Reduced left dorsolateral prefrontal activation and right inferior frontal de-oxygenation differ between psychotic...

Adolescents with major depressive disorder (MDD) who exhibit psychotic symptoms (MDD-Psy) often show greater clinical severity and higher suicide risk than those without psychosis (MDD-NonPsy). It remains unclear whether prefrontal hemodynamic responses during cognitive challenge can differ between these subgroups.

We recruited 273 adolescents aged 14-16 years (110 MDD-NonPsy, 163 MDD-Psy). All completed a 60-s verbal fluency task (VFT) while 53-channel functional near-infrared spectroscopy recorded oxy- and deoxyhemoglobin (HbO, HbR) from six frontal ROIs. Whole-brain FDR correction identified baseline-deviated channels, and ROC analyses tested the discriminative value of significant channels/ROIs. Clinical severity was indexed by the Kutcher Adolescent Depression Scale (KDAS) and the Brief Psychiatric Rating Scale (BPRS).

Compared with MDD-NonPsy, adolescents with MDD-Psy exhibited higher KDAS (median 16 vs 13; z = -7.07, p < 0.001) and BPRS total scores (median 35 vs 28; z = -11.02, p < 0.001). After FDR correction, MDD-NonPsy showed positive deviations at channels 8 and 23 (t = 2.10-2.70, pFDR=0.038), whereas MDD-Psy exhibited negative deviation at channel 2 (MNI -60, 19, 18; left middle frontal gyrus; t =-2.89, pFDR = 0.004). Across ROIs, only right inferior frontal gyrus HbR differed between groups (median -0.03 vs 0.00 mM·mm; z = -2.18, pFDR = 0.030). No ROI-level HbO differences survived correction. At the single-channel level, HbO at channel 2 and HbR in IFG_R correlated modestly with lower KDAS and restlessness scores (ρ = -0.14 to -0.16, p <0.050). ROC analyses indicated modest but significant classification accuracy for psychosis (AUC = 0.577-0.581, p = 0.030).

Left dorsolateral and right inferior prefrontal hemodynamic signatures differ between adolescents with MDD who present with versus without psychotic features. However, given the absence of healthy control or other psychiatric comparison groups, these findings cannot establish diagnostic specificity. Pending replication in independent samples, these fNIRS-derived hemodynamic signatures may inform future hypothesis-driven research.