteration of serotonin-1A receptor binding in cortical and subcortical limbic regions in the human brain , 2012, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[37]  Rupert Lanzenberger,et al.  The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-11C]WAY-100635 , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[38]  A. Steiger,et al.  Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression , 2003, Journal of clinical psychopharmacology.

[39]  O. Meijer,et al.  A Role for the Mineralocorticoid Receptor in a Rapid and Transient Suppression of Hippocampal 5‐HT1A Receptor mRNA by Corticosterone , 1995, Journal of neuroendocrinology.

[40]  Rupert Lanzenberger,et al.  Simple and fully automated preparation of [carbonyl-11C]WAY-100635 , 2007 .

[41]  R. P. Maguire,et al.  Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  Rupert Lanzenberger,et al.  The Serotonin-1A Receptor in Anxiety Disorders , 2009, Biological Psychiatry.

[43]  H. Akil,et al.  Mineralocorticoid receptor function in major depression. , 2003, Archives of general psychiatry.

[44]  H Fischer,et al.  Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. , 2001, The American journal of psychiatry.

[45]  C. Otte,et al.  Mineralocorticoid Receptor-Mediated Inhibition of the Hypothalamic-Pituitary-Adrenal Axis in Aged Humans , 2003 .

[46]  Siegfried Kasper,et al.  Lateralization of the serotonin-1A receptor distribution in language areas revealed by PET , 2009, NeuroImage.

[47]  Tessa J. Roseboom,et al.  Depression and anxiety: Associations with biological and perceived stress reactivity to a psychological stress protocol in a middle-aged population , 2010, Psychoneuroendocrinology.

[48]  C. Spielberger,et al.  Psychometric properties of the STAI: a reply to Ramanaiah, Franzen, and Schill. , 1984, Journal of personality assessment.

[49]  S. Fuchs,et al.  5-Hydroxytryptamine 1A Receptors, Major Depression, and Suicidal Behavior , 2005, Biological Psychiatry.

[50]  D. Rubinow,et al.  Sex differences in expression of serotonin receptors (subtypes 1A and 2A) in rat brain: a possible role of testosterone , 1999, Neuroscience.

[51]  Juha Markkula,et al.  Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. , 2008, The international journal of neuropsychopharmacology.

[52]  S. Kasper,et al.  [Efficacy of antipsychotic augmentation therapy in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomised, placebo-controlled trials]. , 2011, Fortschritte der Neurologie-Psychiatrie.

[53]  U. Habel,et al.  FMRI of the Emotions: Towards an Improved Understanding of Amygdala Function , 2005 .

[54]  C. McKittrick,et al.  Decreased 5-HT1A and increased 5-HT2A receptor binding after chronic corticosterone associated with a behavioural indication of depression but not anxiety , 1997, Psychoneuroendocrinology.

[55]  S. Claes,et al.  Hypothalamic-pituitary-adrenal reactivity in prepubertal children with social phobia. , 2008, Journal of affective disorders.

[56]  I. Lucki,et al.  5-HT1A receptor function in major depressive disorder , 2009, Progress in Neurobiology.

[57]  Paul J. Harrison,et al.  Increase of 5-HT7 (serotonin-7) and 5-HT1A (serotonin-1A) receptor mRNA expression in rat hippocampus after adrenalectomy , 1997, Psychopharmacology.

[58]  Pia Baldinger,et al.  Imaging treatment effects in depression , 2012, Reviews in the neurosciences.

[59]  Siegfried Kasper,et al.  Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: A randomized cross-over study , 2010, NeuroImage.

[60]  D. C. Howell.  Statistical Methods for Psychology , 1987 .

[61]  B. McEwen,et al.  Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. , 1991, Neuroendocrinology.

[62]  森本 昌史.  Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain : An immunohistochemical and in situ hybridization study , 1997 .

[63]  P. Cowen,et al.  Drug action at the 5-HT(1A) receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-(11)C]WAY-100635. , 2000, Nuclear medicine and biology.

[64]  Siegfried Kasper,et al.  Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain , 2010, NeuroImage.

[65]  Amir Reza Tahamtan,et al.  Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[66]  Robert B. Innis,et al.  Development and Reliability of a Method for Using Magnetic Resonance Imaging for the Definition of Regions of Interest for Positron Emission Tomography. , 1998, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[67]  Daniela Berardi.  Statement of interest , 2002, Description Logics.

[68]  S Kasper,et al.  Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment. , 2000, Journal of affective disorders.

[69]  C. Halldin,et al.  Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain , 2004, Human brain mapping.

[70]  Serotonin receptor knockouts: a moody subject. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Pearce,et al.  Transcriptional Repression of the 5‐HT1A Receptor Promoter by Corticosterone Via Mineralocorticoid Receptors Depends on the Cellular Context , 2000, Journal of neuroendocrinology.

[72]  O. Meijer,et al.  Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteroid receptor diversity. , 1998, Critical reviews in neurobiology.

[73]  E. Setiawan,et al.  Developmental regulation of 5-HT1A receptor mRNA in the fetal limbic system: response to antenatal glucocorticoid. , 2004, Brain research. Developmental brain research.

[74]  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.

[75]  Victor W. Pike,et al.  Remotely-controlled production of the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635, via 11C-carboxylation of an immobilized Grignard reagent , 1996 .

[76]  W. Wadsak,et al.  Preparation and first evaluation of [(18)F]FE@SUPPY: a new PET tracer for the adenosine A(3) receptor. , 2008, Nuclear medicine and biology.

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

[78]  D. Rubinow,et al.  Estrogen–serotonin interactions: implications for affective regulation , 1998, Biological Psychiatry.

[79]  A. C. Linthorst,et al.  Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. , 2005, Handbook of experimental pharmacology.

[80]  A. Young,et al.  Corticosteroid-serotonin interactions in depression: a review of the human evidence , 2004, Psychopharmacology.

[81]  A. Young,et al.  PET measurement of the influence of corticosteroids on serotonin-1A receptor number , 2001, Biological Psychiatry.

[82]  Claus Lamm,et al.  Time-resolved analysis of fMRI signal changes using Brain Activation Movies , 2008, Journal of Neuroscience Methods.

[83]  Steven Laureys,et al.  Cytology and functionally correlated circuits of human posterior cingulate areas , 2006, NeuroImage.

[84]  Dieter J. Vonderschmitt,et al.  Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS , 2004, Clinical chemistry and laboratory medicine.

[85]  Rupert Lanzenberger,et al.  Model-free fMRI group analysis using FENICA , 2011, NeuroImage.

[86]  Rupert Lanzenberger,et al.  Influence of fMRI smoothing procedures on replicability of fine scale motor localization , 2005, NeuroImage.

[87]  Alan A. Wilson,et al.  Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. , 2002, Archives of general psychiatry.

[88]  Bruce S. McEwen,et al.  INDUCTION OF CORTICOTROPIN-RELEASING HORMONE GENE EXPRESSION BY GLUCOCORTICOIDS: IMPLICATION FOR UNDERSTANDING THE STATES OF FEAR AND ANXIETY AND ALLOSTATIC LOAD , 1998, Psychoneuroendocrinology.

[89]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[90]  C. Sánchez,et al.  [Escitalopram: a selective inhibitor and allosteric modulator of the serotonin transporter]. , 2007, L'Encephale.

[91]  H. Akil,et al.  Serotonin transporter mRNA in rat brain is regulated by classical antidepressants , 1994, Biological Psychiatry.

[92]  M. Héry,et al.  Central 5-HT1 and 5-HT2 binding sites in transgenic mice with reduced glucocorticoid receptor number , 2000, Brain Research.

[93]  J. Cidlowski,et al.  Mechanisms of Glucocorticoid-receptor-mediated Repression of Gene Expression , 1999, Trends in Endocrinology & Metabolism.

[94]  C Windischberger,et al.  Quantification of fMRI artifact reduction by a novel plaster cast head holder , 2000, Human brain mapping.

[95]  Rupert Lanzenberger,et al.  Magnetoencephalography indicates finger motor somatotopy , 2004, The European journal of neuroscience.

[96]  J. Katzenellenbogen,et al.  Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors , 2003, Steroids.

[97]  S. E. Gartside,et al.  Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity , 2004, Journal of psychopharmacology.

[98]  K. Lesch,et al.  Sex hormone‐dependent desensitization of 5‐HT1A autoreceptors in knockout mice deficient in the 5‐HT transporter , 2003, The European journal of neuroscience.

[99]  Hans-Jürgen Möller,et al.  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision , 2002, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[100]  J. Thakore,et al.  HPA axis response to a psychological stressor in generalised social phobia , 2002, Psychoneuroendocrinology.

[101]  C. Sanchez,et al.  L’escitalopram : un inhibiteur sélectif et un modulateur allostérique du transporteur de la sérotonine , 2007 .

[102]  P. Cowen,et al.  Lack of effect of a single dose of hydrocortisone on serotonin1A receptors in recovered depressed patients measured by positron emission tomography with [11C]WAY-100635 , 2003, Biological Psychiatry.

[103]  J. Seckl,et al.  The effect of adrenalectomy on 5-hydroxytryptamine and corticosteroid receptor subtype messenger RNA expression in rat hippocampus , 1995, Neuroscience.

[104]  Peter Herscovitch,et al.  Reduced Serotonin Type 1A Receptor Binding in Panic Disorder , 2004, The Journal of Neuroscience.

[105]  Philip Spinhoven,et al.  Hypothalamus–Pituitary–Adrenal Axis Hyperresponsiveness Is Associated with Increased Social Avoidance Behavior in Social Phobia , 2009, Biological Psychiatry.

[106]  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.

[107]  Rupert Lanzenberger,et al.  The suppressive influence of SMA on M1 in motor imagery revealed by fMRI and dynamic causal modeling , 2008, NeuroImage.

[108]  O. Cameron,et al.  Effect of comorbid anxiety disorders on the Hypothalamic-Pituitary-Adrenal axis response to a social stressor in major depression , 2004, Biological Psychiatry.

[109]  P. Svenningsson,et al.  The role of 5-HT1A receptors in learning and memory , 2008, Behavioural Brain Research.

[110]  M. Millan,et al.  The neurobiology and control of anxious states , 2003, Progress in Neurobiology.

[111]  O. Thews,et al.  Nuclear Medicine and Biology , 2012 .

[112]  E. Akimova,et al.  Auf einen Blick: Multimodale Bildgebung bei einer organischen depressiven Störung mittels fMRT und PET , 2012 .

[113]  W. Wadsak,et al.  Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP. , 2007, Nuclear medicine and biology.

[114]  S. Korte.  Corticosteroids in relation to fear, anxiety and psychopathology , 2001, Neuroscience & Biobehavioral Reviews.

[115]  René Hen,et al.  Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult , 2002, Nature.

[116]  Jian Wang,et al.  Steroid receptor heterodimerization demonstrated in vitro and in vivo. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[117]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[118]  Rupert Lanzenberger,et al.  Central serotonin 1A receptor binding in temporal lobe epilepsy: A [carbonyl-11 C]WAY-100635 PET study , 2010, Epilepsy & Behavior.

[119]  Wolfgang Wadsak,et al.  Reduced Serotonin-1A Receptor Binding in Social Anxiety Disorder , 2007, Biological Psychiatry.

[120]  S. Kasper,et al.  Maintenance pharmacotherapy in schizophrenia , 2009 .

[121]  M. Joëls,et al.  Brain corticosteroid receptor balance in health and disease. , 1998, Endocrine reviews.

[122]  Kjell Någren,et al.  Measurement of Serotonin 5-HT1A Receptor Binding Using Positron Emission Tomography and [carbonyl-11C]WAY-100635—Considerations on the Validity of Cerebellum as a Reference Region , 2007 .

[123]  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.

[124]  William F. Richter,et al.  Modulation of transcriptional sensitivity of mineralocorticoid and estrogen receptors , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[125]  Dennis J. L. G. Schutter,et al.  Testosterone Reduces Unconscious Fear but Not Consciously Experienced Anxiety: Implications for the Disorders of Fear and Anxiety , 2005, Biological Psychiatry.

[126]  Dan J Stein,et al.  Escitalopram in the treatment of social anxiety disorder , 2005, British Journal of Psychiatry.

[127]  L. Nics,et al.  Automatisation and First Evaluation of [18F]FE@SUPPY:2, an AlternativePET-Tracer for the Adenosine A3 Receptor: A Comparison with[18F]FE@SUPPY , 2009 .

[128]  D. Nutt,et al.  Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. , 2008, The British journal of psychiatry : the journal of mental science.

[129]  Rupert Lanzenberger,et al.  Serotonin and molecular neuroimaging in humans using PET , 2011, Amino Acids.

[130]  W. Liu,et al.  in vitro及びin vivoで示されるステロイド受容体ヘテロ二量化 , 1995 .

[131]  O. Meijer,et al.  Coregulator Proteins and Corticosteroid Action in the Brain , 2002, Journal of neuroendocrinology.

[132]  J. Lorberbaum,et al.  Neural correlates of speech anticipatory anxiety in generalized social phobia , 2004, Neuroreport.

[133]  F. Holsboer,et al.  Mice overexpressing CRH show reduced responsiveness in plasma corticosterone after a 5‐HT1A receptor challenge , 2002, Genes, brain, and behavior.

[134]  D. Filipini,et al.  Possible use of glucocorticoid receptor antagonists in the treatment of major depression: preliminary results using RU 486. , 1993, Journal of psychiatry & neuroscience : JPN.

[135]  P A Sargent,et al.  Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635 , 2004, Molecular Psychiatry.

