Table_1_Impulsivity trait mediates the relationship between white matter integrity of prefrontal–striatal circuits and the severity of dependence in alcoholism.DOCX

BackgroundAlcohol dependence (AD) remains one of the major public health concerns. Impulsivity plays a central role in the transfer from recreational alcohol use to dependence and relapse. White matter dysfunction has been implicated in alcohol addiction behaviors and impulsivity. However, little is known about the role of systematic striatal structural connections underlying the mechanism of impulsive traits in AD.MethodsIn our study, we used seed-based classification by probabilistic tractography with five target masks of striatal circuits to explore the differences in white matter integrity (fractional anisotropy, FA) in AD male patients (N = 51) and healthy controls (N = 27). We mainly explored the correlation between FA of the striatal circuits and impulsive traits (Barratt Impulsiveness Scale, BIS-11), and the mediation role of impulsivity in white matter integrity and the severity of alcohol dependence.ResultsCompared with healthy controls, AD showed much lower FA in the left and right striatum–supplementary motor area (SMA) and left striatum–amygdala. We also found the decreased FA of right striatum-vlPFC was correlated with higher impulsivity. Besides, the relationship between reduced FA of right striatum-vlPFC and severity of dependence could be mediated by impulsivity.ConclusionIn our study, we found disrupted white matter integrity in systematic striatal circuits in AD and the decreased FA of right striatum-vlPFC was correlated with higher impulsivity in AD. Our main findings provide evidence for reduced white matter integrity of systematic striatal circuits and the underlying mechanisms of impulsivity in male AD individuals.</p

Demographics of male patients and male control subjects.

<p>Demographics of male patients and male control subjects.</p

Characteristics of Smoking and Nonsmoking Schizophrenic Patients.

<p><b>Note:</b> PANSS = Positive and Negative Symptom Scale; P = PANSS positive symptom subscale; N = PANSS negative symptom subscale; G = PANSS general psychopathology subscale. AIMS = Abnormal Involuntary Movement Scale (AIMS). BMI = body mass index.</p

Total and index scores on the RBANS for smokers and non-smoker in schizophrenia versus controls.

<p><b>Note:</b> * indicates comparison between smoker and nonsmoker pairs in both schizophrenia and controls. *p<0.05; ** p<0.01.</p

Pairwise comparisons for the RBANS index and total scores.

<p><b>Note:</b> Post hoc pairwise analyses were performed with the Scheffe' test.</p

Combining gray matter volume in the cuneus and the cuneus-prefrontal connectivity may predict early relapse in abstinent alcohol-dependent patients

<div><p>Background</p><p>Developing more effective strategies to prevent relapse remains one of the major challenges of treating substance dependence. Previous studies have identified brain abnormalities in abstinent alcoholics. However, whether these persistent brain deficits in abstinence could predict early relapse to alcohol use has not been well established. This study aimed to identify biomarkers of relapse vulnerability by investigating persistent brain abnormalities in abstinent alcohol-dependent patients.</p><p>Methods</p><p>Brain imaging and impulsive behavior data were collected from 56 abstinent alcohol-dependent male inpatients and 33 age-matched male healthy controls. Voxel-based morphometry was used to investigate the differences of grey matter volume between the groups. The resting-state functional connectivity was examined using brain areas with gray matter deficits as seed regions. A preliminary prospective study design was used to classify patients into abstainers and relapsers after a 62-day average abstinence period.</p><p>Results</p><p>Compared with healthy controls, both relapsers and abstainers exhibited significantly reduced gray matter volume in the cuneus. Functional connectivity analysis revealed that relapsers relative to abstainers demonstrated increased cuneus-centered negative functional connectivity within a network of brain regions which are involved in executive control and salience. Abnormal gray matter volume in the left cuneus and the functional connectivity between the right cuneus and bilateral dorsolateral prefrontal cortex could successfully predict relapse during the 3-month follow-up period.</p><p>Conclusions</p><p>Findings suggest that the abnormal gray matter volume in the cuneus and resting-state cuneus-prefrontal functional connectivity may play an important role in poor treatment outcomes in alcoholics and serve as useful neural markers of relapse vulnerability.</p></div

Correlations between MRI measures and behavioral measures of impulsivity in relapsers.

<p>(A´) The rsFC between the right cuneus and the right ACC showed significant positive correlation with average adjusted pumps in relapsers; (B´) The rsFC between the right cuneus and the left ACC showed significant positive correlation with average adjusted pumps in relapsers. (A-B) Brain maps of representative slices of related areas are also showed in the figure and colored dots represent their locations. Arrows are for illustrating purpose and do not imply directionality. Black dots and black line represent relapsers. Blank circles represent abstainers. Abbreviations: ACC, anterior cingulate cortex.</p

Summary of logistic regression analysis for different MRI measure used as a predictor of early relapse.

<p>Summary of logistic regression analysis for different MRI measure used as a predictor of early relapse.</p

Demographic characteristics of patients with schizophrenia (<i>n</i> = 752) with the rs72393728 polymorphism.

<p>Demographic characteristics of patients with schizophrenia (<i>n</i> = 752) with the rs72393728 polymorphism.</p

Group differences of rsFC existed between the seeds and the cluster location.

<p>(A) Compared with HCs, Relapsers showed significantly increased negative functional connectivity between the right cuneus and the right dlPFC; (B) Compared with HCs, Relapsers showed decreased rsFC between the right dlPFC and the left thalamus, and the left globus pallidus; (C) Compared with HCs, Relapsers showed decreased rsFC between the left thalamus and the left inferior temporal gyrus, and the parahippocampal gyrus. Brain maps of representative slices of ROIs are also showed in the figure and colored dots represent seed locations. Bar graphs display mean rsFC z scores for abstainers, relapsers and HCs and the error bars represent standard deviation. Abbreviations: dlPFC, dorsolateral prefrontal cortex; ITG, inferior temporal gyrus; ParaHip, parahippocampal gyrus; HCs, healthy controls; rsFC, resting-state functional connectivity.</p