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Evaluation of the amygdala and the anterior cingulate cortex by single voxel proton MR spectroscopy in patients with post-traumatic stress disorder after earthquake
Xiaorui Su1, Weina Wang1, Qiyong Gong1, and Qiang Yue1

1Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University, chengdu, People's Republic of China

Synopsis

In order to explore the changes of metabolites in the amygdala and the anterior cingulate of PTSD after earthquake, MR spectroscopy was applied. MRS showed higher ml and NAA levels in ACC, higher NAA levels in the right amygdala of PTSD group as compared to healthy controls. Besides, both in PTSD and healthy controls, NAA+NAAG levels were higher in the left amygdala than the right. And our results indicate there are some metabolic changes in amygdala and ACC of PTSD subjects. Whether combining depressive disorders, cause of PTSD and types of traumatic causes may have contributed to the inconsistency.

Purpose

Previous studies have shown that metabolic abnormalities in PTSD, but conclusions are not unified. And there were few researches about the PTSD after earthquake. We studied the metabolites in patients and healthy controls without depressive disorders, aiming to evaluate whether or not the neuronal integrity in amygdala and ACC is affected in PTSD after earthquake. Through comparing the left with right amygdala in PTSD group, so do in HC group, we want to know whether metabolites are different of bilateral amygdala.

Method

All participants in this study had suffered from a big earthquake in May 2008 in Wenchuan of China. The diagnosis of PTSD were based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). 1 Then , depression levels were assessed using the 21-item Hamilton Depression Rating Scale (HAMD) , participants with scores ＜20 on HAMD-21 were included. All participants were right-hand individuals who were adults, 18 to 65 years old. Exclusionary criteria for all groups included2: a. other axis I psychiatric diagnosis; b. use of psychotropic medications in past 4 weeks; c. any significant medical or neurological conditions or a history of head injury. At last, sixty-six patients with PTSD (22males, 44 females) and fifty-six healthy controls (17males, 39 females) were involved. Age and sex were matched between two groups (Fig 1) . MRS examination was performed on MAGNETOM Germany 3T MR scanner. The normal size of the voxel of interest (VOI) was 20 × 20 × 20 mm3. The data of metabolites were calculated by LCModel, including creatine(Cr),N-acetylaspartate (NAA), NAA+N-acetylaspartylglutamate(NAAG), choline (Cho), myo-inositol (mI),glutamine and glutamate(Glx). The low-quality MRS data were excluded (Cr SNR<15, FWHM >0.08ppm). First, we compared metabolites of anterior cingulate cortex (ACC) and bilateral amygdala between PTSD and HC. Then, respectively compared the left and right amygdala in PTSD subjects and HC (Fig 2) .

Result

As compared to healthy controls, analysis of the proton MRS showed higher mI levels (P=0.035, 28PTSD VS 15HC) and higher NAA levels (P=0.001，42PTSD VS 29HC) in ACC, higher NAA levels(P=0.042，9PTSD VS 8HC) in the right amygdala of PTSD subjects .When compared the left and right of amygdala, MRS showed significantly higher NAA+NAAG levels in the left amygdala of both group (PTSD:P=0.018, 26left VS 21right;HC:P=0.032，21left VS 13right). (Fig 3) .

