In psychopathology, the p factor indicates the existence of common factors driving various mental health disorders.recent translational psychiatry The study aimed to discover plasma proteins associated with p-factor in young people and provide new insights into the mental health of this subgroup.
study: Proteomic insights into mental health conditions: plasma markers in young adults. Image credit: Pavlova Yuliia / Shutterstock.com
Despite the huge economic toll mental health problems take, they often go undiagnosed and untreated. There is an urgent need to identify patients early, deploy preventive measures, and improve therapeutic and diagnostic procedures. Mental health disorders share common underlying factors, which may be psychological, social, and biological.
“General psychopathology factors,” or underlying p-factors, suggest that there are common factors driving various mental health disorders. The p-factor is similar to the g-factor in intelligence and relates to a person’s tendency to perform well on a different cognitive test if they perform well on one test. Individuals who report high p factors often find it difficult to control or regulate in their dealings with the environment, others, or themselves.
The discovery of biomarkers helps researchers understand the biological mechanisms behind mental health conditions. Interest in plasma proteomics has increased with the development of state-of-the-art analytical methods and “omics” technologies.
Liquid chromatography-mass spectrometry (LCMS)/MS-based proteomics helps quantify and detect thousands of proteins simultaneously, accelerating biomarker discovery efforts and reducing the resources required for the process.
About this study
To date, p-factor studies have not been combined with proteomic analyzes to detect markers associated with patients’ overall mental health status. The FinnTwin12 (FT12) cohort, a longitudinal study of twins born in Finland between 1983 and 1987, was used for the current analysis.
A total of 5,600 twins answered the Finnish Central Population Register questionnaire, and 1,347 twins underwent a more extensive study at age 14, including additional questionnaires and psychiatric interviews. At age 22, these individuals were reassessed, and 779 provided a venous plasma sample and participated in an on-site assessment.
A total of 13 plasma proteins were associated with p-factor scores in young adults. These proteins are all present in the human plasma proteome database, with the exception of Fc gamma binding protein (FCGBP), which is inversely correlated with p-factor.
Ten proteins belong to a network related to the epidermal growth factor receptor (EGFR), while eight are directly related to EGFR. This is important because previous studies have linked EGF-related signaling pathways to synaptic plasticity, fear, and neurodevelopment.
An inverse correlation was observed between p-factor and heparan sulfate proteoglycan 2 (HSPG2). HSPG2 contains membrane proteins and acts as a coreceptor for growth factors. The combination of centrosomal protein 350 (CEP350), maternal pentapodialysis 5 (SMAD5), and HSPG2 has recently been described as a biomarker for major depressive disorder (MDD).
The p-factor and fibulin-1 (FBLN1) were also negatively correlated. FBLN1 regulates the neurotrophic activity of amyloid precursor protein and is associated with the development of the central nervous system (CNS). Reduced FBLN1 plasma protein levels have been previously observed in MDD patients.
A non-linear relationship was observed between p-factor and cathepsin B (CTSB), which is thought to enhance neurotrophin expression and thereby influence brain health. Other proteins directly associated with EGFR and related to p-factor include superoxide dismutase 2 (SOD2), Golgi membrane protein 1 (GOLM1), and uromodulin (UMOD).
Additionally, associations of p-factor with ficolin 3 (FCN3) and plasma reticulon-4 receptor-like 2 (RTN4L2) were noted. RTN4L2 contains a surface protein in neurons that regulates axonal and dendritic growth. Importantly, more research is needed to elucidate the exact role of RTN4R in causing mental health disorders.
Ficolin is inversely associated with schizophrenia severity.
Studying plasma proteomic profiles can provide a better understanding of the underlying biological processes associated with p-factor. This approach therefore has the potential to facilitate the development of new diagnostic, screening and treatment strategies for patients with mental health disorders. Here, proteins were identified as having common cellular functions associated with p-factors that reflect general psychopathology.
In the future, more research is needed to explore the identified proteins and their potential as biomarkers of mental health states. The use of p factors can also help in the development of interventions that target factors common in a variety of different mental disorders.
- Afonin, AM, Piironen, A., de Sousa Maciel, I., et al.. (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