Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients

Abstract

The current inability of psychiatric medicine to objectively select the most appropriate treatment or to predict imminent relapse are major factors contributing to the severity and clinical burden of schizophrenia. We have previously used multiplexed immunoassays to show that schizophrenia patients have a distinctive molecular signature in serum compared with healthy control subjects. In the present study, we used the same approach to measure biomarkers in a population of 77 schizophrenia patients who were followed up over 25 months with four aims: (1) to identify molecules associated with symptom severity in antipsychotic naive and unmedicated patients, (2) to determine biomarker signatures that could predict response over a 6-week treatment period, (3) to identify molecular panels that could predict the time to relapse in a cross-sectional population of patients in remission and (4) to investigate how the biological relapse signature changed throughout the treatment course. This led to identification of molecular signatures that could predict symptom improvement over the first 6 weeks of treatment as well as predict time to relapse in a subset of 18 patients who experienced recurrence of symptoms. This study provides the groundwork for the development of novel objective clinical tests that can help psychiatrists in the clinical management of schizophrenia.

Figure 1

Schematic diagram showing time of sampling of schizophrenia patients treated with antipsychotics. Subjects (n=77) were treated for 6 weeks (T0–T6) with antipsychotics. After this, 0–24 weeks elapsed until the last clinical visit (TR) of the 18 patients who relapsed after an additional 3 weeks to 25 months. Blood samples were drawn from subjects, serum prepared at the indicated time points and the levels of 190 proteins and small molecules were measured by multiplex immunoassay.

Figure 2

Symptom severity measured using PANSS scores during the first 6 weeks of treatment (T0-T6). PANSS positive (top left panel) and negative (bottom left panel) item scores improved significantly over the treatment period. The lines between T0 and T6 connect scores of the same patients. Right panels: the change in positive (top) and negative (bottom) PANSS scores were correlated to the corresponding symptom severity at T0.

Figure 3

Differences of BMI and the levels of leptin, proinsulin and TGF-α between the short- and long-term relapse groups. The measurements were taken at the last clinical visit before relapse (TR).

Figure 4

Differential early response to treatment (between T0 and T6) of leptin, insulin and C-peptide between the short- and long-term relapse groups. The figure shows the difference in the change of levels between T0 and T6 in serum from patients in the two different relapse groups.