Imaging treatment effects in depression

Abstract In the past years a multitude of studies has revealed alterations on a neuromolecular, structural and network level in patients with major depressive disorder within key regions of emotion and cognition processing as well as implicated neurotransmitter systems. The present review is thought to give an overview over recent developments with regard to treatment-induced changes in structural, functional and molecular neuroimaging. A number of studies could show that antidepressant treatment may lead to a partial restorage of primarily altered processes. This becomes evident in structural magnetic resonance imaging studies which point towards the reduction of volumetric differences between depressed patients and healthy controls during treatment, along with a normalization of neuronal functioning as assessed with functional magnetic resonance imaging. On a molecular level positron emission tomography studies investigating targets which are fundamentally implicated in antidepressant action such as serotonergic and dopaminergic transporters and receptors have shown to be sustainably influenced by antidepressant treatment. However, it seems that not all dysfunctional processes can be reversed by antidepressant treatment and that state and trait factors are evident not only on a behavioral but also on a neurobiological level.

[1]  Kristin Clark,et al.  Enhanced Long-Term Synaptic Depression in an Animal Model of Depression , 2007, Biological Psychiatry.

[2]  E. Smeraldi,et al.  Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine , 1998, Molecular Psychiatry.

[3]  Joseph E LeDoux Emotion Circuits in the Brain , 2000 .

[4]  L. Lanfumey,et al.  Early desensitization of somato-dendritic 5-HT1A autoreceptors in rats treated with fluoxetine or paroxetine , 1995, Naunyn-Schmiedeberg's Archives of Pharmacology.

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

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

[7]  H. Praag No functional psychopharmacology without functional psychopathology , 2010 .

[8]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[9]  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.

[10]  D. Pizzagalli Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response , 2011, Neuropsychopharmacology.

[11]  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.

[12]  H. Barbas,et al.  Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression , 2003, BMC Neuroscience.

[13]  K. Luan Phan,et al.  Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging , 2003, NeuroImage.

[14]  P. Cowen,et al.  Increased neural response to fear in patients recovered from depression: a 3T functional magnetic resonance imaging study , 2009, Psychological Medicine.

[15]  B Beuthien-Baumann,et al.  Changes in brain metabolism associated with remission in unipolar major depression , 2004, Acta psychiatrica Scandinavica.

[16]  N. Kalin,et al.  Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation , 2009, Proceedings of the National Academy of Sciences.

[17]  J. Groves,et al.  Is it time to reassess the BDNF hypothesis of depression? , 2007, Molecular Psychiatry.

[18]  R. Parsey,et al.  Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment , 2009, Psychiatry Research: Neuroimaging.

[19]  R. Blakely,et al.  Biogenic amine transporters: regulation in flux , 2000, Current Opinion in Neurobiology.

[20]  J. Ballenger Analysis of Association Between the Serotonin Transporter and Antidepressant Response in a Large Clinical Sample , 2008 .

[21]  I. Moilanen,et al.  Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents , 2000, Molecular Psychiatry.

[22]  Jeffrey M. Zacks,et al.  Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses , 2006, Nature Neuroscience.

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

[24]  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.

[25]  Johan Gabrielsson,et al.  Mechanistic model of acute autoinhibitory feedback action after administration of SSRIs in rats: application to escitalopram-induced effects on brain serotonin levels. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[26]  Steven C. R. Williams,et al.  The Neural Correlates of Anhedonia in Major Depressive Disorder , 2005, Biological Psychiatry.

[27]  H. Möller,et al.  Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression , 2008, Molecular Psychiatry.

[28]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

[29]  Ellen Frank,et al.  Anatomical MRI Study of Subgenual Prefrontal Cortex in Bipolar and Unipolar Subjects , 2002, Neuropsychopharmacology.

[30]  M. Yücel,et al.  Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. , 2009, Journal of affective disorders.

[31]  David Goldman,et al.  Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. , 2006, American journal of human genetics.

