Decreased functional connectivity in salience network is associated with symptom severity in betel quid-dependent chewers.

BACKGROUND: Betel quid (BQ) is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have showed that substance-addicted individuals including alcohol, heroin, nicotine and other addictive substance exhibit altered activity patterns of the salience network (SN). However, no study has yet investigated the neural correlates of the resting-state SN and BQ dependence (BQD)-related physiopathological characteristics. METHODS: Thirty-two BQ-dependent (BQD) chewers and 32 healthy controls were recruited to participate in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analysed by independent component analysis (ICA). RESULTS: BQD chewers exhibited decreased functional connectivity in bilateral insula, anterior cingulate cortex (ACC), medial superior frontal gyrus (MSFG) and inferior orbital frontal gyrus (IOFG) [false discovery rate (FDR) correction, p < 0.05]. In the BQD group, the decreased functional connectivity in left ACC correlated negatively with BQDS (BQD Scale) and the duration of BQ. CONCLUSIONS: We reported decreased functional connectivity in resting-state SN of BQD individuals. The decreased functional connectivity in left ACC correlated negatively with BQDS and the duration of BQ. Our findings provided evidence for the importance of the SN in the pathophysiology of BQD and indicated that the SN dysfunction might provide a potential mechanism in BQD development.

Dynamic functional connectivity changes associated with decreased memory performance in betel quid dependence.

The temporal variability of the dynamic functional connectivity (dFC) has been suggested as a useful metric for studying abnormal cognitive function. This study aimed to explore the associations between the temporal properties of dFC and memory performance in betel quid dependence (BQD). Sixty-four BQD individuals and 47 gender- and age-matched healthy controls (HCs) underwent functional magnetic resonance imaging and a series of neuropsychological assessments. The dFC was constructed by calculating the Pearson correlation coefficients within a sliding window and was clustered into three functional connectivity states using k-means clustering. The dFC temporal properties derived from the cluster results were compared between the BQD and HC groups. The results showed that States 1 and 3 featured more frequent and weak connectivity, and State 2 featured less frequent and strong connectivity. There were significant differences for mean dwell time (MDT) in State 3 (p = 0.022) and fraction of time in State 2 (p = 0.018) between the BQD and HC groups. Pearson correlation analyses showed that the MDT in State 1 was negatively correlated with long delay free recall and short delay free recall, and the MDT in State 3 was positively correlated with false positive of long delay recall. Our findings provide strong evidence that MDT match the memory performance and suggest new insights into the pathophysiological mechanism of memory disorders in BQD individuals.

Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network.

Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.

18 F-2-fluoro-2-deoxy-D-glucose-positron emission tomography metabolic pattern assessment in the brain of betel quid dependent individuals.

The primary objective of this study was to identify the metabolic pattern in the brains of betel quid dependent (BQD) individuals using 18 F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (18 F-FDG-PET). A total of 42 individuals (16 BQD individuals and 26 healthy controls, HCs) enrolled at the Department of Nuclear Medicine of Xiangya Hospital underwent brain 18 F-FDG-PET. Group comparisons using statistical parametric mapping (SPM) were performed to identify the 18 F-FDG-PET patterns. Standardized uptake value ratios of anterior cingulate, frontal, thalamus, parietal, occipital, temporal and cerebellum were calculated by SPM. The characteristics of abnormal metabolism in brain regions were quantified using the xjView toolbox, and a 3-D brain map was drawn using BrainNet Viewer. We found significant metabolic reduction in the bilateral middle prefrontal cortex (PFC) and the left orbital frontal gyrus (OFC). In contrast, hypermetabolism was observed in the inferior cerebellum, fusiform, superior cerebellum, parahippocampal, vermis, lingual and thalamus. However, we found no significant difference between the BQD and HC group in the anterior cingulate, thalamus, cerebellum and frontal, temporal, parietal and occipital lobes. In summary, we found abnormal 18 F-FDG-PET metabolic pattern in BQD individuals, and this pattern may help the treatment of BQD.

