Major depressive disorder (MDD) occurs frequently in individuals with schizophrenia, and increased levels of C-reactive protein (CRP) in this population were found to be significantly associated with MDD and nonremission on antidepressant therapy, indicating that adjuvant anti-inflammatory strategies may be particularly useful for these patients, according to a study published in Progress in Neuro-Psychopharmacology and Biological Psychiatry.

High-sensitivity CRP (hs-CRP) is a known biomarker for peripheral inflammation and has also been shown more recently to be a biomarker for neuroinflammation. The current study was designed to assess whether abnormal blood levels of hs-CRP are a valid biomarker for increased MDD and a greater rate of nonremission on antidepressant therapy in patients with schizophrenia and those with unipolar disorders.

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Chronic peripheral inflammation was determined via blood CRP levels (normal CRP level ≤3.0 mg/L and high CRP >3.0 mg/L), and MDD and remission/nonremission were assessed using the Calgary Depression Rating Scale for Schizophrenia (CDSS; MDD defined by a CDSS score ≥6, and remission defined by a CDSS score <6 on antidepressant therapy).

Among the 411 patients included in the study (272 with schizophrenia and 139 with unipolar disorder), 41.6% (n=171) were diagnosed with current MDD (27.2% schizophrenia and 69.8% unipolar disorder). Only 37.8% (28/74) of participants with schizophrenia and MDD were treated with antidepressants, compared with 89.7% (87/97) of participants with unipolar disorder. The nonremission rate on antidepressant therapy was 32.6% (28/86) in patients with schizophrenia and 73.1% (87/119) in unipolar disorder.


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Overall, 40.1% of participants with schizophrenia and 28.1% of those with unipolar disorder had abnormal CRP levels. Abnormal CRP levels were associated with major depression in schizophrenia independent of participant sex, age, functioning, antidepressant treatment, psychotic symptomology, metabolic syndrome, and tobacco smoking (adjusted odds ratio [aOR], 1.872; P =.049). Abnormal CRP levels were also associated with nonremission on antidepressant therapy in schizophrenia independent of participant sex, age, functioning, psychotic symptomology, metabolic syndrome, and tobacco smoking (aOR, 3.328; P =.034). No significant association was shown for CRP level and MDD or remission in participants with unipolar disorder.

Although psychotherapy was not included as a variable in this study, it is unlikely that it played a role in the relationship between peripheral inflammation and depression. The study investigators concluded, “Abnormal CRP is a proxy for peripheral inflammation and was found in the present study to be a biomarker of major depression and non-remission under antidepressant in schizophrenia. Hs-CRP dosage may therefore improve major depression diagnosis in [schizophrenia] subjects and guide clinicians toward anti-inflammatory strategies to improve remission in this specific population.”

Reference

Fond G, Micoulaud-Franchi JA, Faugere M, et al. Abnormal C-reactive protein blood levels as a specific biomarker of major depression and non-remission under antidepressants in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2020;97:109800.