Research information final report

Shared and Unique Changes in Brain Connectivity Among Depressed Patients After Remission With Pharmacotherapy Versus Psychotherapy • A total of 131 participants completed the treatment and provided valid MRI data at both the start and at week 12. Among them, 49.5% of those receiving medication and 47.5% of those undergoing cognitive behavioral therapy (CBT) reached remission. Both treatment arms showed a notable shared alteration in resting-state functional connectivity—specifically, a decrease in connectivity between the subcallosal cingulate (SCC) and the left medial motor cortex (mM1). Importantly, this neural change was present only in individuals who achieved remission and was absent in those who did not respond to treatment. • The researchers also identified changes that were specific to each treatment type. CBT remitters exhibited increased rsFC between the posterior cingulate cortex (PCC) and the superior frontal cortex, whereas medication remitters showed decreased connectivity between the PCC and the middle frontal cortex. Additionally, individuals who remitted with CBT had stronger connectivity within the executive control network (ECN) and the salience network (SN)—especially in areas related to attention regulation and cognitive control—compared with medication remitters and healthy participants. Medication remitters, on the other hand, did not differ significantly from healthy controls at week 12. • Figure 1: Panel A shows that both CBT and medication remitters demonstrated similar baseline-to-week-12 changes in resting-state functional connectivity (rsFC). The inset zooms in on the overlapping region within the medial motor cortex (mM1), indicating the voxels with significant rsFC changes for medication remitters (red) and CBT remitters (green), with shared areas in yellow. The violin plot shows that both groups had comparable reductions within this overlap cluster, and by week 12, SCC–mM1 connectivity in remitters was significantly lower than in healthy controls. Panel B presents SCC rsFC changes from baseline to week 12 for all CBT and medication completers, considering response status. Both treatments were associated with decreases in SCC–mM1 rsFC, but no voxel-level overlap emerged. The violin plots show no significant change in medication patients when examining the center of mass of the CBT-defined mM1 cluster, and no significant change in CBT patients when using the medication-defined mM1 cluster. Panel C highlights treatment-specific rsFC changes that differed significantly between CBT and medication remitters. • Figure 2: Panel A illustrates the rsFC changes observed among CBT remitters, and Panel B shows these changes for remitters treated with antidepressant medication. The schematic diagrams, informed by Figure 1 and Table S2, mark regions with significant connectivity changes in green. In both diagrams, a dark blue arc denotes reduced connectivity between the subcallosal cingulate (SCC) and the somatomotor cortex in remitters from both treatment groups. In the CBT diagram, red arcs indicate connectivity increases from baseline to week 12, whereas in the medication diagram, light blue arcs indicate decreases. Labeled regions include the anterior insula (ANT INS), dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC), and SCC. • Table 1 summarizes the baseline characteristics of participants in a study examining brain connectivity after remission from major depressive disorder following either antidepressant medication or cognitive-behavioral therapy (CBT). Tables S1–S4 in the online supplement show the permutation-based within-treatment changes in resting-state functional connectivity (rsFC) for patients who achieved remission with CBT or medication across the four seed regions. No statistically significant differences (all p > 0.2) were observed between the medication and CBT groups in any demographic or clinical measures. Likewise, there were no significant differences in age or sex between the major depression group and healthy controls. Abbreviations: CBT = cognitive-behavioral therapy; HAMD = Hamilton Depression Rating Scale; HAM-A = Hamilton Anxiety Rating Scale. • Table 2 displays the changes in resting-state functional connectivity between the subcallosal cingulate cortex and the medial motor cortex according to outcome group. • Table 3 lists the centers of mass and cluster sizes for each region. Green corresponds to CBT-treated patients, red to medication-treated patients, and blue to healthy controls. Solid green or red lines indicate statistically significant within-treatment changes (p < 0.005), while dashed lines indicate changes with p values between 0.005 and 0.05. Statistically significant differences between patients and healthy controls are shown by dotted (p < 0.05) or solid (p < 0.01) blue lines at the top of the plots. Differences between treatment groups at baseline or week 12 are marked by dotted (p < 0.05) or solid (p < 0.01) black lines at the bottom of the plots. Authors • Boadie DunlopDepartment of Psychiatry and Behavioral Sciencess Professor ➢ Co-Director, Emory Center for Psychedelics and Spirituality, Emory University ➢ Director, Adult Outpatient Programs, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine ➢ Professor, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine ➢ Medical Director, Emory Healthcare Veterans Program, Emory University ➢ Medical Director, Emory Veterans Program, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Publications: ➢ Rapid Effects of MDMA Administration on Self-Reported Personality Traits and Affect State: A Randomized, Placebo-Controlled Trial in Healthy Adults. ➢ Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort. ➢ A framework for assessment of adverse events occurring in psychedelicassisted therapies. ➢ The capacity of brain circuits to enhance psychiatry. ➢ The metabolome-wide signature of major depressive disorder. • Jungho Cha ➢ Nash Family Center for Advanced Circuit Therapeutics · Radiology PhD ➢ Indeks Hirsha20 Publications: ➢ Choroid Plexus Volume, Amyloid Burden, and Cognition in the Alzheimer's Disease Continuum ➢ Different effect of hypoand hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent? ➢ Whole brain network effects of subcallosal cingulate deep brain stimulation for treatment-resistant depression ➢ Cingulate dynamics track depression recovery with deep brain stimulation ➢ Distinct amyloid-dependent patterns of nigra dopamine depletion in Lewy body diseases • Ki Sueng Choi ➢ Icahn School of Medicine at Mount Sinai ➢ Index Hirsha – 32 Publications: ➢ Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression ➢ A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression ➢ Functional connectivity of the subcallosal cingulate cortex and differential outcomes to treatment with cognitive-behavioral therapy or antidepressant medication for major ➢ Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease • Justin K. Rajendra ➢ Staff – National Institute of Mental Health ➢ Index Hirsha - 15 Publications: ➢ Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression ➢ A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression ➢ Handling multiplicity in neuroimaging through Bayesian lenses with multilevel modeling ➢ Brain activation in primary motor and somatosensory cortices during motor imagery correlates with motor imagery ability in stroke patients • Charles B. Nemeroff ➢ Professor of Psychiatry, University of Texas at Austin Dell Medical School ➢ Index Hirsha – 188 Publications: ➢ The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies ➢ Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood ➢ Depression, desperation, and suicidal ideation in college students: results from the American Foundation for Suicide Prevention College Screening Project at Emory University • W. Edward Craighead ➢ Department of Psychiatry and Behavioral Sciences and Department of Psychology, Emory University Publications: ➢ Effects of exercise training on older patients with major depression ➢ Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months ➢ Normative and reliability data for the Children's Depression Inventory ➢ Neurobiological and psychiatric consequences of child abuse and neglect ➢ The role of nonspecific factors in cognitive-behavior therapy for depression. • Helen Mayberg MD ➢ Icahn School of Medicine at Mount Sinai ➢ Index Hirsha - 114 Publications: ➢ Deep brain stimulation for treatment-resistant depression ➢ Toward discovery science of human brain function ➢ Limbic-cortical dysregulation: a proposed model of depression. ➢ Attending to the present: mindfulness meditation reveals distinct neural modes of self-reference. About The American Journal of Psychiatry • The American Journal of Psychiatry is the world’s most widely read psychiatric jornual. Published monthly, it serves as a key source of up-to-date information for psychiatrists and other mental health professionals. No other publication in the field reaches as broad an audience with comparable influence or timeliness. It is consider indispensable by most practicing psychiatrists. The jornual was first published in 1844 under the name American Journal of Insanity, and it adopted its current title in July 1921. 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