Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation

Jennifer L. Stewart, Evan J. White, Rayus Kuplicki, Elisabeth Akeman, Jerzy Bodurka, Yoon Hee Cha, Justin S. Feinstein, Sahib S. Khalsa, Jonathan A. Savitz, Teresa A. Victor, Martin P. Paulus, Robin L. Aupperle

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized. Methods: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal. Results: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker. Limitations: This was a cross-sectional analysis restricted to women. Conclusions: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalJournal of Affective Disorders
StatePublished - 1 Aug 2020
Externally publishedYes


  • Anxious apprehension
  • Anxious arousal
  • Frontal brain asymmetry
  • Functional magnetic resonance imaging
  • Major depressive disorder


Dive into the research topics of 'Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation'. Together they form a unique fingerprint.

Cite this