[32]  C. Antke,et al.  In vivo imaging of synaptic function in the central nervous system: II. Mental and affective disorders , 2009, Behavioural Brain Research.

[33]  Rupert Lanzenberger,et al.  Author ' s personal copy Area-speci fi c modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI : A randomized cross-over study , 2009 .

[34]  Samuel M. McClure,et al.  Temporal Prediction Errors in a Passive Learning Task Activate Human Striatum , 2003, Neuron.

[35]  R. Hen,et al.  Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants , 2003, Science.

[36]  Victoria Arango,et al.  Volumetric Analysis of the Prefrontal Cortex, Amygdala, and Hippocampus in Major Depression , 2004, Neuropsychopharmacology.

[37]  J. Hietanen,et al.  Depression biases the recognition of emotionally neutral faces , 2004, Psychiatry Research.

[38]  E. Gordon,et al.  Improving the Prediction of Treatment Response in Depression: Integration of Clinical, Cognitive, Psychophysiological, Neuroimaging, and Genetic Measures , 2008, CNS Spectrums.

[39]  Dennis S. Charney,et al.  Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects , 2005, Biological Psychiatry.

[40]  K. Luan Phan,et al.  Functional Neuroanatomy of Emotion: A Meta-Analysis of Emotion Activation Studies in PET and fMRI , 2002, NeuroImage.

[41]  Laurent Descarries,et al.  Toward brain imaging of serotonin 5-HT1A autoreceptor internalization , 2004, NeuroImage.

[42]  P. Cowen,et al.  Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. , 2004, The American journal of psychiatry.

[43]  R. Post,et al.  Venlafaxine or bupropion responders but not nonresponders show baseline prefrontal and paralimbic hypometabolism compared with controls. , 1996, Psychopharmacology bulletin.

[44]  J. Haxby,et al.  Human neural systems for face recognition and social communication , 2002, Biological Psychiatry.

[45]  P. Blier,et al.  Autoregulation of serotonin neurons: role in antidepressant drug action. , 1999, Pharmacological reviews.

[46]  R. Elliott,et al.  Assessing human 5-HT function in vivo with pharmacoMRI , 2008, Neuropharmacology.

[47]  A. Serretti,et al.  Pharmacogenetics of antidepressant response. , 2011, Journal of psychiatry & neuroscience : JPN.

[48]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[49]  J. Mazziotta,et al.  Reduction of prefrontal cortex glucose metabolism common to three types of depression. , 1989, Archives of general psychiatry.

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

[51]  M S Buchsbaum,et al.  Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. , 1999, The American journal of psychiatry.

[52]  Yang Wang,et al.  Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. , 2007, The Journal of neuropsychiatry and clinical neurosciences.

[53]  Victoria Arango,et al.  Serotonin 1A Receptors, Serotonin Transporter Binding and Serotonin Transporter mRNA Expression in the Brainstem of Depressed Suicide Victims , 2001, Neuropsychopharmacology.

[54]  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.

[55]  Joost Janssen,et al.  Cerebral volume measurements and subcortical white matter lesions and short‐term treatment response in late life depression , 2007, International journal of geriatric psychiatry.

[56]  Ö. Kapucu,et al.  Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method , 2004, European Journal of Nuclear Medicine.

[57]  S. Haber The primate basal ganglia: parallel and integrative networks , 2003, Journal of Chemical Neuroanatomy.

[58]  R. Vanninen,et al.  Changes in midbrain serotonin transporter availability in atypically depressed subjects after oneyear of psychotherapy , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[59]  H. Rollema,et al.  Activation of postsynaptic 5‐HT1A receptors by fluoxetine despite the loss of firing‐dependent serotonergic input: Electrophysiological and neurochemical studies , 2001, Synapse.

[60]  J. Amsterdam,et al.  PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression. , 2004, Journal of affective disorders.

[61]  A. Tanács,et al.  Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study. , 2005, Journal of affective disorders.

[62]  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.

