Positron Emission Tomography Molecular Imaging in Late-Life Depression

Molecular imaging represents a bridge between basic and clinical neuroscience observations and provides many opportunities for translation and identifying mechanisms that may inform prevention and intervention strategies in late-life depression (LLD). Substantial advances in instrumentation and radiotracer chemistry have resulted in improved sensitivity and spatial resolution and the ability to study in vivo an increasing number of neurotransmitters, neuromodulators, and, importantly, neuropathological processes. Molecular brain imaging studies in LLD will be reviewed, with a primary focus on positron emission tomography. Future directions for the field of molecular imaging in LLD will be discussed, including integrating molecular imaging with genetic, neuropsychiatric, and cognitive outcomes and multimodality neuroimaging.

[1]  Min-Ying Su,et al.  Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. , 2013, Journal of Alzheimer's disease : JAD.

[2]  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.

[3]  Alastair Flint,et al.  Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[4]  Gregor Hasler,et al.  Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. , 2007, Archives of general psychiatry.

[5]  Dean F Wong,et al.  The Role of Imaging in Proof of Concept for CNS Drug Discovery and Development , 2009, Neuropsychopharmacology.

[6]  Bradford D Henderson,et al.  Highlighting the Versatility of the Tracerlab Synthesis Modules. Part 1: Fully Automated Production of [F]Labelled Radiopharmaceuticals using a Tracerlab FX(FN). , 2011, Journal of labelled compounds & radiopharmaceuticals.

[7]  Wolfgang Gaebel,et al.  Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT , 1999, Psychiatry Research: Neuroimaging.

[8]  H. Sackeim,et al.  Effects of antidepressant medication on rCBF in late-life depression , 1994, Biological Psychiatry.

[9]  Masanori Ichise,et al.  Serotonin Transporter Binding in Bipolar Disorder Assessed using [11C]DASB and Positron Emission Tomography , 2006, Biological Psychiatry.

[10]  D. Kupfer,et al.  Measurement of 5‐HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY‐100635 , 2007, Synapse.

[11]  C. de Montigny,et al.  Modification of serotonergic and noradrenergic neurotransmissions by repeated administration of monoamine oxidase inhibitors: electrophysiological studies in the rat central nervous system. , 1986, The Journal of pharmacology and experimental therapeutics.

[12]  W. Drevets,et al.  Dopamine Type-1 Receptor Binding in Major Depressive Disorder Assessed using Positron Emission Tomography and [11C]NNC-112 , 2008, Neuropsychopharmacology.

[13]  J. Schildkraut,et al.  The catecholamine hypothesis of affective disorders. A review of supporting evidence. , 1967, International journal of psychiatry.

[14]  J. Mazziotta,et al.  Positron emission tomography and autoradiography: Principles and applications for the brain and heart , 1985 .

[15]  Gwenn S. Smith,et al.  Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[16]  G. Oxenkrug,et al.  Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. , 1969, Lancet.

[17]  M N Smolka,et al.  Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study , 2008, Molecular Psychiatry.

[18]  Jonathan M. Links,et al.  Imaging dopamine receptors in the human brain by positron tomography , 1983 .

[19]  M. Mintun,et al.  Decreased Hippocampal 5-HT2A Receptor Binding in Older Depressed Patients Using [18F]Altanserin Positron Emission Tomography , 2004, Neuropsychopharmacology.

[20]  Robert Barber,et al.  Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study. , 2002, Archives of general psychiatry.

[21]  H. Lavretsky,et al.  Methylphenidate augmentation of citalopram in elderly depressed patients. , 2001, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[22]  Andrea Ciarmiello,et al.  PET translates neurophysiology into images: A review to stimulate a network between neuroimaging and basic research , 2011, Journal of cellular physiology.

[23]  Iwao Kanno,et al.  Functional and structural synergy for resolution recovery and partial volume correction in brain PET , 2009, NeuroImage.

[24]  R. Parsey,et al.  Dopamine D2 receptor availability and amphetamine-induced dopamine release in unipolar depression , 2001, Biological Psychiatry.

[25]  Kris Thielemans,et al.  Correction of head movement on PET studies: comparison of methods. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  S. Gershon,et al.  Dopamine and depression , 2005, Journal of Neural Transmission / General Section JNT.

[27]  A. Laird,et al.  A meta‐analytic study of changes in brain activation in depression , 2008 .

[28]  R. Carson,et al.  PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S,S)‐[11C]O‐methylreboxetine and HRRT , 2010, Synapse.

