Intrusive Thinking unravels allostatic dysregulation of glutamatergic neurometabolism within Anterior Cingulate Cortex in Generalized Anxiety Disorder

Alterations in glutamatergic and GABAergic neurotransmission are posited to be implicated in the pathophysiology of stress-related disorders. However, in humans existing evidence is inconsistent. Indeed, comparisons between pathological and healthy individuals are primarily at rest and not during specific disease states, making it difficult to understand processes underpinning transdiagnostic psychiatric symptoms. The present study applied 1H magnetic resonance spectroscopy in the anterior cingulate cortex to investigate the effects of an experimental induction of intrusive thinking on glutamate (Glx, glutamate/glutamine ratio) and GABA in pathological worriers and controls (n = 33; 15 males). While increases in GABA were elicited in both groups, indicating enhanced inhibitory effort to suppress intrusive thoughts, an opposite pattern emerged for Glx with an increase in controls and a decrease in worriers. Notably, resting levels of GABA and Glx resulted capable of predicting subjective responses to the induction, namely levels of intrusiveness and repetitiveness. The ecological validity of such prediction was supported by an ecological momentary assessment of intrusive thinking on the same participants. These preliminary findings suggest that glutamatergic dysfunctions may contribute to the maintenance of intrusive thinking in pathological worriers and may inform personally-tailored treatments in the framework of precision psychiatry.