A neurocognitive model for understanding treatment action in depression

The way in which emotion is represented and processed in the human brain is an expanding area of research and has key implications for how we understand and potentially treat affective disorders such as depression. Characterizing the effects of pharmacological manipulations of key neurotransmitter systems can also help reveal the neurochemical underpinnings of emotional processing and how common antidepressant drugs may work in the treatment of depression and anxiety. This approach has revealed that depression is associated with both neural and behavioural biases towards negative over positive stimuli. Evidence from pharmacological challenge studies suggests that antidepressant treatment acts to normalize these biases early on in treatment, resulting in patients experiencing the world in a more positive way, improving their mood over time. This model is supported by evidence from both pharmacological and non-pharmacological interventions. The unique perspective on antidepressant treatment offered by this approach provides some insights into individual response to treatment, as well as novel approaches to drug development.

[1]  Pienie Zwitserlood,et al.  Automatic Mood-Congruent Amygdala Responses to Masked Facial Expressions in Major Depression , 2010, Biological Psychiatry.

[2]  H. Sackeim,et al.  Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates , 2011, PloS one.

[3]  P. Cowen,et al.  Short-term antidepressant treatment modulates amygdala response to happy faces , 2009, Psychopharmacology.

[4]  K. Mogg,et al.  Implicit and explicit memory for emotion-congruent information in clinical depression and anxiety. , 1995, Behaviour research and therapy.

[5]  Daniella J. Furman,et al.  Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data. , 2012, The American journal of psychiatry.

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

[7]  A Frazer,et al.  Delayed pharmacological effects of antidepressants , 2002, Molecular Psychiatry.

[8]  P. Cowen,et al.  Effects of erythropoietin on emotional processing biases in patients with major depression: an exploratory fMRI study , 2009, Psychopharmacology.

[9]  C. Harmer Emotional processing and antidepressant action. , 2013, Current topics in behavioral neurosciences.

[10]  P. Cowen,et al.  Direct effects of diazepam on emotional processing in healthy volunteers , 2007, Psychopharmacology.

[11]  M. Terman,et al.  Controlled trial of naturalistic dawn simulation and negative air ionization for seasonal affective disorder. , 2006, The American journal of psychiatry.

[12]  C. Harmer,et al.  Erythropoietin Reduces Neural and Cognitive Processing of Fear in Human Models of Antidepressant Drug Action , 2007, Biological Psychiatry.

[13]  C. MacLeod,et al.  Selective attention and emotional vulnerability: assessing the causal basis of their association through the experimental manipulation of attentional bias. , 2002, Journal of abnormal psychology.

[14]  Patrick M Fisher,et al.  Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity , 2008, Neuropsychopharmacology.

[15]  B. Lebowitz,et al.  Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. , 2006, The American journal of psychiatry.

[16]  G. Dawson,et al.  Combined NK1 antagonism and serotonin reuptake inhibition: effects on emotional processing in humans , 2013, Journal of psychopharmacology.

[17]  M B Keller,et al.  Premorbid personality assessments of first onset of major depression. , 1989, Archives of general psychiatry.

[18]  Draulio B de Araujo,et al.  Effects of diazepam on BOLD activation during the processing of aversive faces , 2012, Journal of psychopharmacology.

[19]  D. Perrett,et al.  Acute SSRI Administration Affects the Processing of Social Cues in Healthy Volunteers , 2003, Neuropsychopharmacology.

[20]  A. Gibbs,et al.  Alpha 2B Adrenoceptor Genotype Moderates Effect of Reboxetine on Negative Emotional Memory Bias in Healthy Volunteers , 2013, The Journal of Neuroscience.

[21]  P. Cowen,et al.  Effect of acute antidepressant administration on negative affective bias in depressed patients. , 2009, The American journal of psychiatry.

[22]  Rebecca Elliott,et al.  Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study , 2007, Neuroreport.

