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Open accessJournal ArticleDOI: 10.1038/S41398-021-01204-1

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group

04 Mar 2021-Translational Psychiatry (Nature Publishing Group)-Vol. 11, Iss: 1, pp 156-156
Abstract: Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.

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Topics: Alcohol dependence (65%), Addiction (51%)

6 results found

Open accessJournal ArticleDOI: 10.1002/HBM.25438
Abstract: Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population-based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex-specific phenotypes in major brain diseases.

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Topics: Neuroimaging (53%), Population (52%)

2 Citations

Open accessJournal ArticleDOI: 10.3389/FNINS.2021.689601
Abstract: Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

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Topics: Dentate gyrus (65%), Neurogenesis (65%), Subgranular zone (64%) ... show more

1 Citations

Open accessJournal ArticleDOI: 10.1016/J.NICL.2021.102771
Abstract: Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.

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Topics: Alcohol use disorder (67%)

Journal ArticleDOI: 10.1016/J.PSCYCHRESNS.2021.111380
Simon Zhornitsky1, Shefali Chaudhary1, Thang M. Le1, Yu Chen1  +5 moreInstitutions (2)
Abstract: Epidemiological surveys suggest that excessive drinking is associated with higher risk of Alzheimer's disease (AD). The present study utilized data from the National Alzheimer's Coordinating Center to examine cognition as well as gray/white matter and ventricular volumes among participants with AD and alcohol use disorder (AD/AUD, n = 52), AD only (n = 701), AUD only (n = 67), and controls (n = 1283). AUD diagnosis was associated with higher Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in AD than in non-AD. AD performed worse on semantic fluency and Trail Making Test A + B (TMT A + B) and showed smaller total GMV, WMV, and larger ventricular volume than non-AD. AD had smaller regional GMV in the inferior/superior parietal cortex, hippocampal formation, occipital cortex, inferior frontal gyrus, posterior cingulate cortex, and isthmus cingulate cortex than non-AD. AUD had significantly smaller somatomotor cortical GMV and showed a trend towards smaller volume in the hippocampal formation, relative to non-AUD participants. Misuse of alcohol has an additive effect on dementia severity among AD participants. Smaller hippocampal volume is a common feature of both AD and AUD. Although AD is associated with more volumetric deficits overall, AD and AUD are associated with atrophy in largely distinct brain regions.

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Topics: Posterior cingulate (54%), Cingulate cortex (52%), Trail Making Test (50%) ... show more

Open accessJournal ArticleDOI: 10.3389/FCVM.2021.751421
Hongbai Wang1, Xiaoxiao Guo2, Xianlin Zhu, Yinan Li1  +4 moreInstitutions (2)
Abstract: Background: Postoperative delirium (POD) is common in patients following cardiac surgery. According to studies on non-cardiac surgery, males suffered from higher incidence of POD. However, there is no report about effect of gender differences on POD occurrence in cardiac surgery patients. The aim of this study was to investigate the effect of gender differences on POD occurrence in adult patients after cardiac valve surgery. Methods: This is a retrospective case-control study. We recorded the clinical data in adult patients who underwent elective cardiac valve surgery from May 2019 to October 2020. Univariate analysis was used to screen the potential risk factors. Collinearity analysis was conducted to detect overlapping predictor variables on the outcomes. A multivariate logistic regression with odds ratio (OR) and 95% confidence interval (CI) was used to identify the independent risk factors. The Hosmer-Lemeshow test was performed to show the good calibration of the logistic regression model. Results: In total, we recorded the perioperative data in 431 adult patients, including 212 males and 219 females. 60 patients suffered from POD, including 39 males and 21 females. 20 perioperative variables were selected, and ten were screened by univariate analysis. We did not detect the severe collinearity among the ten variables. Male gender was identified as a significant risk factor in POD occurrence in patients undergoing cardiac surgery (Adjusted OR: 2.38, 95% CI: 1.15 to 4.95, P=0.02). The Hosmer-Lemeshow test demonstrated good calibration of the logistic regression model (χ2=7.70, P=0.463). Besides, compared with females, the relationship of male and delirium subtypes was as follows: 1) hyperactive: adjusted OR: 3.33, 95% CI: 1.35 to 8.24, P=0.009; 2) hypoactive: adjusted OR: 0.55, 95% CI: 0.16 to 1.86, P=0.335; 3) mixed: adjusted OR: 4.95, 95% CI: 0.32 to 77.4, P=0.254. Conclusions: Male gender is an important risk factor in POD occurrence in patients following cardiac surgery. Furthermore, the incidence of hyperactive delirium is higher in males.

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Topics: Odds ratio (52%), Perioperative (51%), Univariate analysis (51%) ... show more


56 results found

Journal ArticleDOI: 10.1006/NIMG.1998.0395
01 Feb 1999-NeuroImage
Abstract: Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging. r 1999 Academic Press

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8,246 Citations

Journal ArticleDOI: 10.1016/J.NEUROIMAGE.2006.01.021
Rahul S. Desikan1, Florent Ségonne2, Bruce Fischl2, Bruce Fischl3  +10 moreInstitutions (7)
01 Jul 2006-NeuroImage
Abstract: In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.

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7,652 Citations

Journal ArticleDOI: 10.1016/S0140-6736(09)60746-7
Jürgen Rehm, Colin Mathers, Svetlana Popova1, Svetlana Popova2  +4 moreInstitutions (4)
27 Jun 2009-The Lancet
Abstract: Summary Alcohol consumption has been identified as an important risk factor for chronic disease and injury. In the first paper in this Series, we quantify the burden of mortality and disease attributable to alcohol, both globally and for ten large countries. We assess alcohol exposure and prevalence of alcohol-use disorders on the basis of reviews of published work. After identification of other major disease categories causally linked to alcohol, we estimate attributable fractions by sex, age, and WHO region. Additionally, we compare social costs of alcohol in selected countries. The net effect of alcohol consumption on health is detrimental, with an estimated 3·8% of all global deaths and 4·6% of global disability-adjusted life-years attributable to alcohol. Disease burden is closely related to average volume of alcohol consumption, and, for every unit of exposure, is strongest in poor people and in those who are marginalised from society. The costs associated with alcohol amount to more than 1% of the gross national product in high-income and middle-income countries, with the costs of social harm constituting a major proportion in addition to health costs. Overall, we conclude that alcohol consumption is one of the major avoidable risk factors, and actions to reduce burden and costs associated with alcohol should be urgently increased.

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Topics: Disease burden (57.99%), Poison control (51%)

2,895 Citations

Journal ArticleDOI: 10.1093/BIOMET/73.3.751
R. J. Simes1Institutions (1)
01 Dec 1986-Biometrika
Abstract: SUMMARY A modification of the Bonferroni procedure for testing multiple hypotheses is presented. The method, based on the ordered p-values of the individual tests, is less conservative than the classical Bonferroni procedure but is still simple to apply. A simulation study shows that the probability of a type I error of the procedure does not exceed the nominal significance level, a, for a variety of multivariate normal and multivariate gamma test statistics. For independent tests the procedure has type I error probability equal to a. The method appears particularly advantageous over the classical Bonferroni procedure when several highly-correlated test statistics are involved.

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Topics: Bonferroni correction (71%), Holm–Bonferroni method (67%), Per-comparison error rate (62%) ... show more

2,044 Citations

Open accessJournal ArticleDOI: 10.1016/S2215-0366(16)00104-8
George F. Koob1, Nora D. Volkow2Institutions (2)
Abstract: Summary Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.

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Topics: Incentive salience (59%), Addiction (59%), Reward system (54%) ... show more

1,356 Citations

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