Study reveals potential biomarkers of adolescent mental health risks

Key takeaways:

• At-risk adolescents showed alterations in proteins involved with immune responses and blood coagulation.
• The results support increasing evidence linking those pathways to mental health issues.

Possible biomarkers of an adolescent’s risk for developing mental health issues include alterations in proteins involved with immune responses, blood coagulation and other pathways, data show.

The findings add to increasing evidence tying early changes in blood coagulation and complement cascades to the development of mental health issues in adolescents, Izaque de Sousa Maciel and colleagues wrote in Nature Mental Health, adding that their results are aligned with the current understanding of those relationships.

Maciel and colleagues analyzed the proteins in blood plasma samples collected from 91 adolescents aged 11 to 16 years. They split the adolescents into two groups based on whether they had a low score (n = 42) or high score (n = 49) on the Strengths and Difficulties Questionnaire (SDQ), which screens for emotional and behavioral problems.

The samples and questionnaires were obtained at approximately the same time in 2016 as part of the Spain-based WALNUTs cohort study.

After the plasma samples were depleted of highly abundant proteins, they were analyzed using liquid chromatography electrospray ionization tandem mass spectrometry. The analysis revealed 58 plasma protein alterations associated with SDQ score, 39 of which were more abundant in adolescents with elevated scores and 19 of which were reduced.

There were 13 significantly (false discovery rate-adjusted P < .05) enriched pathways among the alterations associated with SDQ score. The most enriched pathways were related to blood coagulation and immune responses, including the complement cascade. Other enriched pathways were related to neurogenesis, neuronal degeneration and post-translational protein modification.

Maciel and colleagues also performed a clustering analysis of the differentially abundant proteins, which yielded three groups:

• up- and down-regulated proteins involved in neuron growth, synaptic function, glial cell migration and cholesterol transport;
• upregulated proteins mostly involved in complement and coagulation cascades; and
• three down-regulated proteins involved in the olfactory system and three upregulated proteins involved in protein degradation.

The study’s main limitation was that the sample number was “low in relation to the identified proteins,” the researchers wrote. Another limitation was the study’s use of non-fasting blood plasma samples due to constraints of the original WALNUTs study.

Future studies and follow-up data are needed to validate the potential biomarkers in larger cohorts and confirm their associations with mental disorders, Maciel and colleagues wrote.