[63]  M. Lowe,et al.  Activity and Connectivity of Brain Mood Regulating Circuit in Depression: A Functional Magnetic Resonance Study , 2005, Biological Psychiatry.

[64]  Klaus P. Ebmeier,et al.  Clinical and psychometric correlates of dopamine D2 binding in depression , 1997, Psychological Medicine.

[65]  S. Houle,et al.  Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. , 2001, The American journal of psychiatry.

[66]  M. Mintun,et al.  ltered Emotional Interference Processing in Affective nd Cognitive-Control Brain Circuitry in Major epression hristina , 2008 .

[67]  Nicholas D. Walsh,et al.  Functional Coupling of the Amygdala in Depressed Patients Treated with Antidepressant Medication , 2008, Neuropsychopharmacology.

[68]  Klaus P. Ebmeier,et al.  Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression , 1998, British Journal of Psychiatry.

[69]  Eric Vermetten,et al.  Reduced volume of orbitofrontal cortex in major depression , 2002, Biological Psychiatry.

[70]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[71]  D. Steffens,et al.  Hippocampal volume and antidepressant response in geriatric depression , 2002, International journal of geriatric psychiatry.

[72]  E. Castrén,et al.  Is mood chemistry? , 2005, Nature Reviews Neuroscience.

[73]  Erno J. Hermans,et al.  Two-Week Administration of the Combined Serotonin-Noradrenaline Reuptake Inhibitor Duloxetine Augments Functioning of Mesolimbic Incentive Processing Circuits , 2011, Biological Psychiatry.

[74]  Beatriz Rico,et al.  The Primate Thalamus Is a Key Target for Brain Dopamine , 2005, The Journal of Neuroscience.

[75]  Deborah A Yurgelun-Todd,et al.  Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study , 2000, Biological Psychiatry.

[76]  A. Meyer-Lindenberg,et al.  Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression , 2008, Molecular Psychiatry.

[77]  Heinrich Sauer,et al.  Differential effects of serotonergic and noradrenergic antidepressants on brain activity during a cognitive control task and neurofunctional prediction of treatment outcome in patients with depression. , 2010, Journal of psychiatry & neuroscience : JPN.

[78]  P. Jerabek,et al.  Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response , 2000, Biological Psychiatry.

[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]  K. Rasmussen,et al.  Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat , 2000, Naunyn-Schmiedeberg's Archives of Pharmacology.

[81]  E. Bora,et al.  Gray matter abnormalities in Major Depressive Disorder: a meta-analysis of voxel based morphometry studies. , 2012, Journal of affective disorders.

[82]  P. D’Aquila,et al.  The role of dopamine in the mechanism of action of antidepressant drugs. , 2000, European journal of pharmacology.

[83]  D. Murphy,et al.  Serotonergically induced hormonal responses and the antidepressant effect of total sleep deprivation in patients with major depression. , 1988, Psychopharmacology bulletin.

[84]  Jeffrey L. Birk,et al.  Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. , 2009, The American journal of psychiatry.

[85]  Kjell Någren,et al.  Effects of fluoxetine on dopamine D2 receptors in the human brain: a positron emission tomography study with [11C]raclopride. , 2004, The international journal of neuropsychopharmacology.

[86]  Rupert Lanzenberger,et al.  Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram , 2009, International clinical psychopharmacology.

[87]  Alan A. Wilson,et al.  Brain monoamine oxidase A binding in major depressive disorder: relationship to selective serotonin reuptake inhibitor treatment, recovery, and recurrence. , 2009, Archives of general psychiatry.

[88]  A. Young,et al.  A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder , 2005, Biological Psychiatry.

[89]  R. Sapolsky,et al.  The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death , 2000, Biological Psychiatry.

[90]  S. Kasper,et al.  The role of pharmacogenetics in the treatment of depression and anxiety disorders , 2009, International clinical psychopharmacology.

[91]  Ellen Frank,et al.  Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression , 2004, Psychiatry Research: Neuroimaging.

