Jeffrey Miller, M.D.

Dr. Jeffrey Miller is Associate Professor of Clinical Psychiatry at Columbia University and Director of Brain Imaging in the Molecular Imaging and Neuropathology (MIND) Area. He conducts multimodal brain imaging research investigating biological correlates of depression and suicide risk using Positron Emission Tomography (PET) and magnetic resonance imaging (MRI).  In addition, he studies the use of brain imaging to predict treatment outcome, with a long-term goal of contributing to personalized medicine in psychiatry.  Dr. Miller is co-Investigator on the Conte Center for Suicide Prevention Project 3, ” PET Neuroimaging in Vivo in Mood Disorders and Suicidal Behavior”.

Research Focus

Dr. Miller has investigated pathophysiology in major depressive disorder using PET imaging to quantify relevant neurochemical systems, including the serotonin and kappa opioid neurotransmitter systems. He has conducted studies related to the pathophysiology of major depressive disorder, using PET imaging to focus on the serotonin and kappa opioid neurotransmitter systems. With colleagues, he has found consistent and replicated evidence of trait abnormalities of elevated 5-HT1A receptor binding in major depressive disorder, that are present both during active illness as well as during periods of sustained remission. He conducted the first study quantifying the kappa opioid receptor in major depressive disorder, identifying a trend-level relationship between kappa opioid receptor binding and activation of the hypothalamic-pituitary-adrenal axis. Through this Conte Center Award, he is investigating markers of neuroinflammation and of neurotransmitter catabolism in the pathophysiology of depression and suicide risk.

Identifying predictors of treatment outcome in psychiatry is an urgent clinical issue given the inadequate response and remission rates to existing treatments, the limited ability that clinicians have presently to predict treatment outcome, and the high morbidity that results from ineffectively treated illness. Dr. Miller’s work has used PET imaging to identify serotonergic abnormalities that predict better response to serotonergic antidepressants. He has also identified predictors of outcome to medication-based and psychotherapeutic treatment for depression using functional MRI and diffusion tensor imaging.

Select Publications

1.     Pantazatos SP, Ogden T, Melhem NM, Brent DA, Lesanpezeshki M, Burke A, Keilp JG, Miller JM, Mann JJ. Smaller cornu ammonis (CA3) as a potential risk factor for suicidal behavior in mood disorders. Journal of Psychiatric Research (2023); 163: 262-269. PMID: 37244064. DOI: 10.1016/j.jpsychires.2023.05.051

2.     Galfalvy H, Shea E, de Vegvar J, Pantazatos S, Huang Y-Y, Burke AK, Subletee ME, Oquendo MA, Zanderigo F, Miller JM, Mann JJ.  Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression. British Journal of Psychiatry (2023); 223(3): 415-421. PMID: 37395098. DOI: 10.1192/bjp.2023.13

3.     Bartlett EA, Zanderigo F, Stanley B, Choo TH, Galfalvy HC, Pantazatos SP, Sublette ME, Miller JM, Oquendo MA, Mann JJ.  In vivo serotonin transporter and 1A receptor binding potential and ecological momentary assessment (EMA) of stress in major depression and suicidal behavior. European Neuropsychopharmacology (2023); 70:1-13. doi: 10.1016/j.euroneuro.2023.01.006. PMID: 36780841.

4.     Pantazatos SP, Melhem NM, Brent DA, Zanderigo F, Bartlett EA, Lesanpezeshki M, Burke A, Miller JM, Mann JJ.  Ventral prefrontal serotonin 1A receptor binding: a neural marker of vulnerability for mood disorder and suicidal behavior? Mol Psychiatry (2022). PMID: 35760877. 

5. Bartlett EA, Zanderigo F, Stanley B, et al. In vivo serotonin transporter and 1A receptor binding potential and ecological momentary assessment (EMA) of stress in major depression and suicidal behavior. Eur Neuropsychopharmacol. 2023;70:1-13.

6. Rizk MM, Galfalvy H, Miller JM, et al. Characteristics of depressed suicide attempters with remitted substance use disorders. J Psychiatr Res. 2021;137:572-578.

7. Oquendo MA, Galfalvy HC, Choo TH, et al. Highly variable suicidal ideation: a phenotypic marker for stress induced suicide risk. Mol Psychiatry. 2021;26(9):5079-5086.

8. Schneck N, Tu T, Falcone HR, et al. Large-scale network dynamics in neural response to emotionally negative stimuli linked to serotonin 1A binding in major depressive disorder. Mol Psychiatry. 2021;26(6):2393-2401.

9. Cheung S, Goldenthal AR, Uhlemann A-C, Mann JJ, Miller JM, Sublette E. Systematic Review of Gut Microbiota and Major Depression.  Frontiers in Psychiatry, section Mood and Anxiety Disorders (2019): in press.

10. Rubin-Falcone H, Weber J, Kishon R, Ochsner K, Delaparte L, Doré B, Raman S, Denny BT, Oquendo MA, Mann JJ, Miller JM. Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation. Psychological Medicine (2019); 11: 1-15.

11. Miller JM, Zanderigo F, Purushothaman PD, DeLorenzo C, Rubin-Falcone H, Ogden RT, Keilp J, Oquendo MA, Nabulsi N, Huang YH, Parsey RV, Carson RE, Mann JJ. Kappa Opioid Receptor Binding in Major Depression: A Pilot Study. Synapse (2018); 72(9): e22042.

12. Rubin-Falcone H, Weber J, Kishon R, Ochsner K, Delaparte L, Doré B, Zanderigo F, Oquendo MA, Mann JJ, Miller JM. Longitudinal effects of cognitive behavioral therapy for depression on the neural correlates of emotion regulation. Psychiatry Research: Neuroimaging (2018); 271: 82-90.

13. Milak MS, Pantazatos S, Rashid R, Zanderigo F, Delorenzo C, Hesselgrave N, Ogden RT, Oquendo MA, Mulhern ST, Miller JM, Burke AK, Parsey RV, Mann JJ. Higher 5-HT1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk offspring – A pilot study. Psychiatry Research: Neuroimaging (2018); 276: 15-23.

14. Zanderigo F, Pantazatos S, Rubin-Falcon H, Ogden RT, Chhetry BT, Sullivan G, Oquendo M, Miller JM, Mann JJ. In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder. Brain Struct Funct (2018); 223(6):2609-2625

15. Rubin-Falcone H, Zanderigo F, Thapa-Chhetry B, Lan M, Miller JM, Sublette ME, Oquendo MA, Hellerstein DJ, McGrath PJ, Stewart JW, Mann JJ. Pattern recognition of magnetic resonance imaging-based gray matter volume measurements classifies bipolar disorder and major depressive disorder. Journal of Affective Disorders (2018); 227: 498-505.

16. Metts AV, Keilp JG, Oquendo MA, Mann JJ, Miller JM. Neurocognitive performance predicts treatment outcome with cognitive behavioral therapy for major depressive disorder.  Psychiatry Research (2018); 269: 376-385. PMID: 30173044.