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  1. Article ; Online: Orbitofrontal Cortex: A 'Non-rewarding' New Treatment Target in Depression?

    Downar, Jonathan

    Current biology : CB

    2019  Volume 29, Issue 2, Page(s) R59–R62

    Abstract: Self-perpetuating activity in lateral orbitofrontal regions has been theorized to sustain the negative thoughts and emotions of depression. A new study demonstrates that disrupting such activity may yield rapid improvements in mood state, pointing the ... ...

    Abstract Self-perpetuating activity in lateral orbitofrontal regions has been theorized to sustain the negative thoughts and emotions of depression. A new study demonstrates that disrupting such activity may yield rapid improvements in mood state, pointing the way to novel treatment strategies.
    MeSH term(s) Depression ; Electric Stimulation ; Humans ; Magnetic Resonance Imaging ; Prefrontal Cortex ; Reward
    Language English
    Publishing date 2019-01-19
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2018.11.057
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3208: Show issues Location:
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  2. Article ; Online: Orbitofrontal Cortex: A 'Non-rewarding' New Treatment Target in Depression?

    Downar, Jonathan

    Current biology : CB

    2019  Volume 29, Issue 5, Page(s) 896

    Language English
    Publishing date 2019-03-05
    Publishing country England
    Document type Published Erratum
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2019.02.015
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  3. Article ; Online: Deep Brain Stimulation in Depression: Even if Successful, Will It Ever Be Scalable?

    Downar, Jonathan

    Clinical pharmacology and therapeutics

    2019  Volume 106, Issue 4, Page(s) 709–711

    MeSH term(s) Cognitive Dysfunction/etiology ; Cognitive Dysfunction/prevention & control ; Deep Brain Stimulation/adverse effects ; Deep Brain Stimulation/methods ; Deep Brain Stimulation/statistics & numerical data ; Depressive Disorder, Major/epidemiology ; Depressive Disorder, Major/psychology ; Depressive Disorder, Major/therapy ; Humans ; Prevalence ; Suicide/prevention & control ; Treatment Outcome
    Language English
    Publishing date 2019-09-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.1572
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    Zs.A 20: Show issues Location:
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  4. Article ; Online: Dimensional and Categorical Solutions to Parsing Depression Heterogeneity in a Large Single-Site Sample.

    Dunlop, Katharine / Grosenick, Logan / Downar, Jonathan / Vila-Rodriguez, Fidel / Gunning, Faith M / Daskalakis, Zafiris J / Blumberger, Daniel M / Liston, Conor

    Biological psychiatry

    2024  

    Abstract: Background: Recent studies have reported significant advances in modeling the biological basis of heterogeneity in major depressive disorder, but investigators have also identified important technical challenges, including scanner-related artifacts, a ... ...

    Abstract Background: Recent studies have reported significant advances in modeling the biological basis of heterogeneity in major depressive disorder, but investigators have also identified important technical challenges, including scanner-related artifacts, a propensity for multivariate models to overfit, and a need for larger samples with more extensive clinical phenotyping. The goals of the current study were to evaluate dimensional and categorical solutions to parsing heterogeneity in depression that are stable and generalizable in a large, single-site sample.
    Methods: We used regularized canonical correlation analysis to identify data-driven brain-behavior dimensions that explain individual differences in depression symptom domains in a large, single-site dataset comprising clinical assessments and resting-state functional magnetic resonance imaging data for 328 patients with major depressive disorder and 461 healthy control participants. We examined the stability of clinical loadings and model performance in held-out data. Finally, hierarchical clustering on these dimensions was used to identify categorical depression subtypes.
    Results: The optimal regularized canonical correlation analysis model yielded 3 robust and generalizable brain-behavior dimensions that explained individual differences in depressed mood and anxiety, anhedonia, and insomnia. Hierarchical clustering identified 4 depression subtypes, each with distinct clinical symptom profiles, abnormal resting-state functional connectivity patterns, and antidepressant responsiveness to repetitive transcranial magnetic stimulation.
    Conclusions: Our results define dimensional and categorical solutions to parsing neurobiological heterogeneity in major depressive disorder that are stable, generalizable, and capable of predicting treatment outcomes, each with distinct advantages in different contexts. They also provide additional evidence that regularized canonical correlation analysis and hierarchical clustering are effective tools for investigating associations between functional connectivity and clinical symptoms.
    Language English
    Publishing date 2024-01-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2024.01.012
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    Zs.A 720: Show issues Location:
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  5. Article ; Online: Clinical outcomes in adolescents undergoing sequential bilateral 1 Hz/20 Hz transcranial magnetic stimulation for treatment resistant depression.

