Attenuated interoceptive processing in individuals with major depressive disorder and high repetitive negative thinking
Open accessAbstract
Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD is characterized by altered interoception, which has also been associated with poor outcomes. The present study investigated whether RNT is directly associated with altered interoceptive processing. Interoceptive awareness toward the heart and stomach was probed on the Visceral Interoceptive Attention (VIA) task with fMRI in MDD individuals who were propensity-matched on the severity of depression and anxiety symptoms and relevant demographics but different in RNT intensity (High RNT [H-RNT, n = 48] & Low RNT [L-RNT, n = 49]), and in matched healthy volunteers (HC, n = 27). Both H-RNT and L-RNT MDD individuals revealed reduced stomach interoceptive processing compared to HC in the left medial frontal region and insular cortex (H-RNT: β = -1.04, L-RNT: β = -0.97), perirhinal cortex (H-RNT: β = -0.99, L-RNT: β = -1.03), and caudate nucleus (H-RNT: β = -1.06, L-RNT: β = -0.89). However, H-RNT was associated with decreased right medial temporal lobe activity including the hippocampus and amygdala during stomach interoceptive trials (β = -0.61) compared to L-RNT. Insular interoceptive processing was similar in H-RNT and L-RNT participants (β = -0.07, p = 0.92). MDD individuals with high RNT exhibited altered gastric interoceptive responses in brain areas that are important for associating the information with specific contexts and emotions. Attenuated interoceptive processing may contribute to RNT generation, non-adaptive information processing, action selection, and thus poor treatment outcome.
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Qualitative synthesis found reduced activity in the insular cortex in major depressive disorder across multiple task modalities, with specific reductions in the posterior, dorsal mid- and anterior insula.
“The most consistent finding was reduced activity in the insular cortex in MDD [36–38, 41, 42]. The effect was observed across multiple task modalities, including VIA, heartbeat, and CO2 reactivity, with specific reductions reported in the posterior, dorsal mid- and anterior insula.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [38]
The fMRI Results (page unavailable) report reduced activity in a left medial frontal cluster extending into the insula during stomach-focused VIA trials in MDD participants compared with healthy controls. The Discussion identifies the anterior insula, but reports altered processing of stomach, not heart, signals. This paper does not support reductions across heartbeat and CO2 tasks or specifically in the posterior and dorsal mid-insula. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPark et al. found that individuals with major depressive disorder and high rumination exhibited diminished hippocampal and amygdala activation compared with those with low rumination.
“Park et al. examined rumination subtypes in MDD, finding that individuals with high rumination exhibited diminished hippocampal and amygdala activation compared to those with low rumination [38].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [38]
The Results (fMRI results) report diminished hippocampal and amygdala BOLD signals in the high-RNT group compared with the low-RNT group, but specifically during attention to stomach sensations. The Methods (Participants) describe groups divided by rumination intensity, not rumination subtypes; the citing sentence also omits the task-specific condition of the finding. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAll three whole-brain VIA studies reported decreased caudate nucleus activation in major depressive disorder.
“All three studies reported decreased caudate nucleus activation in MDD.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [38]
The fMRI Results report decreased left caudate nucleus activity in both MDD groups relative to healthy controls during stomach interoceptive processing, but not during heart interoceptive processing. This paper supports the finding for its own whole-brain VIA study; it does not establish that all three studies reported it. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAll three whole-brain VIA studies reported decreased insula activation in major depressive disorder compared with healthy controls.
“Three studies utilized a VIA task to examine interoception in MDD with whole-brain analysis [36–38]. All studies reported decreased insula activation in MDD compared to healthy controls.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [38]
In whole-brain VIA studies, Burrows et al. and Avery et al. identified reduced dorsal mid-insula activation in major depressive disorder, and Park et al. found reduced left insula activation.
“More specifically, Burrows et al. and Avery et al. identified reduced activation in the dorsal mid-insula [36, 37] and Park et al. found reduced activation of the left insula [38].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [38]
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Allostatic Interoceptive Overload Across Psychiatric and Neurological Conditions
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“VIA task : Three studies used variations of the VIA task [ 36 – 38 ].”
Influential
- Authors
- Park, H., Sanchez, S. M., Kuplicki, R., Tsuchiyagaito, A., Khalsa, S. S., Paulus, M. P., & Guinjoan, S. M.
- Affiliations
- University of North Texas (US)
- Laureate Institute for Brain Research (US)
- Corresponding author
- Guinjoan, Salvador M.
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 156
- Pages
- 237-244
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC11008725
- OpenAlex
- W4303983151
- Cited by
- 20
- References
- 62
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 4
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 321 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Psychiatric Research (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- William K. Warren Foundation
- Radiation Research Society
- National Institutes of Health (NCT02450240)
- National Institute of General Medical Sciences (1P20GM121312)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, repetitive negative thinking, interoception, interoceptive awareness, insula, medial temporal lobe, hippocampus, amygdala, perirhinal cortex, caudate nucleus, transdiagnostic symptoms, treatment outcomes
- MeSH terms
- Pessimism, Depressive Disorder, Major, Major Depressive Disorder, Humans
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