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2. Publisher Correction: Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Author

Fu, Cynthia H. Y., Antoniades, Mathilde, Erus, Guray, Garcia, Jose A., Fan, Yong, Arnone, Danilo, Arnott, Stephen R., Chen, Taolin, Choi, Ki Sueng, Fatt, Cherise Chin, Frey, Benicio N., Frokjaer, Vibe G., Ganz, Melanie, Godlewska, Beata R., Hassel, Stefanie, Ho, Keith, McIntosh, Andrew M., Qin, Kun, Rotzinger, Susan, Sacchet, Matthew D., Savitz, Jonathan, Shou, Haochang, Singh, Ashish, Stolicyn, Aleks, Strigo, Irina, Strother, Stephen C., Tosun, Duygu, Victor, Teresa A., Wei, Dongtao, Wise, Toby, Zahn, Roland, Anderson, Ian M., Craighead, W. Edward, Deakin, J. F. William, Dunlop, Boadie W., Elliott, Rebecca, Gong, Qiyong, Gotlib, Ian H., Harmer, Catherine J., Kennedy, Sidney H., Knudsen, Gitte M., Mayberg, Helen S., Paulus, Martin P., Qiu, Jiang, Trivedi, Madhukar H., Whalley, Heather C., Yan, Chao-Gan, Young, Allan H., and Davatzikos, Christos

Published
2024
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3. Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder

Author

Bhattacharyya, Sudeepa, MahmoudianDehkordi, Siamak, Sniatynski, Matthew J., Belenky, Marina, Marur, Vasant R., Rush, A. John, Craighead, W. Edward, Mayberg, Helen S., Dunlop, Boadie W., Kristal, Bruce S., and Kaddurah-Daouk, Rima

Published
2025
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5. Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Author

Fu, Cynthia H. Y., Antoniades, Mathilde, Erus, Guray, Garcia, Jose A., Fan, Yong, Arnone, Danilo, Arnott, Stephen R., Chen, Taolin, Choi, Ki Sueng, Fatt, Cherise Chin, Frey, Benicio N., Frokjaer, Vibe G., Ganz, Melanie, Godlewska, Beata R., Hassel, Stefanie, Ho, Keith, McIntosh, Andrew M., Qin, Kun, Rotzinger, Susan, Sacchet, Matthew D., Savitz, Jonathan, Shou, Haochang, Singh, Ashish, Stolicyn, Aleks, Strigo, Irina, Strother, Stephen C., Tosun, Duygu, Victor, Teresa A., Wei, Dongtao, Wise, Toby, Zahn, Roland, Anderson, Ian M., Craighead, W. Edward, Deakin, J. F. William, Dunlop, Boadie W., Elliott, Rebecca, Gong, Qiyong, Gotlib, Ian H., Harmer, Catherine J., Kennedy, Sidney H., Knudsen, Gitte M., Mayberg, Helen S., Paulus, Martin P., Qiu, Jiang, Trivedi, Madhukar H., Whalley, Heather C., Yan, Chao-Gan, Young, Allan H., and Davatzikos, Christos

Published
2024
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9. Metabolomic and inflammatory signatures of symptom dimensions in major depression

Author

Brydges, Christopher R, Bhattacharyya, Sudeepa, Dehkordi, Siamak Mahmoudian, Milaneschi, Yuri, Penninx, Brenda, Jansen, Rick, Kristal, Bruce S, Han, Xianlin, Arnold, Matthias, Kastenmüller, Gabi, Bekhbat, Mandakh, Mayberg, Helen S, Craighead, W Edward, Rush, A John, Fiehn, Oliver, Dunlop, Boadie W, Kaddurah-Daouk, Rima, and Consortium, for the Mood Disorders Precision Medicine

Subjects
Depression, Mental Health, Brain Disorders, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Amino Acids, Depressive Disorder, Major, Fatty Acids, Nonesterified, Humans, Metabolomics, Anxiety, Inflammation, Mood Disorders Precision Medicine Consortium, Immunology, Neurosciences, Psychology, Neurology & Neurosurgery
Abstract

BackgroundMajor depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions.MethodsUsing three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism.ResultsThe IMD clinical dimension and the inflammatory index were positively correlated (r = 0.19, p = 0.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids.ConclusionThe IMD dimension of depression appears reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.