[23]  P. Thuras,et al.  Emotion recognition processing as early predictor of response to 8‐week citalopram treatment in late‐life depression , 2014, International journal of geriatric psychiatry.

[24]  P. Cowen,et al.  Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers. , 2009, The international journal of neuropsychopharmacology.

[25]  S. Mineka,et al.  Elevated responding to safe conditions as a specific risk factor for anxiety versus depressive disorders: evidence from a longitudinal investigation. , 2012, Journal of abnormal psychology.

[26]  A. Bouhuys,et al.  Depressed patients' perceptions of facial emotions in depressed and remitted states are associated with relapse: a longitudinal study. , 1999, The Journal of nervous and mental disease.

[27]  P. Cowen,et al.  Effects of 7 days of treatment with the cannabinoid type 1 receptor antagonist, rimonabant, on emotional processing , 2012, Journal of psychopharmacology.

[28]  C. Harmer,et al.  Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism , 2013, Psychological Medicine.

[29]  Karin Mogg,et al.  Attentional Bias in Generalized Anxiety Disorder Versus Depressive Disorder , 2005, Cognitive Therapy and Research.

[30]  S. Preskorn,et al.  Demonstration of the Efficacy and Safety of a Novel Substance P (NK1) Receptor Antagonist in Major Depression , 2004, Neuropsychopharmacology.

[31]  Rebecca Elliott,et al.  The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study , 2005, Neuropsychopharmacology.

[32]  C. Guilleminault,et al.  Major depressive disorder, sleep EEG and agomelatine: an open-label study. , 2007, The international journal of neuropsychopharmacology.

[33]  Stella W. Y. Chan,et al.  Highly neurotic never-depressed students have negative biases in information processing , 2007, Psychological Medicine.

[34]  P. Cowen,et al.  Short-term NK1 receptor antagonism and emotional processing in healthy volunteers , 2011, Psychopharmacology.

[35]  P. Cowen,et al.  Antidepressant treatment and emotional processing: can we dissociate the roles of serotonin and noradrenaline? , 2013, Journal of psychopharmacology.

[36]  S. Becker,et al.  A model of hippocampal neurogenesis in memory and mood disorders , 2007, Trends in Cognitive Sciences.

[37]  J. Teasdale Cognitive Vulnerability to Persistent Depression , 1988 .

[38]  A. Serretti,et al.  Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy , 2012, European Neuropsychopharmacology.

[39]  C. Léránth,et al.  Short‐term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus , 2005, The European journal of neuroscience.

[40]  P. Cowen,et al.  Early effects of mirtazapine on emotional processing , 2009, Psychopharmacology.

[41]  J. Suvisaari,et al.  A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. , 2008, Journal of affective disorders.

[42]  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.

[43]  P. Cowen,et al.  NK1 receptor antagonism and the neural processing of emotional information in healthy volunteers. , 2009, The international journal of neuropsychopharmacology.

[44]  P. Cowen,et al.  Increased Positive versus Negative Affective Perception and Memory in Healthy Volunteers following Selective Serotonin and Norepinephrine Reuptake Inhibition , 2022 .

[45]  Guy M. Goodwin,et al.  Single dose antidepressant administration modulates the neural processing of self-referent personality trait words , 2007, NeuroImage.

[46]  C. Del Mar,et al.  Tryptophan and 5-hydroxytryptophan for depression. , 2001, The Cochrane database of systematic reviews.

[47]  Guy M. Goodwin,et al.  Antidepressant Drug Treatment Modifies the Neural Processing of Nonconscious Threat Cues , 2006, Biological Psychiatry.

[48]  O. Chelnokova,et al.  A single dose of antidepressant alters eye-gaze patterns across face stimuli in healthy women , 2014, Psychopharmacology.

[49]  D. Eyding,et al.  Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials , 2010, BMJ : British Medical Journal.

[50]  Thomas Elbert,et al.  A deletion variant of the α2b-adrenoceptor is related to emotional memory in Europeans and Africans , 2007, Nature Neuroscience.

