ReviewMolecular psychiatry2024
Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder.
Review in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Investigation of habenula volume in mood disorders: A meta-analytic study.Psychological medicine · 2026Pooled it
- The improvement effects and mechanisms of virtual reality training on depression: a systematic review from a neurotransmitter-plasticity dual-pathway perspective.Journal of global health · 2026Pooled it
- Prefrontal-bed nucleus of the stria terminalis physiological and neuropsychological biomarkers predict therapeutic outcomes in depression.Nature communications · 2025Trial
- Single ayahuasca administration mitigates long-term behavioral and neurochemical effects of early-life stress in rats.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Mechanisms of Selective Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: Cortico-Striatal Circuitry, Glutamatergic Dysregulation, and Neuroplastic Constraints.Molecular neurobiology · 2026Review
- The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.Nature communications · 2026Article
- Depression-Related Mechanistic and Translational Evidence forLife (Basel, Switzerland) · 2026Review
- METTL3-dependent m⁶A maturation of miR-140-3p contributes to hippocampal neuronal apoptosis through the OTX2/Wnt/β-catenin axis under chronic stress.Molecular biology reports · 2026Article
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Comparative analysis of multiple chronic unpredictable mild stress paradigms in mice: Behavioural and physiological validity.Neurobiology of stress · 2026Article
- Quantitative monitoring of ketamine's impact on synaptic density usingMolecular psychiatry · 2026Article
- Alterations in serum melatonin, IL-6 and BDNF levels and their clinical correlations in first-episode major depressive disorder.Annals of general psychiatry · 2026Article
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Article
- The Relationship Between Trace Elements and Depression.Nutrients · 2026Review
- From lobotomy to connectomics: a critical review of contemporary psychosurgery.Frontiers in psychiatry · 2026Review
- Multi-omics reveals associations between the microbiota-gut-brain axis and antidepressant effects of vagus nerve stimulation.Neurobiology of stress · 2026Article
- Ascorbic acid enhances antidepressant-like efficacy of esketamine: Hippocampal TARP-γ8-containing AMPA receptors mediate synaptic modulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The serotonin deficit hypothesis explanation for major depressive disorder (MDD) has persisted among clinicians and the general public alike despite insufficient supporting evidence. To combat rising mental health crises and eroding public trust in science and medicine, researchers and clinicians must be able to communicate to patients and the public an updated framework of MDD: one that is (1) accessible to a general audience, (2) accurately integrates current evidence about the efficacy of conventional serotonergic antidepressants with broader and deeper understandings of pathophysiology and treatment, and (3) capable of accommodating new evidence. In this article, we summarize a framework for the pathophysiology and treatment of MDD that is informed by clinical and preclinical research in psychiatry and neuroscience. First, we discuss how MDD can be understood as inflexibility in cognitive and emotional brain circuits that involves a persistent negativity bias. Second, we discuss how effective treatments for MDD enhance mechanisms of neuroplasticity-including via serotonergic interventions-to restore synaptic, network, and behavioral function in ways that facilitate adaptive cognitive and emotional processing. These treatments include typical monoaminergic antidepressants, novel antidepressants like ketamine and psychedelics, and psychotherapy and neuromodulation techniques. At the end of the article, we discuss this framework from the perspective of effective science communication and provide useful language and metaphors for researchers, clinicians, and other professionals discussing MDD with a general or patient audience.
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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.