[29]  C. Zarate,et al.  Ketamine and the next generation of antidepressants with a rapid onset of action. , 2009, Pharmacology & therapeutics.

[30]  Sylvain Houle,et al.  Lower dopamine transporter binding potential in striatum during depression , 2001, Neuroreport.

[31]  I. Ferrier,et al.  A study of the serotonin transporter in the prefrontal cortex in late‐life depression and Alzheimer's disease with and without depression , 2006, Neuropathology and applied neurobiology.

[32]  Faith M. Gunning-Dixon,et al.  Translational Research in Late-Life Mood Disorders: Implications for Future Intervention and Prevention Research , 2007, Neuropsychopharmacology.

[33]  Dean F. Wong,et al.  Accurate Event-Driven Motion Compensation in High-Resolution PET Incorporating Scattered and Random Events , 2008, IEEE Transactions on Medical Imaging.

[34]  J. Seibyl,et al.  Brain SPECT imaging of amphetamine-induced dopamine release in euthymic bipolar disorder patients. , 2000, The American journal of psychiatry.

[35]  W. Klunk,et al.  Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. , 2003, Journal of medicinal chemistry.

[36]  M. Furey,et al.  Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. , 2006, Archives of general psychiatry.

[37]  C. Katona,et al.  Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls , 1997, Brain Research.

[38]  H. Mayberg Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. , 2003, British medical bulletin.

[39]  Pedro Rosa-Neto,et al.  Measurement of brain regional alpha-[11C]methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression. , 2004, Archives of general psychiatry.

[40]  Alan J. Thomas,et al.  The immunhistochemical examination of GABAergic interneuron markers in the dorsolateral prefrontal cortex of patients with late-life depression , 2010, International Psychogeriatrics.

[41]  N. Volkow,et al.  Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. , 1998, The American journal of psychiatry.

[42]  Alan A. Wilson,et al.  Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. , 2001, The American journal of psychiatry.

[43]  Gwenn S. Smith,et al.  The functional neuroanatomy of geriatric depression , 2009, International journal of geriatric psychiatry.

[44]  Ramin V. Parsey,et al.  Acute Occupancy of Brain Serotonin Transporter by Sertraline as Measured by [11C]DASB and Positron Emission Tomography , 2006, Biological Psychiatry.

[45]  E. Corruble,et al.  Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors , 1997, Psychopharmacology.

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

[47]  Gwenn S. Smith,et al.  The relationship between the acute cerebral metabolic response to citalopram and chronic citalopram treatment outcome. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[48]  Masanori Ichise,et al.  Elevated Serotonin Transporter Binding in Major Depressive Disorder Assessed Using Positron Emission Tomography and [11C]DASB; Comparison with Bipolar Disorder , 2007, Biological Psychiatry.

[49]  Alan J. Thomas,et al.  Cellular morphometry in late-life depression: a review of postmortem studies. , 2014, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[50]  H. Ågren,et al.  PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. , 1994, Pharmacopsychiatry.

[51]  A. Carlsson,et al.  The Monoamine Stabilizer (-)-OSU6162 Attenuates Voluntary Ethanol Intake and Ethanol-Induced Dopamine Output in Nucleus Accumbens , 2012, Biological Psychiatry.

[52]  J R Moeller,et al.  Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression. , 2000, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[53]  R. Blakely,et al.  The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters , 2006, Neuropsychopharmacology.

[54]  Alan J. Thomas,et al.  Neuropathological correlates of late-life depression in older people , 2011, British Journal of Psychiatry.

[55]  R. Robinson,et al.  Treatment of vascular depression using repetitive transcranial magnetic stimulation. , 2008, Archives of general psychiatry.

[56]  E. Perry,et al.  5-HT receptor binding in post-mortem brain from patients with affective disorder. , 1987, Journal of affective disorders.

[57]  B. Mulsant,et al.  PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. , 1999, The American journal of psychiatry.

[58]  G. Small,et al.  Protein binding in patients with late-life depression. , 2011, Archives of general psychiatry.

[59]  H. Manji,et al.  Novel Drugs and Therapeutic Targets for Severe Mood Disorders , 2008, Neuropsychopharmacology.

[60]  H. Fukuda,et al.  D1 dopamine receptor binding in mood disorders measured by positron emission tomography , 2005, Psychopharmacology.

[61]  Anne W. Schmidt,et al.  Identification of multiple 5-HT₄ partial agonist clinical candidates for the treatment of Alzheimer's disease. , 2012, Journal of medicinal chemistry.