Published
2022

11. Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression

Author

MahmoudianDehkordi, Siamak, Ahmed, Ahmed T, Bhattacharyya, Sudeepa, Han, Xianlin, Baillie, Rebecca A, Arnold, Matthias, Skime, Michelle K, John-Williams, Lisa St, Moseley, M Arthur, Thompson, J Will, Louie, Gregory, Riva-Posse, Patricio, Craighead, W Edward, McDonald, William, Krishnan, Ranga, Rush, A John, Frye, Mark A, Dunlop, Boadie W, Weinshilboum, Richard M, and Kaddurah-Daouk, Rima

Subjects
Depression, Brain Disorders, Mental Health, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Mental health, Amines, Antidepressive Agents, Carnitine, Citalopram, Depressive Disorder, Major, Humans, Lipids, Selective Serotonin Reuptake Inhibitors, Mood Disorders Precision Medicine Consortium, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines-including arginine, proline, and methionine sulfoxide-were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (

Published
2021

12. Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature

Author

Brydges, Christopher R, Fiehn, Oliver, Mayberg, Helen S, Schreiber, Henry, Dehkordi, Siamak Mahmoudian, Bhattacharyya, Sudeepa, Cha, Jungho, Choi, Ki Sueng, Craighead, W Edward, Krishnan, Ranga R, Rush, A John, Dunlop, Boadie W, and Kaddurah-Daouk, Rima

Subjects
Neurosciences, Clinical Research, Complementary and Integrative Health, Anxiety Disorders, Behavioral and Social Science, Mental Health, Depression, Mental health, Adult, Aged, Anxiety, Biomarkers, Brain, Disease Susceptibility, Female, Functional Neuroimaging, Gastrointestinal Microbiome, Humans, Indican, Magnetic Resonance Imaging, Male, Metabolic Networks and Pathways, Metabolome, Metabolomics, Middle Aged, Symptom Assessment, Uremic Toxins, Young Adult, Mood Disorders Precision Medicine Consortium
Abstract

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite's effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.Clinical trial NCT00360399 "Predictors of Antidepressant Treatment Response: The Emory CIDAR" https://clinicaltrials.gov/ct2/show/NCT00360399 .

Published
2021

17. ERICH3: vesicular association and antidepressant treatment response

Author

Liu, Duan, Zhuang, Yongxian, Zhang, Lingxin, Gao, Huanyao, Neavin, Drew, Carrillo-Roa, Tania, Wang, Yani, Yu, Jia, Qin, Sisi, Kim, Daniel C., Liu, Erica, Nguyen, Thanh Thanh Le, Biernacka, Joanna M., Kaddurah-Daouk, Rima, Dunlop, Boadie W., Craighead, W. Edward, Mayberg, Helen S., Binder, Elisabeth B., Frye, Mark A., Wang, Liewei, and Weinshilboum, Richard M.

Published
2021
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19. Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes

Author

Ahmed, Ahmed T., MahmoudianDehkordi, Siamak, Bhattacharyya, Sudeepa, Arnold, Matthias, Liu, Duan, Neavin, Drew, Moseley, M. Arthur, Thompson, J. Will, Williams, Lisa St John, Louie, Gregory, Skime, Michelle K., Wang, Liewei, Riva-Posse, Patricio, McDonald, William M., Bobo, William V., Craighead, W. Edward, Krishnan, Ranga, Weinshilboum, Richard M., Dunlop, Boadie W., Millington, David S., Rush, A. John, Frye, Mark A., and Kaddurah-Daouk, Rima

Published
2020
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20. Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavioral Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder

