Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation

Shir Hanuka; Elizabeth A. Olson; Roee Admon; Christian A. Webb; William D.S. Killgore; Scott L. Rauch; Isabelle M. Rosso; Diego A. Pizzagalli

doi:10.1017/s0033291722001106

Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation

Shir Hanuka, Elizabeth A. Olson, Roee Admon, Christian A. Webb, William D.S. Killgore, Scott L. Rauch, Isabelle M. Rosso, Diego A. Pizzagalli

Department of Psychology

Research output: Contribution to journal › Article › peer-review

Abstract

Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined. Methods Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart. Results Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment. Conclusions These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.

Original language	English
Pages (from-to)	4345-4354
Number of pages	10
Journal	Psychological Medicine
Volume	53
Issue number	10
DOIs	https://doi.org/10.1017/s0033291722001106
State	Published - 17 Jul 2023

Bibliographical note

Funding Information:
Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health.

Funding Information:
Over the past 3 years, Dr Pizzagalli has received consulting fees from Albright Stonebridge Group, Neumora Therapeutics (former BlackThorn Therapeutics), Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society for editorial work and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals. In addition, he has received stock options from Neumora Therapeutics (former BlackThorn Therapeutics), Compass Pathways, Engrail Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors report no financial relationships with commercial interest.

Funding Information:
Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health.

Publisher Copyright:
Copyright © The Author(s), 2022. Published by Cambridge University Press.

Keywords

Anhedonia
fMRI
internet-based cognitive-behavioral therapy (iCBT)
major depressive disorder (MDD)
monetary incentive delay (MID)
reward circuit

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1017/s0033291722001106

Cite this

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title = "Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation",

abstract = "Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined. Methods Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart. Results Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment. Conclusions These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.",

keywords = "Anhedonia, fMRI, internet-based cognitive-behavioral therapy (iCBT), major depressive disorder (MDD), monetary incentive delay (MID), reward circuit",

author = "Shir Hanuka and Olson, {Elizabeth A.} and Roee Admon and Webb, {Christian A.} and Killgore, {William D.S.} and Rauch, {Scott L.} and Rosso, {Isabelle M.} and Pizzagalli, {Diego A.}",

note = "Funding Information: Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health. Funding Information: Over the past 3 years, Dr Pizzagalli has received consulting fees from Albright Stonebridge Group, Neumora Therapeutics (former BlackThorn Therapeutics), Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society for editorial work and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals. In addition, he has received stock options from Neumora Therapeutics (former BlackThorn Therapeutics), Compass Pathways, Engrail Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors report no financial relationships with commercial interest. Funding Information: Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health. Publisher Copyright: Copyright {\textcopyright} The Author(s), 2022. Published by Cambridge University Press.",

year = "2023",

month = jul,

day = "17",

doi = "10.1017/s0033291722001106",

language = "English",

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journal = "Psychological Medicine",

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T1 - Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation

AU - Hanuka, Shir

AU - Olson, Elizabeth A.

AU - Admon, Roee

AU - Webb, Christian A.

AU - Killgore, William D.S.

AU - Rauch, Scott L.

AU - Rosso, Isabelle M.

AU - Pizzagalli, Diego A.

N1 - Funding Information: Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health. Funding Information: Over the past 3 years, Dr Pizzagalli has received consulting fees from Albright Stonebridge Group, Neumora Therapeutics (former BlackThorn Therapeutics), Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society for editorial work and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals. In addition, he has received stock options from Neumora Therapeutics (former BlackThorn Therapeutics), Compass Pathways, Engrail Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors report no financial relationships with commercial interest. Funding Information: Research reported in this publication was supported by W81XWH-12-1-0109 from USAMRAA (awarded to S. R., W. D. S. K., and D. A. P.). E. A. O. was partially supported by K23MH112873 from the National Institute of Mental Health (NIMH). R. A. was partially supported by the Israel Science Foundation (ISF) (grant 1738/20) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant ID: 25993). C. A. W. was partially supported by R01 MH116969, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. I. M. R. was partially supported by R01 MH096987 and R01 MH108665 from the NIMH. D. A. P. was partially supported by R37 MH068376 and R01 MH101521 from the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Army, Department of Defense, or the National Institutes of Health. Publisher Copyright: Copyright © The Author(s), 2022. Published by Cambridge University Press.

PY - 2023/7/17

Y1 - 2023/7/17

N2 - Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined. Methods Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart. Results Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment. Conclusions These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.

AB - Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined. Methods Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart. Results Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment. Conclusions These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.

KW - Anhedonia

KW - fMRI

KW - internet-based cognitive-behavioral therapy (iCBT)

KW - major depressive disorder (MDD)

KW - monetary incentive delay (MID)

KW - reward circuit

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Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation

Abstract

Bibliographical note

Keywords

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UN SDGs

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