Evidence map›Paper›PMID 35775159›Full record

ReviewThe American journal of psychiatry2022

Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation?

Diego A Pizzagalli

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in The American journal of psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07388004 (Rewiring Expectations and Amplifying Rewards), which is not on this map. Cited by 116 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 2 pooled it
18.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07388004 narecruitingnot on this mapstarted 2025, after this paper: background citation

Rewiring Expectations and Amplifying Rewards: A Study Protocol for a Randomized Controlled Trial of Mechanism-Based Group Psychotherapy for Major Depressive Disorder

TypeinterventionalSponsorPhilipps University MarburgRan2025 to 2028Enrolled150ConditionsMajor Depressive Disorder (MDD)ArmsExpectation-Focused Psychotherapeutic Intervention, Reward Enhancement and Activation Therapy
3 · Its place in the literature

Who cites it

116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 169 citations in OpenAlex.

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  9. Efficacy ofWorld journal of psychiatry · 2025
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56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Diego A PizzagalliDepartment of Psychiatry, Harvard Medical School, Boston, and McLean Hospital, Belmont, Mass.
McLean Hospital · US

Funding

Project 4_Bruchas : Circuit-level Approaches for Dissecting Approach/Avoidance Behaviors Mediated by Nociceptin Systems in MiceP50MH119467 · NIMH · MCLEAN HOSPITAL · PI FRANK, MICHAEL J. · 2020 to 2024
$15.9M
Neuroimaging Studies of Reward Processing in DepressionR37MH068376 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI Diego A Pizzagalli · 2016 to 2026
$7.4M
Early Life Stress and Depression: Molecular and Functional Imaging ApproachesR01MH095809 · NIMH · MCLEAN HOSPITAL · PI DU, FEI, PIZZAGALLI, DIEGO A · 2012 to 2024
$6.4M
Sex, Hormones and GABA in Stress Induced Anhedonia in DepressionR01MH108602 · NIMH · MCLEAN HOSPITAL · PI GOLDSTEIN, JILL M, PIZZAGALLI, DIEGO A · 2016 to 2020
$3.2M
NIMH NIH HHS P50 MH119467NIMH NIH HHS R01 MH095809NIMH NIH HHS R01 MH108602NIMH NIH HHS R37 MH068376
6 · The paper itself

Abstract

Anhedonia-the loss of pleasure or lack of reactivity to pleasurable stimuli-remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked to poor disease course, worse response to psychological, pharmacological, and neurostimulation treatments, and increased suicide risk. Moreover, although some neural abnormalities linked to anhedonia normalize after successful treatment, several persist-for example, blunted activation of the ventral striatum to reward-related cues and reduced functional connectivity involving the ventral striatum. Critically, some of these abnormalities have also been identified in unaffected, never-depressed children of parents with major depressive disorder and have been found to prospectively predict the first onset of major depression. Thus, neural abnormalities linked to anhedonia may be promising targets for prevention. Despite increased appreciation of the clinical importance of anhedonia and its underlying neural mechanisms, important gaps remain. In this overview, the author first summarizes the extant knowledge about the pathophysiology of anhedonia, which may provide a road map toward novel treatment and prevention strategies, and then highlights several priorities to facilitate clinically meaningful breakthroughs. These include a need for 1) appropriately controlled clinical trials, especially those embracing an experimental therapeutics approach to probe target engagement; 2) novel preclinical models relevant to anhedonia, with stronger translational value; and 3) clinical scales that incorporate neuroscientific advances in our understanding of anhedonia. The author concludes by highlighting important future directions, emphasizing the need for an integrated, collaborative, cross-species, and multilevel approach to tackling anhedonic phenotypes.

Indexed as

Major Depressive DisorderVentral StriatumAnhedoniaHumansMagnetic Resonance ImagingRewardBrain Imaging TechniquesCognitive NeuroscienceDepressive DisordersMajor Depressive DisorderNeurocircuitry

Identifiers

PMID35775159
PMCPMC9308971
OpenAlexW4283765980

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.