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

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.