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

[52]  A. Tutuş,et al.  The regional cerebral blood flow changes in major depressive disorder with and without psychotic features , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[53]  Karin Mogg,et al.  Selective orienting of attention to masked threat faces in social anxiety. , 2002, Behaviour research and therapy.

[54]  R. Elliott,et al.  Cognitive Mechanisms of Treatment in Depression , 2012, Neuropsychopharmacology.

[55]  P. Cowen,et al.  Dissociable effects of acute antidepressant drug administration on subjective and emotional processing measures in healthy volunteers , 2008, Psychopharmacology.

[56]  Francesco Fera,et al.  Dextroamphetamine Modulates the Response of the Human Amygdala , 2002, Neuropsychopharmacology.

[57]  P. Cowen,et al.  Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers , 2009, Psychopharmacology.

[58]  Paul M. Corballis,et al.  Effects of Subcallosal Cingulate Deep Brain Stimulation on Negative Self-bias in Patients With Treatment-resistant Depression , 2015, Brain Stimulation.

[59]  P. Cowen,et al.  The effects of reboxetine on emotional processing in healthy volunteers: an fMRI study , 2008, Molecular Psychiatry.

[60]  C. Grady,et al.  Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks , 2013, European Neuropsychopharmacology.

[61]  C. Harmer,et al.  Short-term antidepressant administration reduces negative self-referential processing in the medial prefrontal cortex in subjects at risk for depression , 2012, Molecular Psychiatry.

[62]  S. Stahl Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. , 1998, Journal of affective disorders.

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

[64]  Y. Ma,et al.  Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis , 2014, Molecular Psychiatry.

[65]  D. Saklofske,et al.  Neuroticism, depression, and depression proneness , 1995 .

[66]  K. Felmingham,et al.  The impact of 5-HTTLPR on acute serotonin transporter blockade by escitalopram on emotion processing: Preliminary findings from a randomised, crossover fMRI study , 2014, The Australian and New Zealand journal of psychiatry.

[67]  C. Harmer,et al.  ‘Can you look me in the face?' Short-term SSRI Administration Reverts Avoidant Ocular Face Exploration in Subjects at Risk for Psychopathology , 2014, Neuropsychopharmacology.

[68]  Jarmo Hietala,et al.  Lack of Efficacy of the Substance P (Neurokinin1 Receptor) Antagonist Aprepitant in the Treatment of Major Depressive Disorder , 2006, Biological Psychiatry.

[69]  P. Cowen,et al.  Toward a neuropsychological theory of antidepressant drug action: increase in positive emotional bias after potentiation of norepinephrine activity. , 2003, The American journal of psychiatry.

[70]  Guy M. Goodwin,et al.  Risk for depression is associated with neural biases in emotional categorisation , 2008, Neuropsychologia.

[71]  R. Blair,et al.  A comparison of the effects of a β-adrenergic blocker and a benzodiazepine upon the recognition of human facial expressions , 2002, Psychopharmacology.

[72]  J. Allmer,et al.  EPO Mediates Neurotrophic, Neuroprotective, Anti-Oxidant, and Anti-Apoptotic Effects via Downregulation of miR-451 and miR-885-5p in SH-SY5Y Neuron-Like Cells , 2014, Front. Immunol..

[73]  R. Blair,et al.  Selective impairment in the recognition of anger induced by diazepam , 1999, Psychopharmacology.

[74]  Matthew P. G. Allin,et al.  Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study , 2003, Neuroreport.

[75]  P. Cowen,et al.  A single dose of mirtazapine modulates neural responses to emotional faces in healthy people , 2010, Psychopharmacology.

[76]  P. Cowen,et al.  Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients , 2012, Psychological Medicine.

[77]  J. Bukh,et al.  Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial , 2014, Neuropsychopharmacology.

[78]  J. Sweeney,et al.  Cognitive impairments in depression. , 1989, Journal of affective disorders.

