Shared and Unique Changes in Brain Connectivity Among Depressed Patients After Remission With Pharmacotherapy Versus Psychotherapy.

OBJECTIVE The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication. METHODS The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30-60 mg/day or escitalopram 10-20 mg/day). Resting-state functional MRI scans were performed at baseline and at week 12. The primary outcome was change in the whole-brain rsFC of four seeded brain networks among participants who achieved remission. RESULTS Of the 131 completers with usable MRI data (74 female; mean age, 39.8 years), remission was achieved by 19 of 40 CBT-treated and 45 of 91 medication-treated patients. Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions. CONCLUSIONS Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches. Medication is associated with broadly inhibitory effects. In CBT remitters, the increase in rsFC strength between networks involved in cognitive control and attention provides biological support for the theorized mechanism of CBT. Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication.

[1]  P. Strick,et al.  The Cortical Motor Areas and the Emergence of Motor Skills: A Neuroanatomical Perspective. , 2021, Annual review of neuroscience.

[2]  Chaogan Yan,et al.  Eight‐week antidepressant treatment reduces functional connectivity in first‐episode drug‐naïve patients with major depressive disorder , 2021, Human brain mapping.

[3]  M. Mehta,et al.  Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review , 2021, Brain and neuroscience advances.

[4]  Jonathan D. Power,et al.  Rapid Precision Functional Mapping of Individuals Using Multi-Echo fMRI , 2020, Cell reports.

[5]  J. Andrews-Hanna,et al.  Transdiagnostic and disease-specific abnormalities in the default-mode network hubs in psychiatric disorders: A meta-analysis of resting-state functional imaging studies , 2020, European Psychiatry.

[6]  Harry Rubin-Falcone,et al.  Depression-related anterior cingulate prefrontal resting state connectivity normalizes following cognitive behavioral therapy , 2020, European Psychiatry.

[7]  Joseph M. Andreano,et al.  The tenacious brain: How the anterior mid-cingulate contributes to achieving goals , 2019, Cortex.

[8]  P. Strick,et al.  The mind–body problem: Circuits that link the cerebral cortex to the adrenal medulla , 2019, Proceedings of the National Academy of Sciences.

[9]  L. Williams,et al.  Intrinsic connectomes are a predictive biomarker of remission in major depressive disorder , 2019, Molecular Psychiatry.

[10]  I. Gotlib,et al.  Depression: A cognitive perspective. , 2019, Clinical psychology review.

[11]  C. Nemeroff,et al.  Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression. , 2019, The American journal of psychiatry.

[12]  Yogesh Rathi,et al.  Limits and reproducibility of resting-state functional MRI definition of DLPFC targets for neuromodulation , 2019, Brain Stimulation.

[13]  Y. Theodorakis,et al.  Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta‐analysis , 2018, Depression and anxiety.

[14]  L. Carpenter,et al.  Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[15]  C. Soriano-Mas,et al.  Emotion regulation in mood and anxiety disorders: A meta-analysis of fMRI cognitive reappraisal studies , 2017, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[16]  Guo-Rong Wu,et al.  Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment? , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[17]  Li Wang,et al.  Differential effects of antidepressant treatment on long-range and short-range functional connectivity strength in patients with major depressive disorder , 2017, Scientific Reports.

[18]  Helen S Mayberg,et al.  Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder. , 2017, The American journal of psychiatry.

[19]  Helen S Mayberg,et al.  Effects of Patient Preferences on Outcomes in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) Study. , 2017, The American journal of psychiatry.

[20]  H J Aizenstein,et al.  Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters , 2016, Molecular Psychiatry.

[21]  E. Rolls Functions of the anterior insula in taste, autonomic, and related functions , 2016, Brain and Cognition.

[22]  Patrice Péran,et al.  Structural–functional brain changes in depressed patients during and after electroconvulsive therapy , 2016, Acta Neuropsychiatrica.

[23]  E. Gudayol-Ferré,et al.  Changes in brain connectivity related to the treatment of depression measured through fMRI: a systematic review , 2015, Front. Hum. Neurosci..

[24]  David C. Mohr,et al.  Baseline Depression Severity as Moderator of Depression Outcomes Between Cognitive Behavioral Therapy vs Pharmacotherapy: An Individual Patient Data Meta-analysis. , 2015, JAMA psychiatry.

[25]  J. P. Hamilton,et al.  Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience , 2015, Biological Psychiatry.

[26]  Alessandro Sale,et al.  Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex , 2015, Scientific Reports.

[27]  J. Andrews-Hanna,et al.  Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity. , 2015, JAMA psychiatry.

[28]  Peng Liu,et al.  Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine , 2015, BMC Psychiatry.

[29]  Li Wang,et al.  The effects of antidepressant treatment on resting‐state functional brain networks in patients with major depressive disorder , 2015, Human brain mapping.

[30]  L. Uddin Salience processing and insular cortical function and dysfunction , 2014, Nature Reviews Neuroscience.

[31]  C. Reynolds,et al.  Resting state functional connectivity and treatment response in late-life depression , 2013, Psychiatry Research: Neuroimaging.

[32]  Karl J. Friston,et al.  A Treatment-Resistant Default Mode Subnetwork in Major Depression , 2013, Biological Psychiatry.

[33]  Bradley S Peterson,et al.  Antidepressants normalize the default mode network in patients with dysthymia. , 2013, JAMA psychiatry.

[34]  Helen S Mayberg,et al.  Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial , 2012, Trials.

[35]  M. Keller,et al.  Recovery and subsequent recurrence in patients with recurrent major depressive disorder. , 2012, Journal of psychiatric research.

[36]  P. Cowen,et al.  A cognitive neuropsychological model of antidepressant drug action , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[37]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[38]  Clement Hamani,et al.  The Subcallosal Cingulate Gyrus in the Context of Major Depression , 2011, Biological Psychiatry.

[39]  M. Mintun,et al.  Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus , 2010, Proceedings of the National Academy of Sciences.

[40]  R. DeRubeis,et al.  Prediction of response to medication and cognitive therapy in the treatment of moderate to severe depression. , 2009, Journal of consulting and clinical psychology.

[41]  M. Mintun,et al.  The default mode network and self-referential processes in depression , 2009, Proceedings of the National Academy of Sciences.

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

[43]  Stafford L. Lightman,et al.  The HPA axis in major depression: classical theories and new developments , 2008, Trends in Neurosciences.

[44]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[45]  L. Maffei,et al.  The Antidepressant Fluoxetine Restores Plasticity in the Adult Visual Cortex , 2008, Science.

[46]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[47]  Sidney H. Kennedy,et al.  Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. , 2007, The American journal of psychiatry.

[48]  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.

[49]  J. Markowitz,et al.  Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not. , 2005, Archives of general psychiatry.

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

[51]  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.

[52]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[53]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.