[62]  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.

[63]  Garth L. Maker,et al.  A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers , 2014, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[64]  D. Kupfer,et al.  Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression. , 1999, The American journal of psychiatry.

[65]  Angela R Laird,et al.  A meta‐analytic study of changes in brain activation in depression , 2008, Human brain mapping.

[66]  P. Liddle,et al.  Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone. , 1999, Archives of general psychiatry.

[67]  B. Reisberg,et al.  Positron Emission Tomography in the Study of Aging and Senile Dementia , 1980, Neurobiology of Aging.

[68]  G. Muehllehner,et al.  Positron emission tomography , 2006, Physics in medicine and biology.

[69]  T. Higuchi,et al.  Regional cerebral blood flow in mood disorders , 1997 .

[70]  J. M. Ollinger,et al.  Positron Emission Tomography , 2018, Handbook of Small Animal Imaging.

[71]  J. Krystal,et al.  GABA and glutamate systems as therapeutic targets in depression and mood disorders , 2005, Expert opinion on therapeutic targets.

[72]  Steen Jakobsen,et al.  Radiosynthesis and Characterization of 11C-GSK215083 as a PET Radioligand for the 5-HT6 Receptor , 2012, The Journal of Nuclear Medicine.

[73]  S. Kapur,et al.  Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study. , 1999, The American journal of psychiatry.

[74]  Gwenn S. Smith,et al.  Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression: A randomized, placebo-controlled study , 2009, Psychiatry Research: Neuroimaging.

[75]  J. Mazziotta,et al.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. , 1987, Archives of general psychiatry.

[76]  K. Denicoff,et al.  Regulation of Cellular Plasticity Cascades in the Pathophysiology and Treatment of Mood Disorders , 2003, Annals of the New York Academy of Sciences.

[77]  A. Kumar,et al.  Functional brain imaging in late-life depression and dementia. , 1993, The Journal of clinical psychiatry.

[78]  D. Townsend Multimodality imaging of structure and function , 2008, Physics in medicine and biology.

[79]  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.

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

[81]  J John Mann,et al.  Role of the Serotonergic System in the Pathogenesis of Major Depression and Suicidal Behavior , 1999, Neuropsychopharmacology.

[82]  M S Buchsbaum,et al.  Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia. , 1982, Archives of general psychiatry.

[83]  Gregor Hasler,et al.  Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. , 2011, The American journal of psychiatry.

[84]  Robert B. Innis,et al.  Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors , 2004, Biological Psychiatry.

[85]  Charles L. Raison,et al.  Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression , 2009, Biological Psychiatry.

[86]  D. Murphy,et al.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. , 1990, Archives of general psychiatry.

[87]  David Eidelberg,et al.  Distinct functional networks associated with improvement of affective symptoms and cognitive function during citalopram treatment in geriatric depression , 2011, Human brain mapping.

[88]  A. Alavi,et al.  Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[89]  C. D. Arnett,et al.  Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[90]  Alexander Hammers,et al.  Functional and structural synergy for resolution recovery and partial volume correction in brain PET , 2009, NeuroImage.

[91]  V. Arango,et al.  Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. , 1990, Archives of general psychiatry.

[92]  T. van Amelsvoort,et al.  Imaging as tool to investigate psychoses and antipsychotics. , 2012, Handbook of experimental pharmacology.

[93]  Alan A. Wilson,et al.  The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study. , 2001, The American journal of psychiatry.

[94]  Sylvain Houle,et al.  Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. , 2004, Archives of general psychiatry.

[95]  Zubin Bhagwagar,et al.  Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [(11)C]MDL 100,907. , 2006, The American journal of psychiatry.

[96]  G. Small,et al.  Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults. , 2009, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[97]  David Eidelberg,et al.  Serotonin Modulation of Cerebral Glucose Metabolism in Depressed Older Adults , 2009, Biological Psychiatry.

[98]  Hervé Boutin,et al.  Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[99]  Arman Rahmim,et al.  Design and Implementation of an Automated Partial Volume Correction in PET: Application to Dopamine Receptor Quantification in the Normal Human Striatum , 2008, Journal of Nuclear Medicine.

[100]  Claus Svarer,et al.  Kinetic Modeling of 11C-SB207145 Binding to 5-HT4 Receptors in the Human Brain In Vivo , 2009, Journal of Nuclear Medicine.