Betel Quid Dependency and Associated Intrapersonal, Interpersonal, and Environmental Factors among Adolescents: A School-Based Cross-Sectional Survey.

BACKGROUND: Betel quid (BQ) is one of the fourth most commonly used substance globally. Though BQ is a psycho-active substance, yet little has been explored regarding dependency on it particularly among adolescents. OBJECTIVES: Therefore, in this study, we aimed to determine adolescents' dependency on BQ, along with their intrapersonal, interpersonal and environmental determinants of dependency. METHODS: This cross-sectional study focused on 2200 school-going adolescents of Karachi, Pakistan in 2016. Primary outcome was dependency on BQ among adolescents. Both univariate and multivariate regressions were used to estimate crude and adjusted odds ratios (after adjustments for all intrapersonal, interpersonal, and environmental factors) with 95% confidence level. RESULTS: Out of 2200 students, 874 (39.7%) were found to be BQ users amongst whom 69 (7.9%) were dependent on BQ. Comparing the groups with only areca nut users as reference category, betel quid with tobacco additives chewers were considerably dependent (OR = 14.08, 95% CI 3.64-54.16). The individuals who chewed >5 chews per day (OR = 1.87, 95% CI 1.08-3.29) and chronic users (>1year) (OR = 2.02, 95% CI 1.09-3.74) were more likely to be dependent. Older students (>12 years) (OR = 2.12, 95% CI 1.06-4.23), and who studied in government schools were significantly dependent (OR = 3.32, 95% CI 1.80-6.10) than those who studied in private schools. CONCLUSIONS: In conclusion, intrapersonal characteristics like more than 5 chews per day, chronic chewers of more than a year, BQ with tobacco chewers, older adolescents and children studying in government schools were significantly associated with BQ dependency.

Mapping white matter structural and network alterations in betel quid-dependent chewers using high angular resolution diffusion imaging.

Background: To evaluate brain white matter diffusion characteristics and anatomical network alterations in betel quid dependence (BQD) chewers using high angular resolution diffusion imaging (HARDI). Methods: The current study recruited 53 BQD chewers and 37 healthy controls (HC) in two groups. We explored regional diffusion metrics alternations in the BQD group compared with the HC group using automated fiber quantification (AFQ). We further employed the white matter (WM) anatomical network of HARDI to explore connectivity alterations in BQD chewers using graph theory. Results: BQD chewers presented significantly lower FA values in the left and right cingulum cingulate, the left and right thalamic radiation, and the right uncinate. The BQD has a significantly higher RD value in the right uncinate fasciculus than the HC group. At the global WM anatomical network level, global network efficiency (p = 0.008) was poorer and Lp (p = 0.016) was greater in the BQD group. At the nodal WM anatomical network level, nodal efficiency (p < 0.05) was lower in the BQD group. Conclusion: Our findings provide novel morphometric evidence that brain structural changes in BQD are characterized by white matter diffusivity and anatomical network connectivity among regions of the brain, potentially leading to the enhanced reward system and impaired inhibitory control.

Assessment of areca nut use, practice and dependency among people in Guwahati, Assam: a cross-sectional study.

BACKGROUND: Areca nut is the fourth most commonly used psychoactive substance worldwide after tobacco, alcohol and caffeine. In India, it is perceived in various ways, ranging from a 'fruit of divine origin' in Hindu religious ceremonies to a mouth freshener. Areca nut use both on its own and with tobacco additives is addictive. The aim of this study was to understand the pattern of areca nut consumption, to determine the Knowledge, Attitude and Practices (KAP) among areca nut users and the dependency associated with areca nut use. METHODS: A cross sectional study was conducted in Guwahati, Assam using a self-administered questionnaire eliciting the pattern of areca nut consumption, KAP among users and understanding their dependency using Betel Quid Dependence Scale. The chewers of areca nut alone with or without betel quid, gutkha and tobacco participated in the study. Areca nut users were selected using purposive sampling method from the vendor shops of all the four assembly areas of the city. Their participation was voluntary and free not to answer or quit the survey. The data was analysed using SPSS software. RESULTS: A total of 500 participants were approached in all four areas, 479 completed the survey (response rate 95%). The people who participated in the study were mostly male with an average age of 40 years, educated to secondary level or higher, married and self-employed. Betel quid with tamul was the most prevalent form of areca nut chewing in both men and women. About 441 (92%) participants experienced pleasure when chewing areca nut and 327 (68%) chewed it to relieve stress. Only 86 (18%) of subjects had ever tried to quit chewing areca nut and 387 (81%) thought that it was highly addictive. The results revealed relatively high levels of endorsement for 'physical and psychological urgent need' (mean = 43%) and 'increasing dose' (mean = 50%), whereas endorsement level for 'maladaptive use' was low (mean = 16%). CONCLUSION: Areca nut use (tamul) is of major concern in India and many Southeast Asian countries and its use has been increasing across the globe. The evidence suggests a dependence similar to tobacco use and policy makers need to refine its strategy for control of its use by engaging with multiple stakeholders and adapting it to local context with surveillance and cessation guidelines in order to address this issue.

Higher Trait Impulsivity and Altered Frontostriatal Connectivity in Betel-Quid Dependent Individuals.

Objective: Betel quid dependency (BQD) is characterized by functional and structural brain alterations. Trait impulsivity may influence substance dependence by impacting its neurobiological underpinnings in the frontostriatal circuit. However, little is known about the trait impulsivity and its neural correlates in individuals with BQD. Methods: Forty-eight participants with BQD and 22 normal controls (NCs) were recruited and scanned on a 3T MRI scanner. Barratt impulsiveness scale (BIS) was used to measure trait impulsivity: motor, attention, and no plan impulsivity. We used voxel-based morphometry (VBM) to assess the relationship between trait impulsivity and gray matter volumes. The relevant clusters identified were served as regions of interest (ROI) seeds. The whole-volume psycho-physiological interactions (PPI) analysis was used to investigate the changes of functional connectivity related to ROI seeds in the cue-reactivity task condition (BQ and control images). Results: Behaviorally, the BQD group showed significantly higher trait impulsivity including motor and no plan impulsivity than the NCs group. VBM analyses showed that motor impulsivity was negatively associated with gray matter volume of right caudate in the whole sample. No difference in gray matter volume between the two groups was observed. PPI analyses showed that there was a significantly decreased functional connectivity between the right caudate and right dorsolateral prefrontal cortex (DLPFC) when watching BQ related images than control images in individuals with BQD. Furthermore, functional connectivity between the right caudate and right DLPFC was negatively correlated with BQ dependency scores. Conclusions: Our study demonstrated the structural basis of trait impulsivity in the caudate and provided evidence for abnormal interactions within frontostriatal circuitsin individuals with BQD, which may provide insight into the selection of potential novel therapeutic targets for the treatment of BQ dependency.

Betel quid dependence mechanism and potential cessation therapy.

BACKGROUND: Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy. METHODS: We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews. RESULTS: Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut. CONCLUSION: In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials.

Dysfunction of the Prefrontal Cortex in Betel-Quid-Dependent Chewers.

Betel quid is the fourth most popular psychoactive agent worldwide. Imaging studies have found altered brain structure in prefrontal cortex (PFC) in betel-quid dependent (BQD) chewers. However, the brain function in PFC associated with BQ use still remains unclear. The present study aimed to examine brain functional activity in PFC in individuals with BQD. This study recruited 48 participants with BQD and 22 normal controls (NCs). Both BQ-specific cue reactivity and Go/NoGo tasks were administered with functional magnetic resonance imaging (fMRI). Behavioral results showed a deficit in the choice reaction time task in BQD group. The fMRI results of the cue reactivity task suggested that, individuals with BQD exhibited responses in right ventromedial PFC, left posterior cingulate cortex (PCC), left lateral parietal lobe (LPL), left middle temporal gyrus and left visual cortex, when seeing BQ images compared with control images. In the Go/NoGo task, relative to NCs group, individuals with BQD showed higher activity in right dorsolateral PFC, right PCC and bilateral LPL between NoGo and Go trials. Across these two tasks, we consistently found disrupted function in PFC in individuals with BQD, which might lead to impaired craving and response inhibition in BQ addiction. Results of current study might shed light on the neural mechanisms involved in BQ use, which could be used as potential guidelines for diagnosis and treatment of BQ dependence.

Reduced Cortical Thickness in the Right Caudal Middle Frontal Is Associated With Symptom Severity in Betel Quid-Dependent Chewers.

BACKGROUND: Findings from brain structural imaging studies on betel quid dependence have supported relations between betel quid chewing and alterations in gray matter volume and white matter integrity. However, the effect of betel quid chewing on cortical thickness and the link between cortical thickness and symptom severity remains unascertained. METHODS: In this observational study, we compared cortical thickness measures from 24 male betel quid-dependent chewers with 27 male healthy controls. Using FreeSufer, we obtained three-dimensional T1-weighted images that were used to compute the thickness of the cerebral cortex throughout the cortical layer. RESULTS: Compared to healthy controls, betel quid dependent chewers displayed significant decreased cortical thickness in the precuneus, entorhinal, right paracentral, middle temporal, and caudal middle frontal gyri. Betel quid dependence scale scores negatively correlated (r = -0.604; p = 0.002) with reduced cortical thickness in the right caudal middle frontal of betel quid-dependent chewers. CONCLUSION: The findings provide evidence for cortical thickness abnormality in betel dependent chewers and further propose that the severity of betel quid symptoms may be a critical aspect associated with the cortical alterations. The observed alterations may serve as potential mechanisms to explain why BQ chewing behavior is persistent among individuals with betel quid dependence.

Structural and Functional Alterations in Betel-Quid Chewers: A Systematic Review of Neuroimaging Findings.

Background: A number of neuroimaging studies have investigated structural, metabolic, and functional connectivity changes in betel quid (BQ) chewers. We present a systematic review of neuroimaging studies with emphasis on key brain systems affected by BQ chewing to bring a better understanding on the neuro mechanisms involved in BQD. Methods: All BQ neuroimaging studies were identified by searching PubMed, EMBASE, and Google scholar for English articles published until March 2018 using the key words: Betel-quid, resting state, functional MRI, structural MRI, diffusion tensor imaging (DTI), and betel quid dependence basing on the PRISMA criteria. We also sought unpublished studies, and the rest were obtained from reference lists of the retrieved articles. All neuroimaging studies investigating brain structural, and functional alterations related to BQ chewing and BQ dependence were included. Our systematic review registration number is CRD42018092669. Results: A review of 12 studies showed that several systems in the brain of BQ chewers exhibited structural, metabolic, and functional alterations. BQ chewing was associated with alterations in the reward [areas in the midbrain, and prefrontal cortex (PFC)], impulsivity (anterior cingulate cortex, PFC) and cognitive (PFC, the default mode, frontotemporal, frontoparietal, occipital/temporal, occipital/parietal, temporal/limbic networks, hippocampal/hypothalamus, and the cerebellum) systems in the brain. BQ duration and severity of betel quid dependence were associated with majority of alterations in BQ chewers. Conclusion: Betel quid chewing is associated with brain alterations in structure, metabolism and function in the cognitive, reward, and impulsivity circuits which are greatly influenced by duration and severity of betel quid dependence.

Reasons for betel quid chewing amongst dependent and non-dependent betel quid chewing adolescents: a school-based cross-sectional survey.