    Croarkin, Paul E / Zuckerman, Seth / Middleton, Victoria J / Monira, Naima / Kriske, Joseph / Bowman, Jennifer / Kriske, John / Donachie, Nancy / Downar, Jonathan

    Brain stimulation

    2024  Volume 17, Issue 2, Page(s) 431–433

    MeSH term(s) Humans ; Transcranial Magnetic Stimulation/methods ; Adolescent ; Depressive Disorder, Treatment-Resistant/therapy ; Male ; Female ; Treatment Outcome
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2394410-9
    ISSN 1876-4754 ; 1935-861X
    ISSN (online) 1876-4754
    ISSN 1935-861X
    DOI 10.1016/j.brs.2024.03.018
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  6. Article ; Online: Accelerated 1 Hz dorsomedial prefrontal transcranial magnetic stimulation for generalized anxiety disorder in adolescents and young adults: A case series.

    Croarkin, Paul E / Dojnov, Aleksandra / Middleton, Victoria J / Bowman, Jennifer / Kriske, Joseph / Donachie, Nancy / Siddiqi, Shan H / Downar, Jonathan

    Brain stimulation

    2024  Volume 17, Issue 2, Page(s) 269–271

    MeSH term(s) Humans ; Transcranial Magnetic Stimulation/methods ; Prefrontal Cortex/physiology ; Prefrontal Cortex/physiopathology ; Adolescent ; Male ; Young Adult ; Anxiety Disorders/therapy ; Female ; Adult ; Treatment Outcome
    Language English
    Publishing date 2024-03-03
    Publishing country United States
    Document type Letter ; Case Reports
    ZDB-ID 2394410-9
    ISSN 1876-4754 ; 1935-861X
    ISSN (online) 1876-4754
    ISSN 1935-861X
    DOI 10.1016/j.brs.2024.02.018
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  7. Article ; Online: Accelerated transcranial magnetic stimulation for psychological distress in advanced cancer: A phase 2a feasibility and preliminary efficacy clinical trial.

    Downar, James / Lapenskie, Julie / Anderson, Koby / Edwards, Jodi / Watt, Christine / Dionne, Michel / Rice, Jill / Kabir, Monisha / Lawlor, Peter / Downar, Jonathan

    Palliative medicine

    2024  Volume 38, Issue 4, Page(s) 485–491

    Abstract: Background: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for refractory ...

    Abstract Background: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for refractory depression, but no previous study has used rTMS to treat psychological or existential distress in the palliative setting.
    Aim: To determine whether a 5-day course of "accelerated" rTMS is feasible and can improve psychological and/or existential distress in a palliative care setting.
    Design: Open-label, single arm, feasibility, and preliminary efficacy study of intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex, 600 pulses/session, 8 sessions/day (once per hour) for 5 days. The outcomes were the rates of recruitment, completion of intervention, and follow-up (Feasibility); and the proportion of participants achieving 50% improvement on the Hamilton Depression Rating Scale (HDRS) or Hospital Anxiety and Depression Scale (HADS) 2 weeks post-treatment (Preliminary Efficacy).
    Setting/participants: Adults admitted to our academic Palliative Care Unit with advanced illness, life expectancy >1 month and psychological distress.
    Results: Due to COVID-19 pandemic-related interruptions, a total of nine participants were enrolled between August 2021 and April 2023. Two withdrew before starting rTMS, one stopped due to clinical deterioration unrelated to rTMS, and six completed the rTMS treatment. Five of six participants had a >50% improvement in HDRS, HADS-Anxiety, or both between baseline and the 2 week follow up; the sixth died prior to the 2-week follow-up. In this small sample, mean depression scores decreased from baseline to 2 weeks post-treatment (HDRS 18 vs 7,
    Conclusions: Accelerated rTMS improved symptoms of depression, anxiety, or both in this small feasibility and preliminary efficacy study. A larger, sham-controlled study is warranted to determine whether rTMS could be an effective, acceptable, and scalable treatment in the palliative setting.
    Trial registration: NCT04257227.
    MeSH term(s) Adult ; Humans ; Transcranial Magnetic Stimulation/adverse effects ; Treatment Outcome ; Feasibility Studies ; Pandemics ; Neoplasms
    Language English
    Publishing date 2024-03-14
    Publishing country England
    Document type Clinical Trial, Phase II ; Journal Article
    ZDB-ID 639247-7
    ISSN 1477-030X ; 0269-2163
    ISSN (online) 1477-030X
    ISSN 0269-2163
    DOI 10.1177/02692163241234799
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    Zs.A 2285: Show issues Location:
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  8. Article ; Online: Identifying Prefrontal Networks for Disease Vulnerability Versus Acute Illness in Major Depression.

