Research Article Details
| Article ID: | A36955 |
| PMID: | 16868265 |
| Source: | Psychosom Med |
| Title: | Depression, anxiety, and nonalcoholic steatohepatitis. |
| Abstract: | OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a morbid liver disease with limited treatment. Depression and anxiety have been associated recently with insulin resistance and inflammatory states, factors that are relevant to the development of NASH. We hypothesized that depression and anxiety would be more prevalent in NASH patients and predict more severe histological findings on liver biopsy. METHODS: Histories of major depressive disorder (MDD) and generalized anxiety disorder (GAD) were determined using a structured interview and DSM-IV criteria in 36 NASH subjects and 36 matched controls without liver disease who had undergone cholecystectomy. Histological changes on liver biopsy in NASH subjects were age-adjusted and compared in subjects with and without psychiatric disorders. A multivariate model incorporating other potential risk factors for NASH (female sex, body mass index, waist-to-hip ratio, and presence of diabetes) was used to determine independent effects of MDD and GAD on severity of histological findings. RESULTS: NASH subjects had significantly increased lifetime rates of MDD (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.4-10.2; p = .018) and GAD (OR 5.0, 95% CI, 1.7-14.9; p = .005). The onset of psychiatric illness preceded diagnosis of liver disease by 18 to 20 years. Each psychiatric disorder was associated with more severe histological features (p < .05 for each), the effect of GAD on fibrosis stage persisting in the multivariate model. CONCLUSIONS: MDD and GAD are overrepresented in NASH subjects and are associated with more advanced liver histological abnormalities. Additional investigation will be required to determine if depression and anxiety affect the development or progression of NASH and serve as modifiable risk factors. |
| DOI: | 10.1097/01.psy.0000221276.17823.df |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I17 | 1596 | Mental depression | Mental depression | disease of mental health/ cognitive disorder/ mood disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |