Association between memory impairment and brain metabolite concentrations in North Korean refugees with posttraumatic stress disorder

<div><p>Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous psychological stress that can result in neurocognitive and neurochemical changes. To date, the causal relationship between them remains unclear. The present study is to investigate the association between neurocognitive characteristics and neural metabolite concentrations in North Korean refugees with PTSD. A total of 53 North Korean refugees with or without PTSD underwent neurocognitive function tests. For neural metabolite scanning, magnetic resonance spectroscopy of the hippocampus and anterior cingulate cortex (ACC) has been conducted. We assessed between-group differences in neurocognitive test scores and metabolite levels. Additionally, a multiple regression analysis was carried out to evaluate the association between neurocognitive function and metabolite levels in patients with PTSD. Memory function, but not other neurocognitive functions, was significantly lower in the PTSD group compared with the non-PTSD group. Hippocampal N-acetylaspartate (NAA) levels were not different between groups; however, NAA levels were significantly lower in the ACC of the PTSD group than the non-PTSD group (t = 2.424, <i>p</i> = 0.019). The multiple regression analysis showed a negative association between hippocampal NAA levels and delayed recall score on the auditory verbal learning test (β = -1.744, <i>p</i> = 0.011) in the non-PTSD group, but not in the PTSD group. We identified specific memory impairment and the role of NAA levels in PTSD. Our findings suggest that hippocampal NAA has a protective role in memory impairment and development of PTSD after exposure to traumatic events.</p></div

Neuropsychological functions of participants.

<p>Neuropsychological functions of participants.</p

Demographic and clinical characteristics of participants.

<p>Demographic and clinical characteristics of participants.</p

Metabolites in the hippocampus and anterior cingulate cortex of participants.

<p>Metabolites in the hippocampus and anterior cingulate cortex of participants.</p

Anatomical location of volumes of interest (VOIs) for magnetic resonance spectroscopy and sample spectra.

<p>A: The left hippocampus. B: The anterior cingulate cortex.</p

Multivariate linear regression models of the associations between metabolite levels and memory function.

<p>Multivariate linear regression models of the associations between metabolite levels and memory function.</p

Data_Sheet_1_Altered Amygdala Resting-State Functional Connectivity and Hemispheric Asymmetry in Patients With Social Anxiety Disorder.docx

<p>Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD). We investigated resting-state functional connectivity (rs-FCN) of the left and right amygdala with various brain regions and functional lateralization in patients with SAD.</p><p>Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala.</p><p>Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044). The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS), and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037).</p><p>Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function plays a central role in the pathophysiology of SAD.</p

¹⁸F-Mefway PET Imaging of Serotonin 1A Receptors in Humans: A Comparison with ¹⁸F-FCWAY

<div><p>Introduction</p><p>The purpose of this research is to evaluate the prospects for the use of 4-(<i>trans</i>-¹⁸F-fluoranylmethyl)-<i>N</i>-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-<i>N</i>-pyridin-2-ylcyclohexane-1-carboxamide (¹⁸F-Mefway) in comparison to ¹⁸F-<i>trans</i>-4-fluoro-<i>N</i>-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-<i>N</i>-(2-pyridyl)cyclohexanecarboxamide (¹⁸F-FCWAY) for the quantification of 5-HT_1A receptors in human subjects.</p><p>Method</p><p>Five healthy male controls were included for two positron emission tomography (PET) studies: ¹⁸F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, ¹⁸F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio).</p><p>Result</p><p>Although the pattern of regional uptakes in the ¹⁸F-Mefway PET was similar to that of the ¹⁸F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in ¹⁸F-Mefway PET was almost half of that in ¹⁸F-FCWAY PET. The skull uptake in ¹⁸F-Mefway PET was only 25% of that in ¹⁸F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for ¹⁸F-Mefway were 17—40% lower than those of ¹⁸F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in ¹⁸F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in ¹⁸F-Mefway PET.</p><p>Conclusion</p><p>As ¹⁸F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, ¹⁸F-Mefway may appear less favorable than ¹⁸F-FCWAY. However, in contrast to ¹⁸F-FCWAY, the resistance to <i>in vivo</i> defluorination of ¹⁸F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, ¹⁸F-Mefway may be a good candidate PET radioligand for 5-HT_1A receptor imaging in human.</p></div

Chemical structures of ¹⁸F-FCWAY and ¹⁸F-Mefway.

<p>Chemical structures of ¹⁸F-FCWAY and ¹⁸F-Mefway.</p

Relationship between the DVR and AUC ratio values for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B). Dashed lines represent identity lines.

<p>Relationship between the DVR and AUC ratio values for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B). Dashed lines represent identity lines.</p