Alteration pattern of serum albumin levels in schizophrenia from first episode through remission to relapse: a longitudinal study

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Abstract
Serum albumin, a reverse acute-phase protein, tends to decrease in response to acute clinical conditions. We hypothesized that albumin levels would exhibit state-dependent dynamics, with distinct patterns between acute episodes and remission states in schizophrenia. To test this, we conducted a retrospective longitudinal study to investigate the dynamic serum albumin levels in 148 schizophrenia patients, starting from their first episode through remission and subsequent relapse. A matched general population sample served as the control group. Classification models were developed using albumin levels (Albumin current) and changes (ΔAlbumin1 = Albumin current−Albumin previous remission, and ΔAlbumin2 = Albumin current−Albumin previous acute episode) to distinguish clinical states. Model performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Serum albumin levels were significantly lower during acute episodes (first episode: 45·6, standard deviation (SD) 4·0 g/L; relapse: 44·9, SD 4·0 g/L) compared to remission (48·6, SD 2·9 g/L) and matched controls (48·6, SD 3·4 g/L). Patients in remission showed albumin levels comparable to controls. These findings remained consistent after adjustment for potential confounders using mixed-effects model and in sex-stratified analyses. The classification model incorporating ΔAlbumin1 and ΔAlbumin2 achieved an AUC of 0·88 (95% CI: 0·84, 0·92) in distinguishing acute episodes from remission. These findings highlight serum albumin’s potential as a clinically useful biomarker of illness activity/state and mental stress in schizophrenia, with utility in differentiating between acute and remitted states.

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