title: Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency.
abstract: Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression.
authors.affiliation: Institute of Cellular Medicine (Hepatology), Newcastle University, William Leech Building, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK, david.sheridan@ncl.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Sheridan
authors.forename: S H
authors.initials: SH
authors.lastname: Bridge
authors.forename: M M E
authors.initials: MM
authors.lastname: Crossey
authors.forename: D J
authors.initials: DJ
authors.lastname: Felmlee
authors.forename: H C
authors.initials: HC
authors.lastname: Thomas
authors.forename: R D G
authors.initials: RD
authors.lastname: Neely
authors.forename: S D
authors.initials: SD
authors.lastname: Taylor-Robinson
authors.forename: M F
authors.initials: MF
authors.lastname: Bassendine
mesh_terms: D000328:Adult; D001007:Anxiety / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D001057:Apolipoproteins E / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003863:Depression / Q000097:blood* / Q000188:drug therapy / Q000523:psychology*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000523:psychology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D001057:Apolipoproteins E; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D002784:Cholesterol