Discussion and Conclusion

MRS is a noninvasive method to evaluate the metabolites of brain, and wildly used in mental researches (Fig 4) . There are studies of PTSD focusing on ACC and hippopotamus3, which play crucial roles in the biological response to stress, having found metabolic abnormalities. Byung-Joo Ham4 and Norbert Schuffa5 have found decreased NAA levels in anterior cingulate of PTSD. But in our study, on the one hand, we found that increased NAA levels in ACC of PTSD contrasted to healthy controls (Fig 5) . NAA is a putative marker of neuronal integrity, expected to be sensitivity to the detection of neuronal alterations in PTSD. We suspect that the traumatic-course of PTSD may contribute to it. All subjects were scanned after earthquake just several months, longest to one year. Actively stress mechanism of traumatic may consist in neuronal cells, which lead to the increase of NAA. On the other hand, mI levels were higher in ACC and R-amygdala of PTSD. Glial cells contain a high concentration of myo-Inositol, decreased levels have been reported in ACC of major depressive disorder.6-7The increase of mI indicates proliferation of glial cells in PTSD, more actively than healthy controls. Whether combing the depressive orders may have influence on the increase of mI. Davis M’s experiments have shown the amygdala performs a mediating role in the fear-conditioning response.8-9 Few studies have reported the metabolic changes of the amygdala in PTSD. Our results provide the evidence that the amygdala take part in physiopathologic mechanism of PTSD. We also found the left amygdala has higher NAA+NAAG levels than the right both in PTSD and healthy controls. As for it, Jayasundar R10 had a conclusion that almost all the regions in the brain were known to exhibit both structural and functional asymmetries in right-handed subjects. All subjects were right-handed, and our results certified the asymmetries of bilateral brain regions. And G. Castellano et al. 11 had shown the concentration of NAAG increased with the visual stimulus. NAAG would release more responding to the traumatic, then higher NAA levels-plus in our study, NAA+NAAG levels became higher. In a short, the earthquake produces a significant neurochemistry difference in anterior cingulate cortex and the amygdala of PTSD subjects compared to healthy controls.

Acknowledgements

No acknowledgement found.

References

1. Amerikan Psikiyatri Birligi: Mental Bozukluklarin Tanisal ve Sayimsal El Kitabi,4. baski (DSM IV), Amerikan Psikiyatri Birligi, Washington DC, 1994. Köroglu E, çeviri ed. Hekimler Yayin Birligi, Ankara, 1994; 179-194.

2. ZhiYong Yang, Hong Quan, ZuLai Peng, et al. Proton magnetic resonance spectroscopy revealed differences in the glutamate + glutamine/creatine ratio of the anterior cingulate cortex between healthy and pediatric post-traumatic stress disorder patients diagnosed after 2008 Wenchuan earthquake. Psychiatry and

3. Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research – Past, present, and future. Biol. Psychiatry .2006; 60: 376–382. Clinical Neurosciences .2015; 69: 782–790.

4. Byung-Joo Ham, Jeanyung Chey, Sujung J. Yoon,et al. Decreased N-acetyl-aspartate levels in anterior cingulate and hippocampus in subjects with post-traumatic stress disorder: a proton magnetic resonance spectroscopy study. European Journal of Neuroscience. 2007,25: 324–329.

5. Norbert Schuffa, Thomas C. Neylanb, Sabrina Fox-Bosettia,et,al. Psychiatry Research:Neuroimaging. 2008, 162:147–157.

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8. Davis M. The role of the amygdala in fear and anxiety. Annu Rev Neurosci.1992,15:353-375.

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11. G. Castellano, C.S.B. Dias, B. Foerster, et al. NAA and NAAG variation in neuronal activation during visual stimulation. Brazilian Journal of Medical and Biological Research.2012,45: 1031-1036.


Figures

Fig 1 The clinical and demographic data in PTSD subjects and healthy controls, if the data obeys normal distribution, it will be presented as mean ± SD, otherwise as Median(Q1,Q3). Q1:25% of the data ;Q3:75% of the data. For the Cr signalnoiseratio (SNR) in the ACC and bilateral amygdala, it should be greater than or equal to 15 .Every metabolic data is screen by fitting error, it will be excluded if less than 15%.

Fig 2 The brief procedure of collecting and analyzing data is presented above. Subjects involved in PTSD and healthy controls are adults and don’t combine depressive disorders. All participants are right-hand. Age and sex are matched between two groups.

Fig 3 The main results in our study. It shows higher ml and NAA levels in the anterior cingulatecortex, higher NAA levels in the right amygdala of PTSD group as compared to healthy controls. Besides, both in PTSD and healthy controls, NAA+NAAG levels were higher in the left amygdala than the right.

Fig 4 There is a example that metabolic results of LCmodel and locations of interest (ROI) in different directions.

Fig 5 It’s a box plot of NAA in the anterior cingulate cortex when PTSD groups are compared with healthy controls.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)
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