Nucleus accumbens neurochemistry in human anxiety: A 7 T¹H-MRS study

Abstract

Individual differences in anxiety provide a differential predisposition to develop neuropsychiatric disorders. The neurochemical underpinnings of anxiety remain elusive, particularly in deep structures, such as the nucleus accumbens (NAc) whose involvement in anxiety is being increasingly recognized.We examined the associations between the neurochemical profile of human NAc metabolites involved in neural excitation and inhibition and inter-individual variation in temperamental and situational anxiety. Twenty-seven healthy 20-30 years-old human males were phenotyped with questionnaires for state and trait anxiety (State-Trait Anxiety Inventory, STAI), social anxiety (Liebowitz Social Anxiety Scale), depression (Beck Depression Inventory, BDI) and fatigue (Mental and Physical State Energy and Fatigue Scales, SEF). Using proton magnetic resonance spectroscopy ( 1 H-MRS) at 7 Tesla (7T), we measured metabolite levels for glutamate, glutamine, GABA and taurine in the NAc with. Salivary cortisol was also measured. Strikingly, trait anxiety was negatively associated with NAc taurine content. Perceived situational stress was negatively associated with NAc GABA, while positively with the Glu/GABA ratio. These findings were specific, as no correlation was observed between NAc taurine or GABA and other phenotypic variables examined (i.e., state anxiety, social anxiety, depression, or cortisol), except for a negative correlation between taurine and state physical fatigue. This first 7T study of NAc neurochemistry shows relevant metabolite associations with individual variation in anxiety traits and situational stress and state anxiety measurements. The novel identified association between NAc taurine levels and trait anxiety may pave the way for clinical studies aimed at identifying new treatments for anxiety and related disorders.

Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction

“…Therefore, it may possible that psychological stress, as for instance being in the scanner, serves as a confounding variable, which may affect GABA concentrations differentially in healthy controls and T2D patients. However, recent studies showed that stress decreases GABA concentrations in the prefrontal cortex (Strasser et al, 2019;Hasler, van der Veen, Grillon, Drevets, & Shen, 2010; but see also Houtepen et al, 2017). Therefore, it seems unlikely that our findings are due to processes related to stress.…”

Anxiety and Brain Mitochondria: A Bidirectional Crosstalk

“…In support for this hypothesis, high anxiety in Wistar rats is not only associated with decreased mitochondrial respiratory capacity in the nucleus accumbens, as indicated above, but also with increased capacity in the prefrontal cortex [35], and no changes in the basolateral amygdala [36] or in the ventral tegmental area [38]. The sensitivity of the nucleus accumbens to show anxiety-related differences in brain energy metabolites has also been also confirmed with 1 H-NMR spectroscopy approaches in mice [39] and humans [40].…”

“…Chronic stress promotes anxiety [125] as well as oxidative stress damage [126]. In addition, stress increases brain glutamate levels and shifts the excitatory/inhibitory balance towards increased excitation [40,127,128].…”

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo1H-magnetic resonance spectroscopy study at 14 T

“…Importantly, in our study, we also found that NAc taurine levels were the only ones from the measured metabolites that negatively correlated with passive coping responses in the forced swim test, reinforcing the link between levels of this amino acid and energetically-costly coping responses to adversity. In a recent 7T 1 H-MRS in humans, we have recently found a negative correlation between trait anxiety and NAc taurine content (64). Given the high link between trait anxiety and vulnerability to depression (14, 19), our results support the interest in investigating the causal link between NAc taurine and its potential antidepressant actions.…”