Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology

doi:10.1038/s44220-023-00057-5

. 2023 May;1(5):304-315.

doi: 10.1038/s44220-023-00057-5. Epub 2023 May 10.

Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology

Affiliations

¹ Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
² Department of Psychological Science, University of California, Irvine, CA, USA.
³ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴ Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
⁵ Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin, TX, USA.
⁶ HEI-LAB, Lusófona University, Lisbon, Portugal.
⁷ Department of Psychology, University of Winchester, Winchester, UK.
⁸ Department of Psychology, University of Maryland, College Park, MD, USA.

PMID: 37251494
PMCID: PMC10210256
DOI: 10.1038/s44220-023-00057-5

Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology

Jeggan Tiego et al. Nat Ment Health. 2023 May.

. 2023 May;1(5):304-315.

doi: 10.1038/s44220-023-00057-5. Epub 2023 May 10.

Affiliations

¹ Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
² Department of Psychological Science, University of California, Irvine, CA, USA.
³ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴ Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
⁵ Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin, TX, USA.
⁶ HEI-LAB, Lusófona University, Lisbon, Portugal.
⁷ Department of Psychology, University of Winchester, Winchester, UK.
⁸ Department of Psychology, University of Maryland, College Park, MD, USA.

PMID: 37251494
PMCID: PMC10210256
DOI: 10.1038/s44220-023-00057-5

Abstract

Our capacity to measure diverse aspects of human biology has developed rapidly in the past decades, but the rate at which these techniques have generated insights into the biological correlates of psychopathology has lagged far behind. The slow progress is partly due to the poor sensitivity, specificity and replicability of many findings in the literature, which have in turn been attributed to small effect sizes, small sample sizes and inadequate statistical power. A commonly proposed solution is to focus on large, consortia-sized samples. Yet it is abundantly clear that increasing sample sizes will have a limited impact unless a more fundamental issue is addressed: the precision with which target behavioral phenotypes are measured. Here, we discuss challenges, outline several ways forward and provide worked examples to demonstrate key problems and potential solutions. A precision phenotyping approach can enhance the discovery and replicability of associations between biology and psychopathology.

PubMed Disclaimer

Figures

**Fig. 1 |. The HiTOP model.**
The broadest dimensions, reflecting common liabilities to psychopathology, are situated at the top of the hierarchy with the narrowest traits and symptom components situated at the bottom, reflecting liabilities to specific problems. Gray boxes with broken lines indicate hypothesized, but not yet confirmed, constructs. The broken single-headed arrows pointing to ‘Mania’ reflect preliminary relationships awaiting further confirmatory evidence.

**Fig. 2 |. The reflective latent variable model.**
Reflective latent variable (common factor) model in which the unobserved psychobiological attribute (factor or latent construct; ξ), is conceptualized as explaining the variance/covariance in the measured variables (x_1,1–x_1,4) via their factor loadings (λx_1,1–λx_1,4), which are linear regression coefficients. The indicator error variances (also residual variances or uniquenesses; θε_1,1−θε_1,4) capture the variance in each measured variable not explained by the factor (that is, variance not shared with the other indicator variables).

**Fig. 3 |. Precision psychiatric phenotyping.**
Example workflow for a precision psychiatric phenotyping approach in the context of a biology–psychopathology association study.