BACKGROUND: Betel quid (BQ) chewing in children is initiated in their adolescence. It is pivotal to understand adolescents' reasons behind chewing BQ. In this study, we aimed to evaluate the reasons for BQ chewing amongst adolescents using reasons for betel quid chewing scale (RBCS) and their associated dependency on it. METHODS: This is a cross-sectional school based survey. Out of 2200 adolescents from 26 schools of Karachi, 874 BQ chewers were assessed for their reasons of BQ chewing and dependency on it. Regression analyses were employed to report crude and adjusted (after adjusting for all reasons of BQ chewing) effect sizes with 95% confidence interval and P-value was set significant at < 0.05. RESULTS: Students who believed that BQ chewing relaxes them (stimulation construct) were twice as likely to be dependent on BQ (OR = 2.36, 95% CI (1.20-4.65) as compared with others. Participants who thought it eases their decision making (stimulation construct), were sizably more likely to be dependent on BQ (OR = 9.65, 95% CI (4.15-22.43) than those who did not consider ease in decision making important. Adolescents who considered not chewing as rude (social/cultural construct), were thrice more likely to be dependent on BQ (OR = 2.50, 95% CI (1.11-5.63) than others. CONCLUSIONS: Stimulation remained fundamental chewing reason followed by social/cultural trigger amongst adolescents. Any future intervention may get favorable results if it addresses ways to overcome stimulation and social/cultural barriers that are strongly associated with BQ chewing and dependency.

Executive function deficit in betel-quid-dependent chewers: Mediating role of prefrontal cortical thickness.

BACKGROUND: Betel quid is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have suggested betel-quid dependence is accompanied by abnormality in brain structure and function. However, the neural correlates of executive function deficit and prefrontal cortical thickness associated with betel-quid chewing still remain unclear. OBJECTIVE: The present study aimed to examine the relationship between executive function deficit and prefrontal cortical thickness in chronic betel-quid chewers. METHODS: Twenty-three betel-quid-dependent chewers and 26 healthy controls were recruited to participate in this study. Executive function was tested using three tasks. Cortical thickness analysis was analyzed with the FreeSurfer software package. RESULTS: Behavioral results suggested a profound deficit of executive function in betel-quid-dependent chewers. Cortical thickness analysis revealed thinner cortex in the bilateral dorsolateral prefrontal cortex in betel-quid-dependent chewers. Further analysis suggested that cortical thickness of the bilateral dorsolateral prefrontal cortex mediated the correlation of betel-quid chewing and executive function. CONCLUSIONS: These results suggest the important role of executive function and cortical thickness of the dorsolateral prefrontal cortex with betel-quid chewing. Our findings provide evidence that executive function deficit may be mediated by the cortical thickness of the dorsolateral prefrontal cortex. These results could potentially help us develop novel ways to diagnose and prevent betel-quid dependence.

Altered Gray-Matter Volumes Associated With Betel Quid Dependence.

Betel quid (BQ) is one of the most commonly consumed psychoactive substances. It has been suggested to be associated with various health issues, especially oral cancer. Evidence also points to possible decreased cognitive functions after long-term BQ chewing, such as attention and inhibition control. The present study aims to investigate the brain structure basis of BQ chewing in Hunan province of China. Twenty-five BQ chewers and 25 controls were recruited to participate in this study. Voxel-based morphormetry analysis revealed that there were three key regions showing structural differences between BQ chewers and controls, including bilateral dorsolateral prefrontal cortex (DLPFC)/insula, ventral medial prefrontal cortex, and left orbitofrontal cortex. Moreover, the GMV in the DLPFC could potentially predict BQ dependence scores, level of daily BQ chewing, and history of BQ chewing. These results suggested that participants who showed BQ chewing dependence may have deficit in inhibition control and affective decision-making, and the level of deficit was dependent on the level of daily BQ chewing, and history of BQ chewing. Understanding the neurobiology features of BQ chewing would help us develop novel ways to diagnose and prevent BQ dependence.

