Peripheral immune-metabolic markers and quantitative EEG in drug-naïve first-episode mania: A case-control study

Inflammation is implicated in bipolar disorder and quantitative EEG (QEEG) measures cortical oscillatory activity, but the two have not been examined together in first-episode mania.

Sixty drug-naïve inpatients with a first manic episode (DSM-5) and sixty age- and sex-matched healthy controls were enrolled. Peripheral inflammatory measures, including the monocyte-to-lymphocyte ratio (MLR), C-reactive protein and albumin, were obtained from routine blood tests, and resting eyes-open EEG absolute spectral power was computed across five cortical regions and four bands. Groups were compared with Mann-Whitney U tests with Benjamini-Hochberg correction, and within-patient inflammation-QEEG associations examined by hierarchical regression adjusted for age, education and sex.

Patients had higher monocyte counts (q = 0.004), higher MLR (q = 0.003) and lower albumin (q = 0.045) than controls. Absolute spectral power was higher in patients in 9 of 20 region × band cells, all surviving correction. Within patients, lower albumin was associated with higher frontal (β = -0.42, p = 0.006) and central (β = -0.44, p = 0.003) beta power, persisting after adjustment for smoking and log-transformation. Across all 20 cells with correction, these were the strongest associations but did not survive (minimum q = 0.17).

First-episode drug-naïve mania is accompanied by an immune-metabolic shift and broad cortical oscillatory change. The albumin-beta association is exploratory and hypothesis-generating, and requires replication. Limitations include the single-centre cross-sectional design, modest sample size, and an inflammatory panel restricted to routine measures.