See this image and copyright information in PMC

Cited by

Multivariate brain-behaviour associations in psychiatric disorders.
Vieira S, Bolton TAW, Schöttner M, Baecker L, Marquand A, Mechelli A, Hagmann P. Vieira S, et al. Transl Psychiatry. 2024 Jun 1;14(1):231. doi: 10.1038/s41398-024-02954-4. Transl Psychiatry. 2024. PMID: 38824172 Free PMC article. Review.
Do We Need a Novel Framework for Classifying Psychopathology? A Discussion Paper.
Rief W, Hofmann SG, Berg M, Forbes MK, Pizzagalli DA, Zimmermann J, Fried E, Reed GM. Rief W, et al. Clin Psychol Eur. 2023 Dec 22;5(4):e11699. doi: 10.32872/cpe.11699. eCollection 2023 Dec. Clin Psychol Eur. 2023. PMID: 38357431 Free PMC article. Review.
Mindfulness Intervention Improves Coping and Perceptions of Children's Behavior among Families with Elevated Risk.
Krause JT, Brown SM. Krause JT, et al. Int J Environ Res Public Health. 2023 Nov 21;20(23):7092. doi: 10.3390/ijerph20237092. Int J Environ Res Public Health. 2023. PMID: 38063522 Free PMC article.
Reexamining developmental continuity and discontinuity in the 21st century: Better aligning behaviors, functions, and mechanisms.
Petersen IT. Petersen IT. Dev Psychol. 2023 Oct 19:10.1037/dev0001657. doi: 10.1037/dev0001657. Online ahead of print. Dev Psychol. 2023. PMID: 37856415
Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders.
Segal A, Parkes L, Aquino K, Kia SM, Wolfers T, Franke B, Hoogman M, Beckmann CF, Westlye LT, Andreassen OA, Zalesky A, Harrison BJ, Davey CG, Soriano-Mas C, Cardoner N, Tiego J, Yücel M, Braganza L, Suo C, Berk M, Cotton S, Bellgrove MA, Marquand AF, Fornito A. Segal A, et al. Nat Neurosci. 2023 Sep;26(9):1613-1629. doi: 10.1038/s41593-023-01404-6. Epub 2023 Aug 14. Nat Neurosci. 2023. PMID: 37580620 Free PMC article.

See all "Cited by" articles

References

1. Perkins ER, Latzman RD & Patrick CJ Interfacing neural constructs with the Hierarchical Taxonomy of Psychopathology: ‘why’ and ‘how’. Personal. Ment. Health 14, 106–122 (2020). - PubMed
1. Insel T et al. Research Domain Criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751 (2010). - PubMed
1. Hyman SE Can neuroscience be integrated into the DSM-V? Nat. Rev. Neurosci 8, 725–732 (2007). - PubMed
1. Singh I & Rose N Biomarkers in psychiatry. Nature 460, 202–207 (2009). - PubMed
1. First MB et al. Clinical applications of neuroimaging in psychiatric disorders. Am. J. Psychiatry 175, 915–916 (2018). - PMC - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources
- Europe PubMed Central
- PubMed Central
Miscellaneous
- NCI CPTAC Assay Portal

[1] Perkins ER, Latzman RD & Patrick CJ Interfacing neural constructs with the Hierarchical Taxonomy of Psychopathology: ‘why’ and ‘how’. Personal. Ment. Health 14, 106–122 (2020). - PubMed

[2] Perkins ER, Latzman RD & Patrick CJ Interfacing neural constructs with the Hierarchical Taxonomy of Psychopathology: ‘why’ and ‘how’. Personal. Ment. Health 14, 106–122 (2020). - PubMed

[3] Insel T et al. Research Domain Criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751 (2010). - PubMed

[4] Insel T et al. Research Domain Criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751 (2010). - PubMed

[5] Hyman SE Can neuroscience be integrated into the DSM-V? Nat. Rev. Neurosci 8, 725–732 (2007). - PubMed

[6] Hyman SE Can neuroscience be integrated into the DSM-V? Nat. Rev. Neurosci 8, 725–732 (2007). - PubMed

[7] Singh I & Rose N Biomarkers in psychiatry. Nature 460, 202–207 (2009). - PubMed

[8] Singh I & Rose N Biomarkers in psychiatry. Nature 460, 202–207 (2009). - PubMed

[9] First MB et al. Clinical applications of neuroimaging in psychiatric disorders. Am. J. Psychiatry 175, 915–916 (2018). - PMC - PubMed

[10] First MB et al. Clinical applications of neuroimaging in psychiatric disorders. Am. J. Psychiatry 175, 915–916 (2018). - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology

Affiliations

Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous