Decreased Thalamocortical Connectivity in Chronic Ketamine Users

Liao, Yanhui; Tang, Jinsong; Liu, Jianbin; Xie, An; Yang, Mei; Johnson, Maritza; Wang, Xuyi; Deng, Qijian; Chen, Hongxian; Xiang, Xiaojun; Liu, Tieqiao; Chen, Xiaogang; Song, Ming; Hao, Wei

doi:10.1371/journal.pone.0167381

Cited by 30 publications

(19 citation statements)

References 40 publications

(46 reference statements)

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“…For instance, cigarette smokers showed reduced connectivity between the thalamus and the dorsolateral PFC, and the strength of the dorsolateral PFC–thalamus connectivity was negatively associated with severity of nicotine dependence (Wang et al, ). Similar results were also shown in ketamine‐dependent individuals (Liao et al, ). In addition, thalamocortical neurons are essential for thalamocortical information transfer and regulation of arousal and sleep (Del Felice, Formaggio, Storti, Fiaschi, & Manganotti, ; Krone et al, ).…”

Section: Introductionsupporting

confidence: 85%

“…Previous neuroimaging studies observed structural and functional differences of thalamus between substance use disorder and healthy controls (Feil, Sheppard, Fitzgerald, Yücel, & Lubman, ). Several studies showed that reduced thalamic connectivity was associated with increased craving and other measures of severity of drug dependence (Liao et al, ; Wang et al, ). However, the implication of thalamocortical circuits in neural mechanisms of AD patients remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Reduced resting‐state functional connectivity and sleep impairment in abstinent male alcohol‐dependent patients

Liu

Cai

Zhao

et al. 2019

Human Brain Mapping

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Alcohol dependence is associated with poor sleep quality, which has both been implicated with thalamocortical circuits function. To identify the possible roles of these circuits in the alcohol‐sleep association, we investigated the volume of both left and right thalamus and corresponding resting‐state functional connectivity (RSFC) differences between 15 alcohol‐dependent patients (AD) and 15 healthy controls (HC) male participants. The neuroimaging findings were then correlated with clinical variables, that is, Alcohol Use Disorders Identification Test (AUDIT) and Pittsburgh Sleep Quality Index (PSQI). Additionally, mediation analysis was carried out to test whether the thalamocortical RSFC mediates the relationship between drinking behavior and sleep impairments in AD when applicable. We observed a significant positive correlation between AUDIT score and PSQI score in AD. Compared with HC, AD showed reduced RSFC between the left thalamus and medial prefrontal cortex (mPFC), orbitofrontal cortex, anterior cingulate cortex (ACC), and right caudate. We also observed a negative correlation between RSFC of the left thalamus–mPFC and PSQI score in AD. More importantly, the left thalamus–mPFC RSFC strength mediated the relationship between AUDIT score and PSQI score in AD. No significant difference was detected in the normalized volume of both left and right thalamus, and volumes were not significantly correlated with clinical variables. Our results demonstrate that AD show abnormal interactions within thalamocortical circuits in association with drinking behaviors and sleep impairments. It is hoped that our study focusing on thalamocortical circuits could provide new information on potential novel therapeutic targets for treatment of sleep impairment in alcohol‐dependent patients.

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Section: Introductionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Reduced resting‐state functional connectivity and sleep impairment in abstinent male alcohol‐dependent patients

Liu

Cai

Zhao

et al. 2019

Human Brain Mapping

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“…On the other hand, few studies have examined changes in cerebral structure, activation and connectivity in chronic ketamine users (Hoflich et al, 2016; Liao et al, 2016; Wang et al, 2013), who frequently suffer comorbid depression (Chang et al, 2016). Women are more vulnerable than men to depression (Kessler, 2003).…”

Section: Introductionmentioning

confidence: 99%

Depression in chronic ketamine users: Sex differences and neural bases

Zhang

Hung³

et al. 2017

Psychiatry Research: Neuroimaging

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Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users.

