title: CLOCK gene variants associated with the discrepancy between subjective and objective severity in bipolar depression.
abstract: The discrepancy between subjective and objective severity of depressive syndromes has been proposed as a predictor of treatment outcome and suicidal risk in depression, and is associated with depressive cognitive distortions. A recent study reported that evening-type depressed patients showed higher depressive cognitions than morning-type patients. Therefore, it can be hypothesized that genetic factors affecting evening preference, such as carrying of the CLOCK rs1801260*C allele, may influence the discrepancy.
  
  
  
  We tested this hypothesis in 132 patients affected by a major depressive episode in the course of bipolar disorder. The severity of depression was evaluated using self-rated (Beck Depression Inventory: BDI) and observer-rated (Hamilton Depression Rating Scale: HDRS) measures. The BDI-HDRS discrepancy score was calculated and the effects of the rs1801260 polymorphism on this score and on depressive cognitive distortions, as measured on the Cognitions Questionnaire, were examined.
  
  
  
  The rs1801260*C carriers showed higher BDI-HDRS discrepancy scores than T/T homozygotes. Mediation analysis using bootstrapping procedures revealed that the dimension of depressive cognition "hopelessness" fully mediates the association between the rs1801260 polymorphism and the BDI-HDRS discrepancy.
  
  
  
  Many gene polymorphisms other than CLOCK rs1801260 may also influence the BDI-HDRS discrepancy and depressive cognitive distortions.
  
  
  
  Our current results suggest that factors affecting the biological clock can influence the "non-clock" psychopathological features of mood disorders.
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; Department of Psychiatry, Nihon University School of Medicine, Tokyo, Japan. Electronic address: suzuki.masahiro94@nihon-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Dallaspezia
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Locatelli
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lorenzi
authors.affiliation: Department of Psychiatry, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D056926:CLOCK Proteins / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000235:genetics / Q000523:psychology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D056926:CLOCK Proteins
keywords: Bipolar disorder; CLOCK; Clinical rating scales; Cognitive distortion; Depression