Study identifies plasma markers linked to mental health in young adults

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Jan 28 2024

In psychopathology, the p-factor suggests the presence of a common factor driving various mental health disorders. A recent Translational Psychiatry study aimed to discover p-factor-related plasma proteins in young adults and presented novel insights into the mental health status in this sub-population.

Study: Proteomic insights into mental health status: Plasma markers in young adults. Image Credit: Pavlova Yuliia / Shutterstock.com

Background

Mental health issues are often undiagnosed and untreated despite their significant economic cost. There is an urgent need to identify patients early, deploy preventive measures, as well as improve treatments and diagnostic procedures. Mental health disorders have common underlying factors, which could be psychological, social, and biological. 

The "general 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 in intelligence, which relates to an individual's tendency to perform well in different cognitive tests if he/she does well in one test. Individuals who report a high p-factor often find it difficult to control or regulate when dealing with the environment, others, or themselves.

Biomarker discovery helps researchers understand the biological mechanisms underlying mental health conditions. Interest in plasma proteomics has increased following the development of state-of-the-art analytical methods and "omics" technologies.

Liquid chromatography-mass spectrometry (LCMS)/MS-based proteomics aid in the simultaneous quantification and detection of several thousand proteins, accelerating biomarker discovery efforts and reducing the resources required for this process. 

About this study

To date, p-factor studies have not been combined with proteomics analyses to detect markers associated with the 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 current analysis. 

A total of 5,600 twins responded to the Finnish Central Population Registry questionnaire, 1,347 of whom were more extensively studied at 14 years of age, including additional questionnaires and psychiatric interviews. At the age of 22, these individuals were assessed again, 779 of whom provided venous blood plasma samples and attended in-person assessments.

Key findings

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 the p-factor.

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

A negative association was observed between the p-factor and heparan sulfate proteoglycan 2 (HSPG2). HSPG2 comprises membrane proteins and functions as co-receptors for growth factors. A combination of centrosomal protein 350 (CEP350), Suppressor of Mothers against Decapentaplegic 5 (SMAD5), and HSPG2 was recently described to be a biomarker for major depressive disorder (MDD).

The p-factor and fibulin-1 (FBLN1) were also negatively related. FBLN1 modulates the neurotrophic activities of amyloid precursor proteins and is linked to the development of the central nervous system (CNS). Reduced FBLN1 plasma protein levels have previously been observed in MDD patients.

A non-linear relationship was observed between the p-factor and cathepsin B (CTSB), which has been suggested to augment the expression of neurotrophins and, thereby, influence brain health. Other proteins directly related to EGFR and associated with the p-factor included 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 comprises surface proteins in neurons that regulate axonal and dendrite growth. Importantly, more research is needed to elucidate the exact role of RTN4Rs in driving mental health disorders.

Ficolin was negatively correlated with the severity of schizophrenia.

Conclusions

Studying plasma proteomic profiles provides a better understanding of the underlying biological processes associated with the 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 linked to the p-factor, which reflected the general psychopathology.

In the future, more research is needed to explore the identified proteins and their potential as biomarkers for mental health status. The use of the p-factor could also assist in the development of interventions aimed at factors that are common across a variety of different mental disorders.