fNIRS in differential diagnosis and cognitive correlates of generalized anxiety disorder vs major depressive disorder and comorbidity.

OBJECTIVE

This study aimed to evaluate the diagnostic potential of functional near-infrared spectroscopy (fNIRS) in differentiating patients with major depressive disorder (MDD), generalized anxiety disorder (GAD), and comorbid MDD and GAD (CMG). Additionally, it examined the relationship between task-induced hemodynamic responses during the verbal fluency task (VFT) and cognitive performance across these clinical populations.

METHODS

Using a case-control design, 157 participants were recruited, comprising patients with MDD (n = 49), GAD (n = 33), CMG (n = 35), and healthy controls (HC; n = 40). Data collected included demographic characteristics, clinical rating scales (Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Positive and Negative Syndrome Scale, 32-item Hypomania Checklist), cognitive-behavioral tests [Trail Making Test, Digit Symbol Substitution Test (DSST), and Animal Fluency Test], and fNIRS signals acquired during VFT performance. Intergroup comparisons, ROC analysis and correlation analyses were conducted to assess the diagnostic utility of hemodynamic parameters-specifically, the integral and centroid values-and to explore their associations with cognitive functioning.

RESULTS

In group comparisons, patients with GAD showed significantly different prefrontal integral values (pBonf = 0.003) and bilateral temporal lobe integral values (pBonf = 0.024) compared with the CMG group. Similarly, the GAD group exhibited distinct prefrontal (pBonf = 0.012) and bilateral temporal lobe integral values (pBonf = 0.042) compared with the MDD group. Additionally, a nominal difference in prefrontal integral values was observed between the GAD and HC groups (raw p = 0.046), which did not survive Bonferroni correction. ROC analysis revealed moderate diagnostic value for combined prefrontal-temporal integral values in differentiating GAD from CMG (AUC = 0.76, 95 % CI: 0.64-0.87) and GAD from MDD (AUC = 0.71, 95 % CI: 0.59-0.82), whereas discrimination for GAD versus HC was more limited (AUC = 0.65, 95 % CI: 0.52-0.77). No significant differences were found among the other group comparisons or in other functional indices (p > 0.05). Correlation analyses revealed diagnosis-specific associations between brain activation and cognitive performance. In the GAD group, bilateral temporal lobe integral values were negatively correlated with Animal Fluency Test scores (r = -0.355, p = 0.043). Among participants with CMG, bilateral temporal lobe centroid values were negatively associated with DSST scores (r = -0.338, p = 0.047). In the HC group, prefrontal integral values (r = 0.355, p = 0.024) and bilateral temporal lobe centroid values (r = 0.361, p = 0.022) were positively correlated with DSST scores.

CONCLUSION

fNIRS demonstrates promising potential as a noninvasive tool for distinguishing GAD from CMG and MDD. The observed disorder-specific patterns linking cognitive performance with VFT-induced hemodynamic changes suggest distinct neural mechanisms underlying cognitive dysfunction in MDD, GAD, and their comorbidity.