[92]  H. Fibiger,et al.  Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis. , 1989, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

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

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

[95]  Sophie Guionnet,et al.  Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies. , 2011, Journal of affective disorders.

[96]  John Suckling,et al.  Brain Imaging Correlates of Depressive Symptom Severity and Predictors of Symptom Improvement After Antidepressant Treatment , 2007, Biological Psychiatry.

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

[98]  M. Alda,et al.  Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. , 2008, Journal of psychiatry & neuroscience : JPN.

[99]  Michele T. Diaz,et al.  Effect of bupropion extended release on negative emotion processing in major depressive disorder: a pilot functional magnetic resonance imaging study. , 2007, The Journal of clinical psychiatry.

[100]  Alan A. Wilson,et al.  Bupropion occupancy of the dopamine transporter is low during clinical treatment , 2002, Psychopharmacology.

[101]  C. Halldin,et al.  PET measurement of serotonin transporter occupancy: a comparison of escitalopram and citalopram. , 2007, The international journal of neuropsychopharmacology.

[102]  J Tauscher,et al.  [123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. , 2000, Biological psychiatry.

[103]  G. Pourtois,et al.  Distributed and interactive brain mechanisms during emotion face perception: Evidence from functional neuroimaging , 2007, Neuropsychologia.

[104]  V. Arango,et al.  A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. , 2000, Archives of general psychiatry.

[105]  H. Štěpánková,et al.  Cognitive deficits in the euthymic phase of unipolar depression , 2009, Psychiatry Research.

[106]  M. Thase,et al.  Can’t shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals , 2002, Biological Psychiatry.

[107]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[108]  Subrata K. Bose,et al.  Diminished brain 5-HT transporter binding in major depression: a positron emission tomography study with [11C]DASB , 2011, Psychopharmacology.

[109]  Sara M. Levens,et al.  Updating positive and negative stimuli in working memory in depression. , 2010, Journal of experimental psychology. General.

[110]  C. Altar Neurotrophins and depression. , 1999, Trends in pharmacological sciences.

[111]  A. Sorensen,et al.  Spontaneous Low-Frequency BOLD Signal Fluctuations : Changes in Default Mode Network in Brain Diseased with Glioblastoma , 2009 .

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

[113]  G. MacQueen,et al.  Increased temporal cortex CREB concentrations and antidepressant treatment in major depression , 1998, The Lancet.

[114]  J. Amsterdam,et al.  Greater availability of brain dopamine transporters in major depression shown by [99m Tc]TRODAT-1 SPECT imaging. , 2003, The American journal of psychiatry.

[115]  R. Blakely,et al.  Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. , 1999, Science.

[116]  Catherine J. Harmer,et al.  Effect of a single dose of citalopram on amygdala response to emotional faces , 2009, British Journal of Psychiatry.

[117]  D. Kupfer,et al.  Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression , 2000, Neuropsychopharmacology.

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

[119]  H. V. van Praag No functional psychopharmacology without functional psychopathology , 2010, Acta psychiatrica Scandinavica.

[120]  Ciara McCabe,et al.  Antidepressant medications reduce subcortical–cortical resting-state functional connectivity in healthy volunteers , 2011, NeuroImage.

[121]  A. Blamire,et al.  Region‐specific effects of a tyrosine‐free amino acid mixture on amphetamine‐induced changes in BOLD fMRI signal in the rat brain , 2007, Synapse.

[122]  F. Yasuno,et al.  Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652 , 2002, Biological Psychiatry.

[123]  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.

[124]  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.

[125]  B. Feige,et al.  Learning as a Model for Neural Plasticity in Major Depression , 2010, Biological Psychiatry.

[126]  J. Haxby,et al.  Neural systems for recognition of familiar faces , 2007, Neuropsychologia.

[127]  R. Vanninen,et al.  Midbrain binding of [123I]nor-beta-CIT in atypical depression. , 2006, Progress in neuro-psychopharmacology & biological psychiatry.

