Backtracing persistent biomarker shifts to the age of onset: A novel procedure applied to men’s and women’s white blood cell counts in post-traumatic stress disorder

Highlights

• Some biomarkers in mental disorders retain shifted levels long time after the onset.

• A backtrace procedure for persistent shifts in cross-sectional data is presented.

• It is demonstrated on leukocyte counts in post-traumatic stress disorder.

• Neutrophil, lymphocyte and eosinophil counts showed the most impressive results.

• The procedure opens new avenues for biomarker research in large epidemiological studies.

Abstract

Background

Traumatic experiences tend to be preserved in altered biomarker profiles. These profiles can be traced back from cross-sectional data regarding the age of exposure. Consequently, the change across developmental stages, e.g. from childhood to adulthood, can also be reconstructed. This study introduces a backtrace procedure that is illustrated using white blood cell (WBC) counts in full / partial post-traumatic stress disorder (PTSD). The procedure was applied separately on men's and women's data to provide a replication of the analysis based on different subsamples.

Methods

The analysis was carried out with data from the CoLaus|PsyCoLaus study (N = 5111, 2370 men and 2741 women, age range 35–88 years). It was restricted to traumatic experiences that occurred until the age of 35, i.e., the lower age limit of the sample. The WBC counts from up to two assessments were standardized, pooled and assigned to the reported age of trauma exposure. This resulted in age series for each marker, whereas the reference values were based on subjects who did not experience any trauma exposure. The backtrace procedure ascertained the peaks and troughs of the age series and determined the best-fitting critical age range surrounding each peak or trough based on the best p-value from simple t-tests.

Results

In CoLaus|PsyCoLaus, 750 participants reported trauma exposure until the age of 35, and 86 (out of 329) men and 187 (out of 421) women thereof were coded with a full or partial PTSD. Full / partial PTSD after trauma exposure in childhood was characterized by increased WBC counts (lymphocytes, eosinophils – in women also neutrophils). This pattern was partly retained during adolescence, in men due to eosinophils counts and in women due to lymphocyte counts. For exposure in young adulthood, the deviations were in the negative direction – in men with decreased basophils, in women with decreased lymphocytes and monocytes.

Conclusions

Summarizing, the backtrace approach revealed WBC profiles in PTSD that were specific to particular developmental age stages. The strongest persistent upregulation of the immune system related to trauma exposure was traceable to childhood / early adolescence both in men and in women. Further research will show which biomarkers are similarly suitable for backtracing as WBC counts. As in PTSD, the backtrace approach could also be applied to identifying persistent biomarker profiles in other mental disorders, as well as autoimmune and other chronic diseases.