Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study
Open accessAbstract
Background The DSM-5 encompasses a wide range of symptoms for Major Depressive Disorder (MDD). Symptoms are commonly added up to sum-scores, and thresholds differentiate between healthy and depressed individuals. The underlying assumption is that all patients diagnosed with MDD have a similar condition, and that sum-scores accurately reflect the severity of this condition. To test this assumption, we examined the number of DSM-5 depression symptom patterns in the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) study.Methods We investigated the number of unique symptom profiles reported by 3703 depressed outpatients at the beginning of the first treatment stage of STAR*D.Results Overall, we identified 1030 unique symptom profiles. Of these profiles, 864 profiles (83.9%) were endorsed by five or fewer subjects, and 501 profiles (48.6%) were endorsed by only one individual. The most common symptom profile exhibited a frequency of only 1.8%. Controlling for overall depression severity did not reduce the amount of observed heterogeneity.Limitations Symptoms were dichotomized to construct symptom profiles. Many subjects enrolled in STAR*D reported medical conditions for which prescribed medications may have affected symptom presentation.Conclusions The substantial symptom variation among individuals who all qualify for one diagnosis calls into question the status of MDD as a specific consistent syndrome and offers a potential explanation for the difficulty in documenting treatment efficacy. We suggest that the analysis of individual symptoms, their patterns, and their causal associations will provide insights that could not be discovered in studies relying on only sum-scores.
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Depression is highly heterogeneous, as shown by mixed symptom phenotypes and mixed treatment effectiveness.
“However, depression is an exceedingly heterogeneous disorder as evidenced by the mixed symptom phenotypes that qualify for the disorder (Fried and Nesse, 2015; Young et al., 2014) and the mixed effectiveness of existing treatments (Biesheuvel-Leliefeld et al., 2015; Cipriani et al., 2018; Piet and Hougaard, 2011; Shea et al., 1992; Vittengl et al., 2007).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Fried and Nesse, 2015
Major depressive disorder is a highly heterogeneous disorder.
“Given that MDD is a highly heterogeneous disorder10, we expect that attention impairments may not always be present for all depressed individuals”
From Paying attention to attention in depression (2019) · cites this paper as [10]
Self-reported appraisals are affected by memory and recall biases in reconstructing past events and may be prone to socially desirable reporting from individuals.
“Lastly, self-reported appraisals are affected by memory and recall biases in reconstructing past events and may be prone to socially desirable reporting from individuals [12,15-17].”
In many individuals with depression, it remains undiagnosed and untreated due to barriers such as social stigma and inaccurate assessment methods.
“Yet, in many individuals with depression, it remains undiagnosed and untreated due to barriers such as social stigma and inaccurate assessment methods [1,3,12,13].”
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- Authors
- Fried, E. I., & Nesse, R. M.
- Affiliations
- KU Leuven (BE)
- Arizona State University (US)
- Corresponding author
- Fried, Eiko I.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 172
- Pages
- 96-102
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC4397113
- OpenAlex
- W2164104699
- Cited by
- 1,043
- References
- 79
- Citations by year
- 2026: 146 · 2025: 138 · 2024: 130 · 2023: 124 · 2022: 95 · 2021: 109 · 2020: 104 · 2019: 74 · 2018: 34 · 2017: 33 · 2016: 34 · 2015: 20
- FWCI
- 40.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01mh90003-26-0-0)
- National Institute of Mental Health (N01 MH090003)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, symptom heterogeneity, depression severity, outpatients
- MeSH terms
- Adult, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Outpatients, Severity of Illness Index, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders
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