[128]  J. Mendlewicz,et al.  Time-dependent effects of escitalopram on brain derived neurotrophic factor (BDNF) and neuroplasticity related targets in the central nervous system of rats. , 2010, European journal of pharmacology.

[129]  Biological psychiatry: still marching forward in a dead end , 2010 .

[130]  H. Kraemer,et al.  Untreated depression and hippocampal volume loss. , 2003, The American journal of psychiatry.

[131]  Glen Wiesner,et al.  Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. , 2008, Archives of general psychiatry.

[132]  M. Thase Treatment-resistant depression: prevalence, risk factors, and treatment strategies. , 2011, The Journal of clinical psychiatry.

[133]  Matthew L. Ho,et al.  Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. , 2003, The American journal of psychiatry.

[134]  S. Alborzian,et al.  Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine , 1999, Psychiatry Research: Neuroimaging.

[135]  Henrik Walter,et al.  Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study. , 2008, Journal of affective disorders.

[136]  D. Nutt The role of dopamine and norepinephrine in depression and antidepressant treatment. , 2006, The Journal of clinical psychiatry.

[137]  S. M. Persad,et al.  Differences between depressed and nondepressed individuals in the recognition of and response to facial emotional cues. , 1993, Journal of abnormal psychology.

[138]  Laurent Descarries,et al.  Decreased [18F]MPPF Binding Potential in the Dorsal Raphe Nucleus After a Single Oral Dose of Fluoxetine: A Positron-Emission Tomography Study in Healthy Volunteers , 2008, Biological Psychiatry.

[139]  W. Coryell,et al.  Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. , 1999, The American journal of psychiatry.

[140]  H. Kraemer,et al.  Facial emotion discrimination: II. Behavioral findings in depression , 1992, Psychiatry Research.

[141]  W. Drevets,et al.  Imaging phenotypes of major depressive disorder: genetic correlates , 2009, Neuroscience.

[142]  Mark Lau,et al.  Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. , 2004, Archives of general psychiatry.

[143]  R. V. Van Heertum,et al.  Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [11C]McN 5652 , 2002, Psychopharmacology.

[144]  M. Wiesmann,et al.  Neural correlates of treatment outcome in major depression. , 2011, The international journal of neuropsychopharmacology.

[145]  P. Fox,et al.  Cingulate function in depression: a potential predictor of treatment response , 1997, Neuroreport.

[146]  Vincent A Magnotta,et al.  Hippocampal volume and 2-year outcome in depression. , 2008, The British journal of psychiatry : the journal of mental science.

[147]  Terry L. Jernigan,et al.  Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes , 2010, Biological Psychiatry.

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

[149]  V. Haughton,et al.  Mapping functionally related regions of brain with functional connectivity MR imaging. , 2000, AJNR. American journal of neuroradiology.

[150]  Marc Laruelle,et al.  Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain , 2010, NeuroImage.

[151]  S. Tanada,et al.  A dose-finding study of duloxetine based on serotonin transporter occupancy , 2006, Psychopharmacology.

[152]  John Suckling,et al.  Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. , 2004, Archives of general psychiatry.

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

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

[155]  Patrice Boyer,et al.  Neuroplasticity: from MRI to depressive symptoms , 2004, European Neuropsychopharmacology.

[156]  H. Imhof,et al.  White matter hyperintensities and chronicity of depression. , 2005, Journal of psychiatric research.

[157]  S. Kasper,et al.  Nocturnal TSH and prolactin secretion during sleep deprivation and prediction of antidepressant response in patients with major depression , 1988, Biological Psychiatry.

[158]  J. Seok,et al.  Serotonin Transporter Gene Polymorphism Associated with Short-Term Treatment Response to Venlafaxine , 2010, Neuropsychobiology.

[159]  R. Post,et al.  Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression , 2005, Biological Psychiatry.

[160]  C. Lange,et al.  Enlarged amygdala volume and reduced hippocampal volume in young women with major depression , 2004, Psychological Medicine.

