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Severity of alcohol use disorder influences sex differences in sleep, mood, and brain functional connectivity impairments.

ABSTRACT: Growing evidence suggests greater vulnerability of women than men to the adverse effects of alcohol on mood and sleep. However, the underlying neurobiological mechanisms are still poorly understood. Here, we examined sex difference in resting state functional connectivity in alcohol use disorder using a whole-brain data driven approach and tested for relationships with mood and self-reported sleep. To examine whether sex effects vary by severity of alcohol use disorder, we studied two cohorts: non-treatment seeking n = 141 participants with alcohol use disorder (low severity; 58 females) from the Human Connectome project and recently detoxified n = 102 treatment seeking participants with alcohol use disorder (high severity; 34 females) at the National Institute on Alcohol Abuse and Alcoholism. For both cohorts, participants with alcohol use disorder had greater sleep and mood problems than healthy control, whereas sex by alcohol use effect varied by severity. Non-treatment seeking females with alcohol use disorder showed significant greater impairments in sleep but not mood compared to non-treatment seeking males with alcohol use disorder, whereas treatment-seeking females with alcohol use disorder reported greater negative mood but not sleep than treatment-seeking males with alcohol use disorder. Greater sleep problems in non-treatment seeking females with alcohol use disorder were associated with lower cerebello-parahippocampal functional connectivity, while greater mood problems in treatment-seeking females with alcohol use disorder were associated with lower fronto-occipital functional connectivity during rest. The current study suggests that changes in resting state functional connectivity may account for sleep and mood impairments in females with alcohol use disorder. The effect of severity on sex differences might reflect neuroadaptive processes with progression of alcohol use disorder and needs to be tested with longitudinal data in the future.

SUBMITTER: Zhang R

PROVIDER: S-EPMC9251604 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Autism spectrum disorder (ASD) is more prevalent in males than females, but the underlying neurobiology of this sex bias remains unclear. Given its involvement in ASD, its role in sensorimotor, cognitive, and socio-affective processes, and its developmental sensitivity to sex hormones, the cerebellum is a candidate for understanding this sex difference. The current study used resting-state functional magnetic resonance imaging (fMRI) to investigate sex-dependent differences in cortico-cerebellar organization in ASD. We collected resting-state fMRI scans from 47 females (23 ASD, 24 controls) and 120 males (56 ASD, 65 controls). Using a measure of global functional connectivity (FC), we ran a linear mixed effects analysis to determine whether there was a sex-by-diagnosis interaction in resting-state FC. Subsequent seed-based analyses from the resulting clusters were run to clarify the global connectivity effects. Two clusters in the bilateral cerebellum exhibited a diagnosis-by-sex interaction in global connectivity. These cerebellar clusters further showed a pattern of interaction with regions in the cortex, including bilateral fusiform, middle occipital, middle frontal, and precentral gyri, cingulate cortex, and precuneus. Post hoc tests revealed a pattern of cortico-cerebellar hyperconnectivity in ASD females and a pattern of hypoconnectivity in ASD males. Furthermore, cortico-cerebellar FC in females more closely resembled that of control males than that of control females. These results shed light on the sex-specific pathophysiology of ASD and are indicative of potentially divergent neurodevelopmental trajectories for each sex. This sex-dependent, aberrant cerebellar connectivity in ASD might also underlie some of the motor and/or socio-affective difficulties experienced by members of this population, but the symptomatic correlate(s) of these brain findings remain unknown. Clinical Trial Registration: www.ClinicalTrials.gov, NIH Clinical Study Protocol 10-M-0027 (ZIA MH002920-09) identifier #NCT01031407.

Project description:BackgroundDiffusion-weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol-dependent populations. In addition, information on WM deficits in currently drinking, nontreatment-seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD).MethodsThirty-eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in-house preprocessing of the DWI data, FA images were analyzed with tract-based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption.ResultsSmoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family-wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = -0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions.ConclusionsNTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self-reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol-dependent individuals, after controlling for the key variable of cigarette smoking.

Project description:BackgroundSleep plays an important role in vulnerability to mood disorders. However, despite the existence of sex differences in vulnerability to mood disorders, no study has yet investigated the sex effect on sleep network organization and its potential involvement in vulnerability to mood disorders. The aim of our study was to empirically investigate the sex effect on network organization during REM and slow-wave sleep using the effective connectivity measured by Granger causality.MethodsPolysomnographic data from 44 healthy individuals (28 men and 16 women) recruited prospectively were analysed. To obtain the 19 × 19 connectivity matrix of all possible pairwise combinations of electrodes by Granger causality method from our EEG data, we used the Toolbox MVGC multivariate Granger causality. The computation of the network measures was realized by importing these connectivity matrices into EEGNET Toolbox.ResultsIn men and women, all small-world coefficients obtained are compatible with a small-world network organization during REM and slow-wave sleep. However, compared to men, women present greater small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage, which indicates the presence of a small-world network organization less marked during REM sleep as well as for all EEG bands during this sleep stage in women. In addition, in women, these small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage are positively correlated with the presence of subclinical symptoms of depression.ConclusionsThus, the highlighting of these sex differences in network organization during REM sleep indicates the presence of differences in the global and local processing of information during sleep between women and men. In addition, this small-world network organization less marked during REM sleep appears to be a marker of vulnerability to mood disorders specific to women, which opens up new perspectives in understanding sex differences in the occurrence of mood disorders.

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Severity of alcohol use disorder influences sex differences in sleep, mood, and brain functional connectivity impairments.

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