Author

Bhattacharyya, Sudeepa, primary, MahmoudianDehkordi, Siamak, additional, Sniatynski, Matthew J, additional, Belenky, Marina, additional, Marur, Vasant R., additional, Rush, A. John, additional, Craighead, W. Edward, additional, Mayberg, Helen S., additional, Dunlop, Boadie W., additional, Kristal, Bruce S., additional, and Kaddurah-Daouk, Rima, additional

Published
2024
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22. The protective effects of Swedish COVID-19 pandemic strategies on adolescents' mental health : a longitudinal cohort study

Author

Lilja, Josefine L., Augustsson, Pia, Björk, Marcus Praetorius, Marteinsdottir, Ina, Craighead, W. Edward, Arnarson, Eirikur Orn, Sveinsdottir, Gudny, Wikberg, Carl, Lilja, Josefine L., Augustsson, Pia, Björk, Marcus Praetorius, Marteinsdottir, Ina, Craighead, W. Edward, Arnarson, Eirikur Orn, Sveinsdottir, Gudny, and Wikberg, Carl

Abstract

Aim: The aim of this study was to investigate a cohort of Swedish eighth graders' mental health and experiences during the COVID-19 pandemic.Methods: Participants were 157 eighth graders recruited in junior high schools during 2020 who completed a depression questionnaire and a survey about their psychosocial health in relation to the COVID-19 pandemic, alongside a follow-up assessment in 2021. Analyses were conducted using latent change score and cross-lagged models.Results: Participants' depressive symptoms did not substantially increase during the COVID-19 pandemic. The level of depressive symptoms in 2020 was significantly associated with participants' perceptions of the pandemic in 2020 and spring 2021. Participants with higher depression scores reported worse experiences of the pandemic.Conclusions: The stable level of depressive symptoms among this cohort of eighth graders suggested that keeping schools open during a nationwide lockdown could mitigate some mental health consequences. Adolescents in this study with higher self-assessed depressive symptoms were more likely to experience increased depression after 6 months and had worse experiences during the pandemic than others. This suggests that the pandemic may not immediately affect mental well-being, but those at risk may be affected over time.

Published
2024
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25. Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders

Author

Ahmed, Ahmed T., Frye, Mark A., Rush, A John, Biernacka, Joanna M., Craighead, W. Edward, McDonald, William M., Bobo, William V., Riva-Posse, Patricio, Tye, Susannah J., Mayberg, Helen S., Hall-Flavin, Daniel K., Skime, Michelle K., Jenkins, Greg D., Wang, Liewei, Krishnan, Ranga Rama, Weinshilboum, Richard M., Kaddurah-Daouk, Rima, and Dunlop, Boadie W.

Published
2018
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27. Combined effects of genotype and childhood adversity shape variability of DNA methylation across age

Author

Czamara, Darina, Tissink, Elleke, Tuhkanen, Johanna, Martins, Jade, Awaloff, Yvonne, Drake, Amanda J., Khulan, Batbayar, Palotie, Aarno, Winter, Sibylle M., Nemeroff, Charles B., Craighead, W. Edward, Dunlop, Boadie W., Mayberg, Helen S., Kinkead, Becky, Mathew, Sanjay J., Iosifescu, Dan V., Neylan, Thomas C., Heim, Christine M., Lahti, Jari, Eriksson, Johan G., Räikkönen, Katri, Ressler, Kerry J., Provençal, Nadine, and Binder, Elisabeth B.

