Study identifies plasma markers linked to mental health in young adults

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In psychopathology, the P-factor suggests the presence of a common factor driving various mental health disorders. recent Translational psychiatry The study aims to explore P-factor-related plasma proteins in young adults and provide novel insights into the mental health status of this subpopulation.

Study: Proteomic insights into mental health conditions: plasma markers in young adults.  Image credit: Pavlova Yuliia / Shutterstock.com Study: Proteomic insights into mental health status: plasma markers in young adults. Image credit: Pavlova Yuliia / Shutterstock.com

Background

Mental health problems are often undiagnosed and untreated despite their significant economic costs. There is an urgent need to rapidly identify patients, establish preventive measures, as well as improve treatment and diagnostic methods. Mental health disorders have common underlying causes, which can be psychological, social and biological.

The “common psychopathology factor” or latent P-factor suggests the presence of a common factor driving various mental health disorders. The p-factor is similar to the g-factor of intelligence, which relates to a person’s tendency to do well on various cognitive tests if he does well on a test. Individuals who report a high P-factor find it difficult to control or control when dealing with the environment, others, or themselves.

Biomarker discovery helps researchers understand the biological processes underlying mental health conditions. Interest in plasma proteomics has increased following the development of sophisticated analytical methods and “omics” technologies.

Liquid chromatography-mass spectrometry (LCMS)/MS-based proteomics enables simultaneous quantification and identification of tens of thousands of proteins, accelerating biomarker discovery efforts and reducing the resources required for this process.

About this research

To date, P-factor studies have not been combined with proteomics analysis to identify markers associated with a patient’s overall mental health status. The FinnTwin12 (FT12) cohort, a longitudinal study of twins born between 1983 and 1987 in Finland, was used for the present analysis.

A total of 5,600 twins answered questionnaires in the Finnish Central Population Registry, of whom 1,347 were studied more extensively at age 14, with additional questionnaires and psychological interviews. At age 22, these individuals were reassessed, of whom 779 provided venous blood plasma samples and participated in in-person assessments.

original search

A total of 13 plasma proteins were associated with P-factor scores in young adults. These proteins were present in the human plasma proteome database except Fc gamma binding protein (FCGBP), which was negatively correlated with P-factor.

Ten proteins belonged to a network associated with epidermal growth factor receptor (EGFR), while eight were directly associated with EGFR. This is important, as previous studies have linked EGF-related signaling pathways to synaptic plasticity, fear, and neurodevelopment.

A negative correlation was observed between P-factor and heparan sulfate proteoglycan 2 (HSPG2). HSPG2 acts as a co-receptor for membrane proteins and growth factors. A combination of maternal suppressors against centrosomal protein 350 (CEP350), Decapentaplegic 5 (SMAD5) and HSPG2 has recently been described as a biomarker for major depressive disorder (MDD).

P-factor and fibulin-1 (FBLN1) were negatively correlated. FBLN1 modulates the neurotrophic activities of amyloid precursor protein and is associated with central nervous system (CNS) development. Reduced FBLN1 plasma protein levels have previously been observed in MDD patients.

A non-linear relationship was observed between P-factor and cathepsin B (CTSB), which has been suggested to increase neurotrophin expression and thereby affect brain health. Other proteins directly related to EGFR and associated with P-factor were superoxide dismutase 2 (SOD2), Golgi membrane protein 1 (GOLM1), and uromodulin (UMOD).

Furthermore, an association of P-factor with ficolin 3 (FCN3) and plasma reticulon-4 receptor-like 2 (RTN4L2) was noted. RTN4L2 consists of neuron surface proteins that regulate axonal and dendritic growth. Importantly, further research is needed to elucidate the exact role of RTN4R in driving mental health disorders.

Ficolin was negatively correlated with schizophrenia severity.

Conclusion

Studying plasma proteomic profiles provides a better understanding of the underlying biological processes associated with P-factor. Thus, this approach has the potential to facilitate the development of new diagnostic, screening, and treatment strategies for patients with mental health disorders. Here, proteins were identified with common cellular functions associated with P-factor, reflecting common psychopathology.

In the future, more research is needed to explore the identified proteins and their potential as biomarkers for mental health conditions. The use of the P-factor may aid in the development of interventions targeting common factors among different psychiatric disorders.

Journal Reference:

  • Afonin, AM, Piironen, A., de Sousa Maciel, I., etc. (2024) Proteomic insights into mental health conditions: plasma markers in young adults. Translational psychiatry. 14(1), 1-9. doi:10.1038/s41398-024-02751-z



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