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      Compromised dynamic cerebral autoregulation in patients with generalized anxiety disorder: a study using transfer function analysis

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          Abstract

          Background

          Patients with generalized anxiety disorder (GAD) usually present with various neurological symptoms, but the mechanisms remain unclear. We aimed to analyze the characteristics of dynamic cerebral autoregulation (dCA) in patients with GAD.

          Methods

          Patients (aged ≥18 years) who were diagnosed with GAD were enrolled in this study. Medically and psychiatrically healthy volunteers were recruited as controls. Subjects received the Hamilton Rating Scale for Anxiety (HAMA) and 17-item Hamilton Depression Rating Scale (HAMD) evaluation. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were recorded simultaneously from each subject. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference, gain, and coherence function.

          Results

          A total of 57 patients with GAD and 40 healthy volunteers were enrolled. We found that the phase difference values were significantly compromised in patients with GAD. In the Spearman correlation analysis, the phase difference values were negatively correlated with the HAMA scores and the HAMD scores. In the multiple linear regression analysis, GAD is negatively correlated with the phase difference values, whereas age is positively correlated with the phase difference values.

          Conclusions

          Our results suggested that the dCA was compromised in patients with GAD and negatively correlated with the score of anxiety. Improving the dCA may be a potential therapeutic method for treating the neurological symptoms of GAD patients.

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          Most cited references37

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          Cerebral autoregulation.

          Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.
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            Autonomic characteristics of generalized anxiety disorder and worry.

            Autonomic characteristics of generalized anxiety disorder (GAD) and worry were examined using measures of heart period variability. The cardiorespiratory responses of 34 GAD clients and 32 nonanxious control subjects were recorded during resting baseline, relaxation, and worry periods. Results indicated differences between GAD subjects and controls as well as among baseline, relaxation, and worry periods. GAD clients exhibited shorter cardiac interbeat intervals (IBIs) and lower high frequency spectral power across all task conditions. Relative to baseline and relaxation conditions, worry was associated with (1) shorter IBIs, (2) smaller mean successive differences (MSD) of the cardiac IBIs, and (3) lower high frequency spectral power. These findings suggest that GAD and its cardinal feature (worry), are associated with lower cardiac vagal control. The findings of the present study provide evidence for the utility of further exploration of the role of autonomic nervous system activity in GAD.
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              Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder.

              Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism.
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                Author and article information

                Contributors
                zhen1ni2@163.com
                764616729@qq.com
                jia.liu@siat.ac.cn
                Wangzanprof@163.com
                doctorjinhang@hotmail.com
                ql.qiu@siat.ac.cn
                +86-13596116866 , sjnksunxin@163.com
                +86-13756661217 , doctoryangyi@163.com
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                1 June 2018
                1 June 2018
                2018
                : 18
                : 164
                Affiliations
                [1 ]GRID grid.430605.4, Department of Neurology, , The First Hospital of Jilin University, ; Xinmin Street 71#, Chang Chun, 130021 China
                [2 ]GRID grid.430605.4, Clinical Trail and Research Center for Stroke, Department of Neurology, , The First Hospital of Jilin University, ; Chang Chun, China
                [3 ]ISNI 0000 0001 0483 7922, GRID grid.458489.c, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Xueyuan Avenue, Shenzhen University Town, ; Shenzhen, China
                Author information
                http://orcid.org/0000-0002-9729-8522
                Article
                1713
                10.1186/s12888-018-1713-z
                5984810
                29859053
                819d08b0-0710-4ea6-9252-3518124423f5
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 September 2017
                : 2 May 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81501166
                Award Recipient :
                Funded by: Young Elite Scientists Sponsorship Program by CAST
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Clinical Psychology & Psychiatry
                generalized anxiety disorder,dynamic cerebral autoregulation,transcranial doppler

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