Metabolic alterations in generalised anxiety disorder: a review of proton magnetic resonance spectroscopic studies.

Generalised anxiety disorder (GAD) is a common psychiatric illness characterised by selective morpho-functional brain alterations. The breath of neuroimaging studies investigating the neural basis of GAD is extensive; however, its pathophysiology is still largely unknown. Specifically for proton Magnetic Resonance Spectroscopy (¹H MRS) investigations, which have the aim of identifying differences in metabolite levels between conditions in key brain areas, often showed contrasting results. Indeed, there are selected ¹H MRS studies reporting deficits of key metabolites in GAD patients; however, collectively the literature remains mixed with respect to consistency of major findings. In this review, we evaluate published ¹H MRS studies on GAD with the final aim of providing a comprehensive overview of the extent of neurometabolic dysfunctions associated with GAD. Interestingly, the majority of the studies reviewed showed altered metabolite levels in the dorsolateral prefrontal cortex and hippocampus suggesting regional specificity. These results also provide evidence of the utility of ¹H MRS not only for elucidating the pathophysiology of neuropsychiatric diseases, but also for the identification of more beneficial and targeted pharmacological interventions. Additionally, future studies are warranted to overcome methodological differences observed across the studies.