    Fettes, Peter W / Downar, Jonathan

    Biological psychiatry. Cognitive neuroscience and neuroimaging

    2018  Volume 3, Issue 4, Page(s) 308–310

    MeSH term(s) Depressive Disorder, Major ; Disease Susceptibility ; Humans ; Prefrontal Cortex
    Language English
    Publishing date 2018-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2879089-3
    ISSN 2451-9030 ; 2451-9022
    ISSN (online) 2451-9030
    ISSN 2451-9022
    DOI 10.1016/j.bpsc.2018.02.004
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  9. Article ; Online: Retreatment with theta burst stimulation (TBS) for late life depression (LLD): A retrospective chart review.

    Lee, Hyewon H / Trevizol, Alisson P / Mulsant, Benoit H / Rajji, Tarek K / Downar, Jonathan / Daskalakis, Zafiris J / Blumberger, Daniel M

    Journal of psychiatric research

    2023  Volume 164, Page(s) 454–457

    MeSH term(s) Humans ; Depression/therapy ; Transcranial Magnetic Stimulation ; Retrospective Studies ; Depressive Disorder, Major ; Theta Rhythm/physiology ; Retreatment ; Treatment Outcome
    Language English
    Publishing date 2023-07-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3148-3
    ISSN 1879-1379 ; 0022-3956
    ISSN (online) 1879-1379
    ISSN 0022-3956
    DOI 10.1016/j.jpsychires.2023.06.040
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  10. Article ; Online: Accelerated Repetitive Transcranial Magnetic Stimulation to Treat Major Depression: The Past, Present, and Future.

    Chen, Leo / Klooster, Deborah C W / Tik, Martin / Thomas, Elizabeth H X / Downar, Jonathan / Fitzgerald, Paul B / Williams, Nolan R / Baeken, Chris

    Harvard review of psychiatry

    2023  Volume 31, Issue 3, Page(s) 142–161

    Abstract: Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based therapy for treatment-resistant major depressive disorder. A conventional course of rTMS applies 20-30 daily sessions over 4-6 weeks. The schedule of rTMS delivery can ...

    Abstract Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based therapy for treatment-resistant major depressive disorder. A conventional course of rTMS applies 20-30 daily sessions over 4-6 weeks. The schedule of rTMS delivery can be accelerated by applying multiple stimulation sessions per day, which reduces the duration of a treatment course with a predefined number of sessions. Accelerated rTMS reduces time demands, improves clinical efficiency, and potentially induces faster onset of antidepressant effects. However, considerable heterogeneity exists across study designs. Stimulation protocols vary in parameters such as the stimulation target, frequency, intensity, number of pulses applied per session or over a course of treatment, and duration of intersession intervals. In this article, clinician-researchers and neuroscientists who have extensive research experience in accelerated rTMS synthesize a consensus based on two decades of investigation and development, from early studies ("Past") to contemporaneous theta burst stimulation, a time-efficient form of rTMS gaining acceptance in clinical settings ("Present"). We propose descriptive nomenclature for accelerated rTMS, recommend avenues to optimize therapeutic and efficiency potential, and suggest using neuroimaging and electrophysiological biomarkers to individualize treatment protocols ("Future"). Overall, empirical studies show that accelerated rTMS protocols are well tolerated and not associated with serious adverse effects. Importantly, the antidepressant efficacy of accelerated rTMS appears comparable to conventional, once daily rTMS protocols. Whether accelerated rTMS induces antidepressant effects more quickly remains uncertain. On present evidence, treatment protocols incorporating high pulse dose and multiple treatments per day show promise and improved efficacy.
    MeSH term(s) Humans ; Depressive Disorder, Major/drug therapy ; Transcranial Magnetic Stimulation/adverse effects ; Depression/therapy ; Treatment Outcome ; Antidepressive Agents/therapeutic use
    Chemical Substances Antidepressive Agents
    Language English
    Publishing date 2023-04-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1174775-4
    ISSN 1465-7309 ; 1067-3229
    ISSN (online) 1465-7309
    ISSN 1067-3229
    DOI 10.1097/HRP.0000000000000364
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