[136]  H. Wikström,et al.  Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]WAY-100635 , 1997, Brain Research.

[137]  Leonardo Bonilha,et al.  NETWORK ATROPHY IN TEMPORAL LOBE EPILEPSY: A VOXEL-BASED MORPHOMETRY STUDY , 2009, Neurology.

[138]  A. Convit,et al.  Cortisol levels during human aging predict hippocampal atrophy and memory deficits , 1998, Nature Neuroscience.

[139]  G. Winocur,et al.  Remembering our past: functional neuroanatomy of recollection of recent and very remote personal events. , 2004, Cerebral cortex.

[140]  Rupert Lanzenberger,et al.  Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study , 2007, Psychopharmacology.

[141]  X. Hu,et al.  The ligand-dependent interaction of mineralocorticoid receptor with coactivator and corepressor peptides suggests multiple activation mechanisms. , 2005, Molecular endocrinology.

[142]  J. Neumaier,et al.  Corticosteroids regulate 5-HT(1A) but not 5-HT(1B) receptor mRNA in rat hippocampus. , 2000, Brain research. Molecular brain research.

[143]  F. Holsboer,et al.  Stress responsive neurohormones in depression and anxiety. , 2003, Pharmacopsychiatry.

[144]  F. Holsboer,et al.  Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. , 1993, European journal of pharmacology.

[145]  N C Andreasen,et al.  Automatic atlas-based volume estimation of human brain regions from MR images. , 1996, Journal of computer assisted tomography.

[146]  C Burger,et al.  A JAVA environment for medical image data analysis: initial application for brain PET quantitation. , 1998, Medical informatics = Medecine et informatique.

[147]  D. Niederwieser,et al.  Double high-dose chemotherapy with autologous peripheral stem cell rescue in relapsed Wilms’ tumor , 1997, Bone Marrow Transplantation.

[148]  Rupert Lanzenberger,et al.  Dissociation of supplementary motor area and primary motor cortex in human subjects when comparing index and little finger movements with functional magnetic resonance imaging , 2001, Neuroscience Letters.

[149]  Rupert Lanzenberger,et al.  Progesterone Level Predicts Serotonin-1A Receptor Binding in the Male Human Brain , 2011, Neuroendocrinology.

[150]  W. Wadsak,et al.  Microfluidic preparation of [18F]FE@SUPPY and [18F]FE@SUPPY:2--comparison with conventional radiosyntheses. , 2011, Nuclear medicine and biology.

[151]  Roger N. Gunn,et al.  Tracer Kinetic Modeling of the 5-HT1AReceptor Ligand [carbonyl-11C]WAY-100635 for PET , 1998, NeuroImage.

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

[153]  S. Watson,et al.  Regulation of Serotonin1A, Glucocorticoid, and Mineralocorticoid Receptor in Rat and Human Hippocampus: Implications for the Neurobiology of Depression , 1998, Biological Psychiatry.

[154]  F. Holsboer,et al.  Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression , 2005, Biological Psychiatry.

[155]  Rhian F. Walther,et al.  Glucocorticoid Receptor Homodimers and Glucocorticoid-Mineralocorticoid Receptor Heterodimers Form in the Cytoplasm through Alternative Dimerization Interfaces , 2001, Molecular and Cellular Biology.

[156]  R. Lanzenberger,et al.  In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram , 2006, Psychopharmacology.

[157]  F. Fazio,et al.  Automation of [11C]acyl chloride syntheses using commercially available 11C-modules. , 2002, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[158]  Y Yonekura,et al.  An introduction to PET and SPECT neuroreceptor quantification models. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[159]  P. Cowen,et al.  Preferential 5-HT1A Autoreceptor Occupancy by Pindolol is Attenuated in Depressed Patients: Effect of Treatment or an Endophenotype of Depression? , 2004, Neuropsychopharmacology.

[160]  J. Streicher,et al.  Diverse Actions of Ovarian Steroids in the Serotonin Neural System , 2002, Frontiers in Neuroendocrinology.

[161]  Rupert Lanzenberger,et al.  Aggression is related to frontal serotonin‐1A receptor distribution as revealed by PET in healthy subjects , 2009, Human brain mapping.

[162]  Dan J Stein,et al.  Endocrine, cognitive and hippocampal/cortical 5HT1A/2A receptor changes evoked by a time-dependent sensitisation (TDS) stress model in rats , 2003, Brain Research.

[163]  Ivo Podreka,et al.  Receptor and Transporter Imaging Studies in Schizophrenia, Depression, Bulimia and Tourette's Disorder—Implications for Psychopharmacology- , 2002, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[164]  H. Akil,et al.  Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.