[161]  Michael J. Anderle,et al.  The neural substrates of affective processing in depressed patients treated with venlafaxine. , 2003, The American journal of psychiatry.

[162]  A. Falini,et al.  Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression. , 2011, Journal of affective disorders.

[163]  Eric Vermetten,et al.  Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment , 2004, Biological Psychiatry.

[164]  J. Ashburner,et al.  Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression , 2009, PloS one.

[165]  D J Kupfer,et al.  Serotonin type-1A receptor imaging in depression. , 2000, Nuclear medicine and biology.

[166]  L. Squire,et al.  Neuroanatomy of memory. , 1993, Annual review of neuroscience.

[167]  Florin Dolcos,et al.  Prefrontal mechanisms for executive control over emotional distraction are altered in major depression , 2008, Psychiatry Research: Neuroimaging.

[168]  P. Skudlarski,et al.  Brain Connectivity Is Not Only Lower but Different in Schizophrenia: A Combined Anatomical and Functional Approach , 2010, Biological Psychiatry.

[169]  S. Rauch,et al.  Neurobiology of emotion perception II: implications for major psychiatric disorders , 2003, Biological Psychiatry.

[170]  Rebecca Elliott,et al.  Affective Cognition and its Disruption in Mood Disorders , 2011, Neuropsychopharmacology.

[171]  Martin Wiesmann,et al.  Different effects of mirtazapine and venlafaxine on brain activation: an open randomized controlled fMRI study. , 2011, The Journal of clinical psychiatry.

[172]  C. Nemeroff,et al.  The role of dopamine in the pathophysiology of depression. , 2007, Archives of general psychiatry.

[173]  Hans-Jürgen Möller,et al.  Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up. , 2004, The Journal of clinical psychiatry.

[174]  G. Weniger,et al.  Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. , 2006, Journal of affective disorders.

[175]  Simon J Graham,et al.  Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. , 2005, Archives of general psychiatry.

[176]  Rupert Lanzenberger,et al.  Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders , 2010, The Journal of Neuroscience.

[177]  D. Nutt,et al.  Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression , 2009, European Neuropsychopharmacology.

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

[179]  A. Aleman,et al.  Regional brain volume in depression and anxiety disorders. , 2010, Archives of general psychiatry.

[180]  Lourdes Fañanás,et al.  5-HTTLPR Polymorphism of the Serotonin Transporter Gene Predicts Non-Remission in Major Depression Patients Treated With Citalopram in a 12-Weeks Follow Up Study , 2003, Journal of clinical psychopharmacology.

[181]  M E Raichle,et al.  Neuroanatomical circuits in depression: implications for treatment mechanisms. , 1992, Psychopharmacology bulletin.

[182]  Alan A. Wilson,et al.  Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study. , 2011, Journal of psychiatry & neuroscience : JPN.

[183]  Markus Kiefer,et al.  Executive control deficit in depression: event-related potentials in a Go/Nogo task , 2003, Psychiatry Research: Neuroimaging.

[184]  J. Hensler,et al.  Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration. , 2003, Life sciences.

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

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

[187]  Heather L. Urry,et al.  Failure to Regulate: Counterproductive Recruitment of Top-Down Prefrontal-Subcortical Circuitry in Major Depression , 2007, The Journal of Neuroscience.

[188]  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.

[189]  John Suckling,et al.  Neural responses to happy facial expressions in major depression following antidepressant treatment. , 2007, The American journal of psychiatry.

[190]  M. Lowe,et al.  Functional Connectivity in Single and Multislice Echoplanar Imaging Using Resting-State Fluctuations , 1998, NeuroImage.

[191]  I. Izquierdo,et al.  Acute treatment with the antidepressants bupropion and sertraline do not influence memory retrieval in man , 2006, European Archives of Psychiatry and Clinical Neuroscience.

[192]  Qiyong Gong,et al.  Resting-state functional connectivity in treatment-resistant depression. , 2011, The American journal of psychiatry.

[193]  Janaina Mourao-Miranda,et al.  Neural correlates of sad faces predict clinical remission to cognitive behavioural therapy in depression , 2009, Neuroreport.

[194]  R Todd Ogden,et al.  Lower serotonin transporter binding potential in the human brain during major depressive episodes. , 2006, The American journal of psychiatry.

[195]  Yves Chaput,et al.  Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: Electrophysiological studies in the rat brain , 1986, Naunyn-Schmiedeberg's Archives of Pharmacology.

[196]  Glenda M. MacQueen,et al.  Posterior Hippocampal Volumes Are Associated with Remission Rates in Patients with Major Depressive Disorder , 2008, Biological Psychiatry.

[197]  A. Coppen The Biochemistry of Affective Disorders , 1967, British Journal of Psychiatry.

[198]  Jun Liu,et al.  Reduced ventral anterior cingulate and amygdala volumes in medication-naïve females with major depressive disorder: A voxel-based morphometric magnetic resonance imaging study , 2007, Psychiatry Research: Neuroimaging.

[199]  Marco Cecchi,et al.  Serotonin Clearance In Vivo Is Altered to a Greater Extent by Antidepressant-Induced Downregulation of the Serotonin Transporter than by Acute Blockade of this Transporter , 2002, The Journal of Neuroscience.

[200]  D. Kupfer,et al.  Anatomic evaluation of the orbitofrontal cortex in major depressive disorder , 2004, Biological Psychiatry.

[201]  D. Pizzagalli,et al.  Functional but not structural subgenual prefrontal cortex abnormalities in melancholia , 2004 .

[202]  Peter Zwanzger,et al.  Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. , 2004, Archives of general psychiatry.

[203]  A. Serretti,et al.  Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients , 2007, Molecular Psychiatry.

[204]  Monte S. Buchsbaum,et al.  Effect of sertraline on regional metabolic rate in patients with affective disorder , 1997, Biological Psychiatry.

[205]  J. Newcomer,et al.  Effects of glucocorticoids on declarative memory function in major depression , 2004, Biological Psychiatry.

[206]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[207]  R Todd Constable,et al.  Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[208]  Philip K. McGuire,et al.  Prognostic prediction of therapeutic response in depression using high-field MR imaging , 2011, NeuroImage.

[209]  P. Fossati,et al.  Medial prefrontal cortex and the self in major depression. , 2011, Journal of affective disorders.

[210]  D. Drubach Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression , 2009 .

[211]  Brian Knutson,et al.  Neural Responses to Monetary Incentives in Major Depression , 2008, Biological Psychiatry.

[212]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[213]  Keith F. Tipton,et al.  The therapeutic potential of monoamine oxidase inhibitors , 2006, Nature Reviews Neuroscience.

[214]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[215]  Elizabeth A. Daubert,et al.  Serotonin: a regulator of neuronal morphology and circuitry , 2010, Trends in Neurosciences.

[216]  I. Gotlib,et al.  Attentional biases for negative interpersonal stimuli in clinical depression. , 2004, Journal of abnormal psychology.

[217]  Robert L. Royall,et al.  Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. , 2001, Archives of general psychiatry.

[218]  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.

[219]  Jair C. Soares,et al.  Smaller Cingulate Volumes in Unipolar Depressed Patients , 2006, Biological Psychiatry.

[220]  C. Nemeroff,et al.  Serotonin Transporter: A Potential Substrate in the Biology of Suicide , 2003, Neuropsychopharmacology.

[221]  Glenda M MacQueen,et al.  Magnetic resonance imaging and prediction of outcome in patients with major depressive disorder. , 2009, Journal of psychiatry & neuroscience : JPN.

[222]  R. DeRubeis,et al.  Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms , 2008, Nature Reviews Neuroscience.

[223]  A. Bossuyt,et al.  Dopamine D2 receptors in depression measured with single photon emission computed tomography , 1994, Biological Psychiatry.

