Plasma Proteomic Biomarker Studies in Adolescent Mental Health: Unveiling Potential Predictors of Mental Dysfunction


Plasma proteomic biomarker studies in mental health diseases are a relatively new and promising field of research. Mounting evidence indicates alterations in plasma proteins associated with various mental disorders, including depression (MDD), schizophrenia (SCZ), psychotic disorders, and bipolar disorders.

Shared pathways, such as the complement cascade and interleukin signaling, appear to be commonly affected in these major psychiatric disorders.

In this study, the researchers investigated plasma protein alterations related to immune responses, blood coagulation, complement cascade, neuronal degeneration, and neurogenesis in adolescents at high risk of mental dysfunction, using the self-reported Strengths and Difficulties Questionnaire (SDQ) score as an indicator of mental health predisposition.

However, ethical considerations must be taken into account while assessing the risk of mental health problems in adolescents.


Mental health disorders are complex conditions with multifactorial etiologies. Identifying reliable biomarkers for early detection and understanding the underlying mechanisms of these disorders is critical for timely intervention and personalized treatment strategies. Plasma proteomics, which involves the study of the entire set of proteins in the blood, has emerged as a promising avenue for exploring potential biomarkers associated with mental health diseases.

The Self-Reported Strengths and Difficulties Questionnaire (SDQ) has been widely used as a screening tool for mental health issues in children and adolescents. Previous research has demonstrated its predictive value when combined with other informants, making it a useful and valid tool for identifying those at high risk of mental disorders.


In this study, the researchers focused on adolescents and employed the SDQ score as an indicator of mental health dysfunction and predisposition to mental health issues. We utilized the QLattice symbolic-regression-based algorithm to analyze the potential of plasma proteins to predict the SDQ status.


The researchers observed significant associations between the SDQ score and plasma protein alterations in adolescents. Among the 58 proteins found to be altered, 39 were enhanced, while 19 were reduced in the raised SDQ score group. Notably, several of these proteins had previously been reported as altered in past blood proteomics studies related to mental disorders, confirming their potential as biomarkers.

Pathway Analysis

Blood coagulation and immune responses, including the complement cascade, were identified as the most enriched pathways associated with the SDQ score. These findings were consistent with previous research demonstrating associations between early changes in complement and coagulation cascades and increased risk of psychotic disorders in adolescents. Similar changes in immune responses and blood coagulation have also been reported in patients with schizophrenia, depression, and bipolar disorder.

Predictive Protein Models

the researchers identified eleven proteins with the potential to predict the SDQ status. Four of these proteins had previously reported connections to the central nervous system (CNS), neurogenesis, or mental health. Notably, APLP1, involved in brain development and synaptogenesis, exhibited a significant negative association with the SDQ score. This finding, along with other proteins’ connections to neuronal development and neuroplasticity, opens new avenues for exploring brain development and mental health in adolescents.


One of the main limitations of this study is the relatively low sample size compared to the number of identified proteins. However, statistical power was strengthened through linear modeling and group-based comparisons, enabling the detection of significant alterations. Moreover, non-fasting plasma samples were used due to practical and ethical issues, which may have influenced protein composition and concentrations in the blood.


This study sheds light on the novel field of plasma proteomic biomarker studies in adolescent mental health. The identified plasma protein alterations associated with the SDQ score provide valuable insights into the potential role of immune responses, blood coagulation, and complement cascade in the pathophysiology of mental disorders.

Additionally, the predictive protein models, including proteins with known connections to CNS and neuronal development, offer promising leads for further investigation of brain development and mental health in adolescents.

Though this study has limitations, its findings contribute to the growing body of knowledge on early biomarkers for mental health disorders and may pave the way for future research aimed at improving early detection and intervention strategies.

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