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. 2022 Apr 26;23(9):4754.
doi: 10.3390/ijms23094754.

Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies

Sonja Elsaid  1   2   3 , Dafna S Rubin-Kahana  1   4 , Stefan Kloiber  2   3   4   5   6 , Sidney H Kennedy  2   7   8   9   10 , Sofia Chavez  2   3   4   5 , Bernard Le Foll  1   2   3   4   5   6   11   12   13
Affiliations

Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies

Sonja Elsaid et al. Int J Mol Sci. .

Abstract

(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (1H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using 1H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the 'fear neurocircuitry' in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.

Keywords: Nuclear Magnetic Resonance; Proton Magnetic Resonance Spectroscopy; Social Anxiety Disorder; Social Phobia; neurochemicals; neurometabolites; neurotransmitters; systematic review.

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Conflict of interest statement

Bernard Le Foll has obtained funding from Pfizer (GRAND Awards, including salary support) for investigator-initiated projects. Le Foll has some in-kind donations of cannabis products from Aurora and medication donations from Pfizer and Bioprojet and was provided a coil for the TMS Study from Brainsway. Le Foll has obtained industry funding from Canopy (through research grants handled by CAMH and the University of Toronto), Bioprojet, ACS, and Alkermes. Moreover, Le Foll has received in-kind donations of nabiximols from GW Pharma for past studies funded by CIHR and NIH. He has been consultant for Shionogi and participated in an Advisory Board Meeting for Indivior. Bernard Le Foll is also supported by CAMH by a Clinician-Scientist Award from the Department of Family and Community Medicine at the University of Toronto, and he currently is Addiction Psychiatry Chair at the Department of Psychiatry of the University of Toronto. Furthermore, he is supported by the Waypoint Centre for Mental Health. There are no conflicts of interest related to current work.

Figures

Figure 1
Figure 1
Anatomical structures involved in the ‘fear neurocircuitry’: Coronal view (left), Sagittal view (right). Abbreviations: dmPFC, dorsomedial Prefrontal Cortex; dmACC, dorsomedial Anterior Cingulate Cortex; dlPFC, dorsolateral Prefrontal Cortex; vPFC, ventral Prefrontal Cortex; rACC, rostral Anterior Cingulate Cortex; OFC, Orbitofrontal Cortex; PAG, Periaqueductal Gray; LC, Locus Coeruleus.
Figure 2
Figure 2
Retrieval flowchart indicating how the data were obtained for systematic review. Abbreviations: N, number of publications; MRS, Magnetic Resonance Spectroscopy; SAD, Social Anxiety Disorder; HC, healthy controls; 1H MRS, Proton Magnetic Resonance Spectroscopy.
Figure 3
Figure 3
The Summary of Neurochemical Changes Associated with Social Anxiety Disorder: Mechanisms proposed in the 1H MRS studies (light gray boxes); Reported metabolic changes (white boxes). Abbreviations: NAA, N-acetyl aspartate; tCr, total creatine; tCho, total choline; mI, myo-inositol; GABA, gamma-aminobutyric acid; Glu, glutamate; Gln, glutamine; GAD, glutamic acid decarboxylase; ATP, adenosine triphosphate; CK, creatine kinase; PYC, phosphatidylcholine; PI, phosphoinositol; ASPA, aspartoacylase; DAG; diacylglycerol; IP3, inositol triphosphate.
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