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Antoine Douaihy

Publications and source records attributed to Antoine Douaihy.

5 recordsLinked to original sources
PubMed2025

Global Changes in Gene Expression and Splicing in Alcoholic Liver Disease.

Alcohol use disorder is a widespread illness commonly leading to alcoholic liver disease (ALD) and cirrhosis with an increased incidence of hepatocellular carcinoma (HCC), but the mechanisms of alcohol-related oncogenesis in the liver are incompletely understood. We tested the hypothesis that ALD predisposes to HCC via dysregulation of splicing. RNA sequencing was performed on liver biopsies from patients with different stages of ALD: early alcoholic steatohepatitis (eASH), non-severe alcoholic hepatitis (nsAH), and severe alcoholic hepatitis (sAH); furthermore, explants were collected from patients who underwent liver transplantation due to sAH (exAH). We found that alcohol caused widespread changes in transcriptome in all stages of ALD: among ~ 58,000 analyzed genomic features, ~ 4,900 were altered in eASH, ~ 9,100 - in nsAH, 14,100 - in sAH, and ~ 14,300 - in exAH. We observed thousands of missplicing events in all hepatic conditions, with mutually exclusive exons (MEE) being the most common event and exon skipping (ES) - second most common event. Analysis of ~ 600,000 exons revealed that ALD is associated with a genome-wide effect on exon expression, with ~ 50,000 exons being differentially expressed in eASH, ~ 130,000 - in nsAH, ~ 150,000 - in sAH, and ~ 120,000 - in exAH. To determine whether alcohol directly perturbs splicing, we subjected rats to alcohol vapor for 7 weeks and found that the expression of multiple snRNAs was drastically decreased, while expression of splicing factors was not affected. Screening of oncogenes and tumor suppressors, commonly involved in HCC pathogenesis, revealed that ALD affected the hepatic expression and/or splicing of most of these cancer-related genes. In summary, it appears that alcohol causes profound genome-wide changes in gene expression and splicing in the liver, likely via affecting the spliceosome. This results in altered expression and missplicing of key oncogenes and tumor suppressors involved in HCC, suggesting a novel mechanism of oncogenesis in the liver of patients with ALD.

alcohol use disorder↗
PubMed2006

Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study.

OBJECTIVE: The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence. METHOD: Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use. Patients were started on open-label divalproex. After stabilization on divalproex sodium, weekly assessments were undertaken for 8weeks. Subjects also attended dual recovery counseling. RESULTS: The results revealed significant improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use severity index, % alcohol abstinent days, drinks per drinking day, marijuana use and cigarettes smoking. They also had significant improvement on manic, depressive, and sleep symptoms and on functioning. There were no reported adverse events or increases in liver function tests. CONCLUSION: The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence. Double-blind, placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted.

Adolescent↗
PubMed2005

Patient characteristics and treatment implications of marijuana abuse among bipolar alcoholics: results from a double blind, placebo-controlled study.

OBJECTIVE: Marijuana abuse, primarily a disorder of adolescents and young adults, is highly prevalent among patients with severely ill psychiatric population, especially those with bipolar disorder. Additional marijuana abuse may impact on the clinical presentation of bipolar illness and may potentially act as mediator of treatment response in this population. However, the characterization of bipolar disorder patients with additional marijuana abuse and the impact of such abuse on treatment outcome has been rarely examined. The aim of this study was to characterize bipolar alcoholic patients with comorbid marijuana abuse and test the impact of marijuana abuse on alcohol and mood outcome of patients with bipolar disorder and comorbid alcohol dependence. METHOD: We conducted secondary analyses of a randomized, double blind, placebo-controlled trial testing valproate in 52 bipolar alcoholics. Subjects had a comprehensive assessment at baseline using structured diagnostic assessments, and they were then assessed every 2 weeks for 24 weeks. RESULTS: Twenty-five subjects (48%) reported marijuana abuse. Those with co-occurring marijuana abuse were younger, had fewer years of education, and had significantly higher number of additional psychiatric comorbidity. They also had more severe alcohol and other drug use and were significantly more likely to present in the manic phase. The mixed model indicated that the placebo-treated marijuana abuse group had the worst alcohol use outcome. CONCLUSIONS: Marijuana abuse among patients with bipolar disorder and alcohol dependence is associated with higher degree of severity of alcohol and other drugs of abuse and may negatively impact on alcohol treatment outcome.

Adolescent↗
PubMed2004

Concurrent alcohol and cocaine dependence impact on physical health among psychiatric patients.

The aim of this study was to examine the association between active, concomitant cocaine and alcohol dependence and the prevalence and patterns of comorbid physical disorders in a sample of substance abusing hospitalized psychiatric patients. Three groups of patients (concomitant cocaine and alcohol dependence (AD + CD) (N = 38), alcohol dependence (AD) only (N = 38), and cocaine dependence (CD) only (N = 25)) consecutively admitted to a psychiatric-substance abuse dual diagnosis unit were comparatively examined for the frequency of comorbid physical disorders diagnoses, including viral hepatitis, sexually transmitted diseases, and on liver function tests and electrocardiographic abnormalities. The results indicated that the concomitant alcohol and cocaine dependence group had higher rates of multiple physical disorders and also of multiple hepatitis infections than either the alcohol-only or the cocaine-only groups.

Academic Medical Centers↗