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“…Serious lower urinary tracts symptoms (increased urinary frequency, urgency, incontinence, hematuria, and dysuria) [14][15][16], gastritis and liver and kidney dysfunction [16,17] are also common in this population. Psychiatric disorders are often comorbid by ketamine include depression, which is remarkably prevalent among chronic ketamine users [18,19] [29]. However, it is still not clear if chronic ketamine intake is the cause or consequence of these brain alterations due to the cross-sectional design of these studies [28].…”

mentioning

confidence: 99%

“…A few neuroimaging studies revealed structural and/or functional abnormalities in the frontal regions in chronic users. For example, compared to controls ketamine users had less bilateral prefrontal grey matter [25], lower white matter integrity and more axon damage in the prefrontal regions [26,27], altered regional synchrony of metabolism in the precentral frontal gyrus and anterior cingulate cortex (ACC) [28] and altered resting state functional connectivity (RSFC) between thalamic nucleus and several cortical regions including the prefrontal area [29]. However, it is still not clear if chronic ketamine intake is the cause or consequence of these brain alterations due to the cross-sectional design of these studies [28].…”

mentioning

confidence: 99%

Ketamine Addiction

Liang¹,

Ungvári²,

Lee³

et al. 2018

Dual Diagn Open Acc

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EditorialKetamine was developed in 1962 as an anaesthetic agent [1] for use in pediatrics, oncology, and veterinary practice [2]. Ketamine primarily and non-competitively antagonizes NMDA (N-methyl-D-aspartate) receptors, thereby interfering with the excitatory amino acid transmission, which underlines its analgesic and dissociative effects [2]. Ketamine also has weak effects on opioid, muscarinic and monoamine receptors [1], enhances the neurotransmission of noradrenaline, serotonin and dopamine in a dose-dependent fashion, which, together with its effects on glutaminergic system, accounts for its psychotomimetic and sympathomimetic effects [2] and addiction potential [3].During the past decade, ketamine has been proven efficacious in treatment-resistant depression [4]. Due to its unique neurochemical profile, ketamine, and its analogue phencyclidine, has also been tried as a new treatments for psychosis [5] and addiction [6,7]. In contrast to increasing research efforts to understand ketamine's potential as a therapeutic agent, only a few studies focused on understanding ketamine addiction.Ketamine misuse started in the United States in the 1970s, soon after its development and wider availability [2]. Ketamine is still a commonly abused drug around the world [8], particularly in East Asia [9]. Ketamine is the second and third most commonly abused drug in Hong Kong [10] and in mainland China and Taiwan [9], respectively. Ketamine is predominantly consumed by young people [10,11], gay clubbers [12,13] and poly-substance users [8].Heavy ketamine users suffer from both physical and mental problems. Serious lower urinary tracts symptoms (increased urinary frequency, urgency, incontinence, hematuria, and dysuria) [14][15][16], gastritis and liver and kidney dysfunction [16,17] are also common in this population. Psychiatric disorders are often comorbid by ketamine include depression, which is remarkably prevalent among chronic ketamine users [18,19] [29]. However, it is still not clear if chronic ketamine intake is the cause or consequence of these brain alterations due to the cross-sectional design of these studies [28].Further, white matter microstructural abnormalities were found predominantly in left prefrontal region in ketamine chronic users when [27], restricted to the right hemisphere white matter regions when compared with poly-drug users [26]. While a significant correlation between the subgenual ACCdorsal medial prefrontal cortex connectivity and depression score was found in female ketamine users but not in female controls, it is hard to draw a conclusion whether it was ketamine use or depression that accounted for the discrepancy between ketamine users and controls [30].To date, there has been no established treatment for ketamine addiction. Abstinence seems to be the essential step for treating physical symptoms induced by ketamine [31] and probably depressive symptoms as well as cognitive impairments [20]. Lamotrigine, a glutamate release inhibitor showed promising effect in reducing ketamine craving ...

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Decreased Thalamocortical Connectivity in Chronic Ketamine Users

Cited by 30 publications

References 40 publications

Reduced resting‐state functional connectivity and sleep impairment in abstinent male alcohol‐dependent patients

Reduced resting‐state functional connectivity and sleep impairment in abstinent male alcohol‐dependent patients

Depression in chronic ketamine users: Sex differences and neural bases

Ketamine Addiction

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