Anxiety in healthy humans is associated with orbital frontal chemistry

Grachev, Igor D.; Apkarian, A. Vania

doi:10.1038/sj.mp.4000778

Cited by 78 publications

(53 citation statements)

References 42 publications

(58 reference statements)

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“…Also in other disorders with dysbalanced impulsivity such as in borderline personality disorder, an increase in ACC glutamate levels has been described (Hoerst et al, 2010). In line with our results, glutamate concentrations in the frontal cortex of healthy subjects might depend on anxiety levels as revealed by a study of Grachev and Apkarian (2000). The authors showed that subjects with high levels of anxiety display an increased overall chemical activity in the frontal cortex by 430% compared with subjects with low levels of anxiety.…”

Section: Discussionsupporting

confidence: 79%

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Zwanzger

Zavorotnyy

Gencheva

et al. 2013

Neuropsychopharmacol

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According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate þ glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17) ¼ 149.41; po0.0001; PSS: F(1,17) ¼ 88.03; po0.0001) and heart rate (HR: F(1,17) ¼ 72.79; po0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17) ¼ 15.94; p ¼ 0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11) ¼ 8.68; p ¼ 0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both API max (r ¼ 0.598; p ¼ 0.009) and maximum heart rate (HR max ) during challenge (r ¼ 0.519; p ¼ 0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.

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Section: Discussionsupporting

confidence: 79%

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Zwanzger

Zavorotnyy

Gencheva

et al. 2013

Neuropsychopharmacol

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“…Our correlational results at study endpoint add to an emerging literature relating NAA concentrations to anxiety variables, though the directionality and regional localization of the findings have been inconsistent across studies. In a non-clinical sample, NAA concentrations in the orbital frontal cortices were positively related to a composite measure of state and trait anxiety (55), while in social phobics, NAA/Cr in the ACC was found to be elevated and positively related to symptom severity (32). These divergent findings underscore the need for additional research, using consistent metabolite measures and ROIs, in discrete patient populations.…”

Section: Discussionmentioning

confidence: 73%

Hippocampal N-Acetylaspartate Concentration and Response to Riluzole in Generalized Anxiety Disorder

Mathew

Price

Mao

et al. 2008

Biological Psychiatry

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Background: Previous research has suggested the therapeutic potential of glutamate-modulating agents for severe mood and anxiety disorders, potentially due to enhancement of neuroplasticity. We used proton magnetic resonance spectroscopic imaging ( 1 H MRSI) to examine the acute and chronic effects of the glutamate-release inhibitor riluzole on hippocampal N-acetylaspartate (NAA), a neuronal marker, in patients with generalized anxiety disorder (GAD), and examined the relationship between changes in NAA and clinical outcome.

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“…In our previous studies of different cognitive states (studies of anxiety, 36,37 pain, 38 anxiety and pain 39 ) using in vivo proton magnetic resonance spectroscopy ( 1 H-MRS), we demonstrated a sensitivity of the method for documentation of chemical-perceptual characteristics of the human personality, which can be captured by monitoring the regional changes of neuronal marker N-acetyl aspartate (NAA) in relation to specific cognitive measures. These studies already demonstrated that this approach could become a new method for tracking the long-term brain chemical characteristics of anxiety and pain, and, possibly some other cognitive states.…”

Section: Introductionmentioning

confidence: 99%

“…42,43 Thus, any changes in neuronal density/function and/or synaptic connections in the ACC of normal subjects might affect the SCW interference level (hypothesis to be tested). (2) NAA is a sensitive marker for several other cognitive states (depression (manuscript in preparation), anxiety and pain [36][37][38][39]. (3) This chemical is changed the most in neuropsychiatric disorders with abnormal interference (eg schizophrenia, 44,45 Alzheimer's disease, 46 bipolar disorder, 47 and anxiety disorders [48][49][50] ).…”

Section: Introductionmentioning

confidence: 99%

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

et al. 2001

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The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P Ͻ 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P Ͻ 0.001), and was unrelated to other studied regional NAA, including the left ACC (P Ͻ 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected. Molecular Psychiatry (2001) 6, 529-539.

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Anxiety in healthy humans is associated with orbital frontal chemistry

Abstract: The present study examines relationships between regional brain chemistry (as identified by localized in vivo three-dimensional single-voxel proton magnetic resonance spectroscopy (

Cited by 78 publications

References 42 publications

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Hippocampal N-Acetylaspartate Concentration and Response to Riluzole in Generalized Anxiety Disorder

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

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