Disorder- and cognitive demand-specific neurofunctional alterations during social emotional working memory in...

Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers.

This study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm.

No behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load.

The moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory.

These findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.