[79]  K. Mogg,et al.  Effect of short-term SSRI treatment on cognitive bias in generalised anxiety disorder , 2004, Psychopharmacology.

[80]  Dennis S. Charney,et al.  Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression , 2013, Biological Psychiatry.

[81]  N. Freemantle,et al.  Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. , 2006, Archives of general psychiatry.

[82]  W. Paulus,et al.  Effects of Frontal Transcranial Direct Current Stimulation on Emotional State and Processing in Healthy Humans , 2012, Front. Psychiatry.

[83]  E. Holmes,et al.  Using Attentional Bias Modification as a Cognitive Vaccine Against Depression , 2012, Biological Psychiatry.

[84]  Richard Tranter,et al.  The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. , 2009, Journal of affective disorders.

[85]  G. Griebel,et al.  Acute and chronic treatment with 5-HT reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents , 2005, Psychopharmacology.

[86]  Catherine J. Harmer,et al.  Tryptophan supplementation induces a positive bias in the processing of emotional material in healthy female volunteers , 2006, Psychopharmacology.

[87]  G. Dawson,et al.  Agomelatine facilitates positive versus negative affective processing in healthy volunteer models , 2011, Journal of psychopharmacology.

[88]  P. Cowen,et al.  A single dose of citalopram increases fear recognition in healthy subjects , 2007, Journal of psychopharmacology.

[89]  T. Peters,et al.  Allowing for non-adherence to treatment in a randomized controlled trial of two antidepressants (citalopram versus reboxetine): an example from the GENPOD trial , 2014, Psychological Medicine.

[90]  P. Cowen,et al.  Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine , 2012, Journal of psychopharmacology.

[91]  P. Cowen,et al.  Frontal Cortex Stimulation Reduces Vigilance to Threat: Implications for the Treatment of Depression and Anxiety , 2016, Biological Psychiatry.

[92]  Ian M. Anderson,et al.  The effect of acute citalopram on face emotion processing in remitted depression: A pharmacoMRI study , 2011, European Neuropsychopharmacology.

[93]  D. Kupfer,et al.  Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. , 2006, The American journal of psychiatry.

[94]  Robin Christensen,et al.  Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials , 2007, The Lancet.

[95]  C. Beevers,et al.  Neural mechanisms of the cognitive model of depression , 2011, Nature Reviews Neuroscience.

[96]  Clare E Mackay,et al.  Short-term antidepressant treatment and facial processing , 2007, British Journal of Psychiatry.

[97]  F. Fregni,et al.  Enhancement of Affective Processing Induced by Bifrontal Transcranial Direct Current Stimulation in Patients With Major Depression , 2014, Neuromodulation : journal of the International Neuromodulation Society.

[98]  A. Cattaneo,et al.  Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants , 2009, BMC Neuroscience.

[99]  A. Beekman,et al.  Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). , 2011, The Journal of clinical psychiatry.

[100]  K. Douglas,et al.  Processing of Facial Emotion Expression in Major Depression: A Review , 2010, The Australian and New Zealand journal of psychiatry.

[101]  F. Fregni,et al.  Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. , 2014, The international journal of neuropsychopharmacology.

[102]  P. Cowen,et al.  NK1 receptor antagonism and emotional processing in healthy volunteers , 2010, Journal of psychopharmacology.

[103]  D. Luckenbaugh,et al.  A double-blind, placebo-controlled study of memantine in the treatment of major depression. , 2006, The American journal of psychiatry.

[104]  John R Geddes,et al.  Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic , 2014, Journal of psychopharmacology.

[105]  P. Cowen,et al.  Negative ion treatment increases positive emotional processing in seasonal affective disorder , 2011, Psychological Medicine.

[106]  R. Wise,et al.  Erythropoietin Improves Mood and Modulates the Cognitive and Neural Processing of Emotion 3 Days Post Administration , 2008, Neuropsychopharmacology.