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

Abstract

This Section of Epidemiology and Psychiatric Sciences appears in each issue of the Journal to stress the relevance of epidemiology for behavioral neurosciences, reporting the results of studies that explore the use of an epidemiological approach to provide a better understanding of the neural basis of major psychiatric disorders and, in turn, the utilisation of the behavioural neurosciences for promoting innovative epidemiological research.The ultimate aim is to help the translation of most relevant research findings into every-day clinical practice. These contributions are written in house by the journal's editorial team or commissioned by the Section Editor (no more than 1000 words, short unstructured abstract, 4 key-words, one 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. Key words: Generalised anxiety disorder, magnetic resonance spectroscopy, metabolites, neurochemicals.Generalised anxiety disorder (GAD) is a common psychiatric disease characterised by specific physical and psychological symptoms, including persisting worry, irritability and fatigue (DSM5, American Psychiatry Association, 2013;Diwadkar et al. 2017). GAD causes high human suffering, which is poorly understood.With respect to neuroimaging studies, the exploration of putative biomarkers of this disease is still at an early stage (Terlevic et al. 2012). This is true especially for the application of proton Magnetic Resonance Spectroscopy (¹H MRS), which has the unique ability of providing important quantitative biochemical information in localised brain areas (Stanley, 2002). This can lead to identifying possible and more effective pharmacological treatments for GAD.

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review

“…Etkin et al15 have also found evidence of an intra-amygdala abnormality with engagement of a compensatory fronto-parietal executive control network, consistent with cognitive theories of GAD. Interestingly, a recent review reported selective metabolic dysfunctions in regions within the prefrontal-limbic network, including the dorsolateral prefrontal cortex (DLPFC) and hippocampus 16…”

“…With regard to neurochemistry, a number of neurotransmitter systems have been implicated in the neurobiology of GAD 16,26,27. Given the known pharmacological and clinical effects of benzodiazepines, the γ-aminobutyric acid (GABA)/benzodiazepine system has become a focus of research in GAD.…”

Proton Magnetic Resonance Spectroscopy to Detect Correlations between Clinical Symptoms and Brain Metabolite Levels in Patients with Tension-type Headache

“…In patients with anxiety, changes in brain function and structure as well as metabolic abnormalities are known to occur [ 24 , 25 ].In this connection, Harper et al found a correlation between choline concentration and negative mood in patients with chronic pelvic pain syndrome [ 26 ]. Unique advantages of 1 HMRS are the ability to provide important quantitative biochemical information in localized brain areas, and to document brain metabolic activity efficiently in people with mood disorders [ 19 , 25 ]. In addition, an association has been reported between chronic headaches and central nervous system alterations [ 11 ].…”

Magnetic resonance spectroscopy across chronic pain disorders: a systematic review protocol synthesising anatomical and metabolite findings in chronic pain patients

“…The crude resolution of centimetres in MRS compared to millimetres in conventional MRI as well as the added scanning time needed to reliably generate robust spectra (increasing the possibility of subject movement) also limits the precision of this technique in brain research. However, despite these limitations, 1 H-MRS is becoming increasingly clinically relevant [47] and is also contributing to our understanding of diseases such as Parkinson’s disease [48], multiple sclerosis [49], epilepsy [50], depression [51], schizophrenia [52, 53], bipolar disorder [54, 55], and anxiety [56, 57].…”