Disrupted Resting-State Default Mode Network in Betel Quid-Dependent Individuals.

Recent studies have shown that substance dependence (addiction) is accompanied with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and betel quid dependence (BQD)-related physiopathological characteristics still remain unclear. Resting-state functional magnetic resonance imaging images were obtained from 26 BQD individuals and 28 matched healthy control subjects. Group independent component analysis was performed to analyze the resting state images into spatially independent components. Gray matter volume was examined as covariate with voxel-based morphometry to rule out its effect on the functional results. The severity of BQD was assessed by the BQD Scale (BQDS). We observed decreased functional connectivity in anterior part of the DMN including ventral medial prefrontal cortex, orbital MPFC (OMPFC)/anterior cingulate cortex (ACC). Furthermore, the functional connectivity within the OMPFC/ACC in BQD individuals was negatively correlated with BQDS (p = 0.01, r = -0.49). We reported decreased functional connectivity within anterior part of the DMN in BQD individuals, which provides new evidence for the role of the DMN in the pathophysiology of BQD.

White Matter Integrity Deficit Associated with Betel Quid Dependence.

Betel quid (BQ) is a commonly consumed psychoactive substance, which has been regarded as a human carcinogen. Long-term BQ chewing may cause Diagnostic and Statistical Manual of Mental Disorders-IV dependence symptoms, which can lead to decreased cognitive functions, such as attention and inhibition control. Although betel quid dependence (BQD) individuals have been reported with altered brain structure and function, there is little evidence showing white matter microstructure alternation in BQD individuals. The present study aimed to investigate altered white matter microstructure in BQD individuals using diffusion tensor imaging. Tract-based spatial statistics was used to analyze the data. Compared with healthy controls, BQD individuals exhibited higher mean diffusivity (MD) in anterior thalamic radiation (ATR). Further analysis revealed that the ATR in BQD individuals showed less fractional anisotropy (FA) than that in healthy controls. Correlation analysis showed that both the increase of MD and reduction of FA in BQD individuals were associated with severity of BQ dependence. These results suggested that BQD would disrupt the balance between prefrontal cortex and subcortical areas, causing declined inhibition control.

Gray matter abnormalities associated with betel quid dependence: a voxel-based morphometry study.

BACKGROUND: Betel quid dependence (BQD) patients have a cluster of cognitive, behavioral, and physiological symptoms which are associated with structural abnormalities in brain gray matter. However, so far there have neither been brain structural studies investigating the alterations related to BQD, nor studies assessing the brain structural changes with clinical indexes. METHODS: 65 subjects were recruited including 33 'pure' BQD patients and another 32 gender and age matched in the control group. T1 structural voxel-based morphometry (VBM) was performed to investigate the gray matter (GM) volume alterations. In BQD patients, Pearson correlation analysis was performed to investigate the association between GM segmentations and clinical indexes, including BQD scores, illness duration, SAS and SDS. RESULTS: Compared with that of the control group, the VBM of GM in BQD patients exhibited a significant decrease in volume (All P values > 0.05, AlphaSim correction) in the midbrain, right anterior cingulate cortex (rACC), bilateral dorsolateral prefrontal cortex (dlPFC) and right superior temporal gyrus (STG), and also there was an increased volume in right hippocampal and right precuneus. GM volumes of the left DLPFC and right rACC showed negative correlation with the duration of BQD, meanwhile, midbrain volumes were negative correlating with BQD scores (All P values > 0.05). CONCLUSIONS: Our findings suggested that brain structural changes were present in BQD patients, and those may be a neurobiological basis for BQD patients. These findings may provide a new insight into the pathogenesis of BQD. Also, VBM is an effective tool for in vivo investigation of gray matter alterations in patients with BQD.