[101]  E. Nestler,et al.  The Mesolimbic Dopamine Reward Circuit in Depression , 2006, Biological Psychiatry.

[102]  W. K. Cullen,et al.  Alzheimer’s Disease Amyloid β-Protein and Synaptic Function , 2010, NeuroMolecular Medicine.

[103]  F. Fazio,et al.  Effects of Fluvoxamine Treatment on the in Vivo Binding of [F-18]FESP in Drug Naive Depressed Patients: A Pet Study , 2000, NeuroImage.

[104]  J. Mazziotta,et al.  Positron emission tomographic study of affective disorders: Problems and strategies , 1984, Annals of neurology.

[105]  Juha Markkula,et al.  Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET , 2008, Psychopharmacology.

[106]  P. Cowen,et al.  5-HTT binding in recovered depressed patients and healthy volunteers: a positron emission tomography study with [11C]DASB. , 2007, The American journal of psychiatry.

[107]  Wayne C. Drevets,et al.  Neuroreceptor imaging in depression , 2013, Neurobiology of Disease.

[108]  R. Carson,et al.  The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study , 2013, Brain, Behavior, and Immunity.

[109]  V. Klimek,et al.  Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study , 2002, Biological Psychiatry.

[110]  Klaus Wienhard,et al.  Measurement of glucose consumption using [(18)F]fluorodeoxyglucose. , 2002, Methods.

[111]  C. Nemeroff,et al.  The serotonin transporter and depression , 1998, Depression and anxiety.

[112]  P. Brambilla,et al.  GABAergic dysfunction in mood disorders , 2003, Molecular Psychiatry.

[113]  Christer Halldin,et al.  [11C]AZ10419369: A selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain , 2008, NeuroImage.

[114]  W. Drevets,et al.  Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder. , 2006, Archives of general psychiatry.

[115]  A. Sauter,et al.  Combined PET/MR Imaging — Technology and Applications , 2010, Technology in cancer research & treatment.

[116]  Sati Mazumdar,et al.  Serotonin 1A Receptor Binding and Treatment Response in Late-Life Depression , 2004, Neuropsychopharmacology.

[117]  J. Mendlewicz,et al.  Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex , 1997, British Journal of Psychiatry.

[118]  R Todd Ogden,et al.  Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder. , 2008, Journal of psychiatric research.

[119]  C. Reynolds,et al.  Imaging Alzheimer Pathology in Late-Life Depression With PET and Pittsburgh Compound-B , 2008, Alzheimer disease and associated disorders.

[120]  B. Pollock,et al.  Neuropathologic Correlates of Late-Onset Major Depression , 2004, Neuropsychopharmacology.

[121]  Benjamin J. Shannon,et al.  Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory , 2005, The Journal of Neuroscience.

[122]  N. Volkow,et al.  Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging , 1998, Annals of neurology.

[123]  Paul J Carlson,et al.  A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. , 2006, Archives of general psychiatry.

[124]  Andrew J Montgomery,et al.  Extrastriatal D2 and striatal D2 receptors in depressive illness: pilot PET studies using [11C]FLB 457 and [11C]raclopride. , 2007, Journal of affective disorders.

[125]  D. Keegan,et al.  Mental dysfunction and the blockade of muscarinic receptors in the brains of the normal elderly , 1985, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[126]  G. Rajkowska,et al.  Increase in Serotonin-1A Autoreceptors in the Midbrain of Suicide Victims with Major Depression—Postmortem Evidence for Decreased Serotonin Activity , 1998, The Journal of Neuroscience.

[127]  W. Klunk,et al.  Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease , 2013, Molecular Imaging and Biology.

[128]  B. Långström,et al.  Low brain uptake of L‐[11C]5‐hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers , 1991, Acta psychiatrica Scandinavica.

[129]  Alan A. Wilson,et al.  Elevated putamen D(2) receptor binding potential in major depression with motor retardation: an [11C]raclopride positron emission tomography study. , 2006, The American journal of psychiatry.

[130]  Anna Barnes,et al.  Acute and chronic effects of citalopram on cerebral glucose metabolism in geriatric depression. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[131]  Min-Ying Su,et al.  Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. , 2014, Journal of Alzheimer's disease : JAD.

[132]  J. Links,et al.  Imaging dopamine receptors in the human brain by positron tomography. , 1984, Science.

[133]  M. Furey,et al.  Antidepressant Effects of the Muscarinic Cholinergic Receptor Antagonist Scopolamine: A Review , 2013, Biological Psychiatry.