Background: Despite the high prevalence of generalized anxiety disorder (GAD) and its negative impact on society, its neurobiology remains obscure. This study characterizes the neurostructural abnormalities associated with key symptoms of GAD, focusing on indicators of impaired emotion regulation (excessive worry, poor concentration, low mindfulness, and physiological arousal).
Methods: These domains were assessed in 19 (16 women) GAD patients and 19 healthy controls matched for age and gender, using questionnaires and a low demand behavioral task performed before and after an induction of perseverative cognition (i.e. worry and rumination). Continuous pulse oximetry was used to measure autonomic physiology (heart rate variability; HRV). Observed cognitive and physiological changes in response to the induction provided quantifiable data on emotional regulatory capacity. Participants underwent structural magnetic resonance imaging; voxel-based morphometry was used to quantify the relationship between gray matter volume and psychological and physiological measures.
Results: Overall, GAD patients had lower gray matter volume than controls within supramarginal, precentral, and postcentral gyrus bilaterally. Across the GAD group, increased right amygdala volume was associated with prolonged reaction times on the tracking task (indicating increased attentional impairment following the induction) and lower scores on the 'Act with awareness' subscale of the Five Facets Mindfulness Questionnaire. Moreover in GAD, medial frontal cortical gray matter volume correlated positively with the 'Non-react mindfulness' facet. Lastly, smaller volumes of bilateral insula, bilateral opercular cortex, right supramarginal and precentral gyri, anterior cingulate and paracingulate cortex predicted the magnitude of autonomic change following the induction (i.e. a greater decrease in HRV).
Conclusions: Results distinguish neural structures associated with impaired capacity for cognitive, attentional and physiological disengagement from worry, suggesting that aberrant competition between these levels of emotional regulation is intrinsic to symptom expression in GAD.
Keywords: ACC, anterior cingulate cortex; Attentional deficit; BDI, Beck Depression Inventory; DLPFC, dorsolateral prefrontal cortex; DMPFC, dorsomedial prefrontal cortex; FFMQ, Five Facets Mindfulness Questionnaire; GAD, generalized anxiety disorder; Generalized anxiety disorder; HC, healthy controls; HRV, heart rate variability; Heart rate variability; IBI, Inter-beat-intervals; ICV, intra-cranial volume; MNI, Montreal Neurological Institute; Magnetic resonance imaging; Mindfulness; PCC, posterior cingulate cortex; PFC, prefrontal cortex; Perseverative cognition; RMSSD, root mean square successive difference; ROI, region-of-interest; RT, reaction times; SCID, Structured Clinical Interview for DSMIV; STAI, State-Trait Anxiety Inventory; VAS, visual-analogue scales; VBM, voxel-based morphometry; mOFC, medial orbitofrontal cortex.