Published
2021
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30. Psychotherapy or medication for depression? Using individual symptom meta-analyses to derive a Symptom-Oriented Therapy (SOrT) metric for a personalised psychiatry

Author

Kappelmann, Nils, Rein, Martin, Fietz, Julia, Mayberg, Helen S., Craighead, W. Edward, Dunlop, Boadie W., Nemeroff, Charles B., Keller, Martin, Klein, Daniel N., Arnow, Bruce A., Husain, Nusrat, Jarrett, Robin B., Vittengl, Jeffrey R., Menchetti, Marco, Parker, Gordon, Barber, Jacques P., Bastos, Andre G., Dekker, Jack, Peen, Jaap, Keck, Martin E., and Kopf-Beck, Johannes

Published
2020
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45. Treatment-Specific Hippocampal Subfield Volume Changes With Antidepressant Medication or Cognitive-Behavior Therapy in Treatment-Naive Depression

Author

Tai, Hua-Hsin, Cha, Jungho, Vedaei, Faezeh, Dunlop, Boadie W., Craighead, W. Edward, Mayberg, Helen S., and Choi, Ki Sueng

Subjects
cognitive behavioral theory, Psychiatry, Psychiatry and Mental health, hippocampal atrophy, nervous system, depression, RC435-571, antidepressant medication, hippocampal tail, Original Research
Abstract

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To understand the differential effects of CBT and ADM on the hippocampus, we investigated the volume alterations of hippocampal subfields with treatment, outcome, and chronicity in treatment-naïve depression patients.Methods: Treatment-naïve depressed patients from the PReDICT study were included in this analysis. A total of 172 patients who completed 12 weeks of randomized treatment with CBT (n = 45) or ADM (n = 127) were included for hippocampal subfield volume analysis. Forty healthy controls were also included for the baseline comparison. Freesurfer 6.0 was used to segment 26 hippocampal substructures and bilateral whole hippocampus from baseline and week 12 structural MRI scans. A generalized linear model with covariates of age and gender was used for group statistical tests. A linear mixed model for the repeated measures with covariates of age and gender was used to examine volumetric changes over time and the contributing effects of treatment type, outcome, and illness chronicity.Results: Of the 172 patients, 85 achieved remission (63/127 ADM, 22/45 CBT). MDD patients showed smaller baseline volumes than healthy controls in CA1, CA3, CA4, parasubiculum, GC-ML-DG, Hippocampal Amygdala Transition Area (HATA), and fimbria. Over 12 weeks of treatment, further declines in the volumes of CA1, fimbria, subiculum, and HATA were observed regardless of treatment type or outcome. CBT remitters, but not ADM remitters, showed volume reduction in the right hippocampal tail. Unlike ADM remitters, ADM non-responders had a decline in volume in the bilateral hippocampal tails. Baseline volume of left presubiculum (regardless of treatment type) and right fimbria and HATA in CBT patients were correlated with a continuous measure of clinical improvement. Chronicity of depression had no effect on any measures of hippocampal subfield volumes.Conclusion: Two first-line antidepressant treatments, CBT and ADM, have different effects on hippocampal tail after 12 weeks. This finding suggests that remission achieved via ADM may protect against progressive hippocampal atrophy by altering neuronal plasticity or supporting neurogenesis. Studies with multimodal neuroimaging, including functional and structural analysis, are needed to assess further the impact of two different antidepressant treatments on hippocampal subfields.

Published
2021
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46. Factor Analysis of the Children's Depression Inventory in a Community Sample.

Author

Craighead, W. Edward, Smucker, Mervin R., Wilcoxon Craighead, Linda, and Ilardi, Stephen S.

Abstract

The factor structure of the Children's Depression Inventory (CDI) (M. Kovacs, 1992) was evaluated in a community sample of 1777 children and 924 adolescents. There were five first-order factors for the child group, and the same five plus one more for the adolescents. Results support the stability and predictability of the obtained factor structures. (SLD)

Published
1998

49. Relationship of Children's Depression Inventory Factors to Major Depression among Adolescents.

Author

Craighead, W. Edward

Abstract

The relationship between Children's Depression Inventory (CDI) scores and major depression, conduct disorder, and anxiety disorders was studied for 107 psychiatric inpatients aged 12 to 18 years. Findings support total CDI score, rather than factor scores, as the most practical measure for classifying participants as depressed or not. (SLD)

Published
1995

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