[224]  M E Phelps,et al.  Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. , 2001, Archives of general psychiatry.

[225]  Yoshiro Okubo,et al.  High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. , 2003, Archives of general psychiatry.

[226]  P. Cowen,et al.  Diminished Neural Processing of Aversive and Rewarding Stimuli During Selective Serotonin Reuptake Inhibitor Treatment , 2010, Biological Psychiatry.

[227]  S. Lehéricy,et al.  Self-referential processing and the prefrontal cortex over the course of depression: a pilot study. , 2010, Journal of affective disorders.

[228]  Sylvain Houle,et al.  Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. , 2004, The American journal of psychiatry.

[229]  H. Feistel,et al.  Dopamine and depression — Striatal dopamine D2 receptor SPECT before and after antidepressant therapy , 1996, Psychopharmacology.

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

[231]  C. Naranjo,et al.  Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. , 2002, Archives of general psychiatry.

[232]  I. Gotlib,et al.  Selective attention to emotional faces following recovery from depression. , 2007, Journal of abnormal psychology.

[233]  Glyn Lewis,et al.  Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression , 2002, British Journal of Psychiatry.

[234]  J. Hirvonen,et al.  Effects of antidepressant drug treatment and psychotherapy on striatal and thalamic dopamine D2/3 receptors in major depressive disorder studied with [11C]raclopride PET , 2011, Journal of psychopharmacology.

[235]  T. Suslow,et al.  Detection of Facial Expressions of Emotions in Depression , 2001, Perceptual and motor skills.

[236]  G. Dichter,et al.  Affective context interferes with cognitive control in unipolar depression: an fMRI investigation. , 2009, Journal of affective disorders.

[237]  Nora D. Volkow,et al.  Functional connectivity hubs in the human brain , 2011, NeuroImage.

[238]  C. Otte,et al.  Cognitive Impairment in Major Depression: Association with Salivary Cortisol , 2009, Biological Psychiatry.

[239]  P. Koolschijn,et al.  Brain volume abnormalities in major depressive disorder: a Meta-analysis of magnetic resonance imaging studies , 2009, NeuroImage.

[240]  D. Levinson The Genetics of Depression: A Review , 2006, Biological Psychiatry.

[241]  Allison C. Nugent,et al.  Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder , 2011, NeuroImage.

[242]  K. Lesch,et al.  Integrating neurobiological markers of depression. , 2010, Archives of general psychiatry.

[243]  M. Lowe,et al.  Antidepressant Effect on Connectivity of the Mood-Regulating Circuit: An fMRI Study , 2005, Neuropsychopharmacology.

[244]  Time Course of In Vivo 5-HTT Transporter Occupancy by Fluvoxamine , 2006, Journal of clinical psychopharmacology.

[245]  M. Taylor,et al.  Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain , 2009, Neuroscience.

[246]  Robert B. Innis,et al.  Sex Differences in Diencephalon Serotonin Transporter Availability in Major Depression , 2006, Biological Psychiatry.

[247]  Luke Clark,et al.  Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression. , 2005, The American journal of psychiatry.

[248]  G. Pearlson,et al.  Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters , 2011, Psychological Medicine.

[249]  L. Parsons,et al.  Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. , 1999, The American journal of psychiatry.

[250]  Sylvain Houle,et al.  Novel 5-HTTLPR Allele Associates with Higher Serotonin Transporter Binding in Putamen: A [11C] DASB Positron Emission Tomography Study , 2007, Biological Psychiatry.

[251]  Jesús Pujol,et al.  Cross-Sectional and Longitudinal Assessment of Structural Brain Alterations in Melancholic Depression , 2011, Biological Psychiatry.

[252]  A. Schene,et al.  Evidence Why Paroxetine Dose Escalation is Not Effective in Major Depressive Disorder: A Randomized Controlled Trial With Assessment of Serotonin Transporter Occupancy , 2009, Neuropsychopharmacology.