PMID- 27996307
OWN - NLM
STAT- MEDLINE
DCOM- 20180205
LR  - 20180814
IS  - 1525-6073 (Electronic)
IS  - 0742-0528 (Linking)
VI  - 34
IP  - 2
DP  - 2017
TI  - Clock genes associate with white matter integrity in depressed bipolar patients.
PG  - 212-224
LID - 10.1080/07420528.2016.1260026 [doi]
AB  - Human genetic studies have implicated specific genes that constitute the 
      molecular clock in the manifestation of bipolar disorder (BD). Among the clock 
      genes involved in the control system of circadian rhythms, CLOCK 3111 T/C and 
      Period3 (PER3) influence core psychopathological features of mood disorders, such 
      as patterns of sleep, rest, and activity, diurnal preference, cognitive 
      performances after sleep loss, age at the onset of the illness, and response to 
      antidepressant treatment. Furthermore, several studies pointed out that bipolar 
      symptomatology is associated with dysfunctions in white matter (WM) integrity, 
      suggesting these structural alterations as a possible biomarker of the disorder. 
      We hypothesise that CLOCK and PER3 polymorphisms could be potential factors 
      affecting WM microstructure integrity in bipolar patients. The relationship 
      between these clock genes and DTI measures of WM integrity in a sample of 140 (53 
      M; 87 F) patients affected by BD type I was studied. Tract-based spatial 
      statistics analyses on DTI measures of WM integrity were performed for each clock 
      gene polymorphism, between the genetic groups. We accounted for the effect of 
      nuisance covariates known to influence WM microstructure: age, sex, lithium 
      treatment, age at the onset of the illness, and the number of illness episodes. 
      We found that compared to T homozygotes, CLOCK C carriers showed a widespread 
      increase of the mean diffusivity in several WM tracts. Compared with PER3(5/5) 
      homozygotes, PER3(4/4) homozygotes showed significantly increased radial 
      diffusivity and reduced fractional anisotropy in several brain WM tracts. No 
      significant difference was observed between heterozygotes and the other 
      subgroups. Altogether, this pattern of results suggests WM disruption in CLOCK C 
      carrier and in PER3(4) homozygotes. Sleep promotes myelination and 
      oligodendrocyte precursor cell proliferation and associates with higher 
      expression of genes coding for phospholipid synthesis and myelination in 
      oligodendrocytes. These clock genes play a pivotal role in maintaining circadian 
      rhythms and the sleep-wake cycle. Thus, it may be suggested that CLOCK 
      rs1801260*C and PER3(4/4) influence myelination processes by regulating sleep 
      quality and quantity.
FAU - Bollettini, Irene
AU  - Bollettini I
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
AD  - c PhD program in Philosophy and Sciences of Mind , University Vita-Salute San 
      Raffaele , Milan , Italy.
FAU - Melloni, Elisa Maria Teresa
AU  - Melloni EM
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
AD  - d PhD program in Molecular Medicine , University Vita-Salute San Raffaele , Milan 
      , Italy.
FAU - Aggio, Veronica
AU  - Aggio V
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
FAU - Poletti, Sara
AU  - Poletti S
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
FAU - Lorenzi, Cristina
AU  - Lorenzi C
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
FAU - Pirovano, Adele
AU  - Pirovano A
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
FAU - Vai, Benedetta
AU  - Vai B
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
AD  - e PhD program in Evolutionary Psychopathology , Libera Universita Maria SS. 
      Assunta , Rome , Italy.
FAU - Dallaspezia, Sara
AU  - Dallaspezia S
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
FAU - Colombo, Cristina
AU  - Colombo C
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
FAU - Benedetti, Francesco
AU  - Benedetti F
AD  - a Department of Clinical Neurosciences , Scientific Institute and University 
      Vita-Salute San Raffaele , Milan , Italy.
AD  - b C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo) , 
      University Vita-Salute San Raffaele , Milan , Italy.
LA  - eng
PT  - Journal Article
DEP - 20161220
PL  - England
TA  - Chronobiol Int
JT  - Chronobiology international
JID - 8501362
RN  - 0 (Antidepressive Agents)
RN  - 0 (PER3 protein, human)
RN  - 0 (Period Circadian Proteins)
RN  - EC 2.3.1.48 (CLOCK Proteins)
RN  - EC 2.3.1.48 (CLOCK protein, human)
SB  - IM
MH  - Adult
MH  - Anisotropy
MH  - Antidepressive Agents/therapeutic use
MH  - Bipolar Disorder/*pathology
MH  - Brain Mapping/methods
MH  - CLOCK Proteins/*genetics
MH  - Cell Proliferation
MH  - Circadian Rhythm
MH  - Depression/*pathology
MH  - Female
MH  - Genotype
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Male
MH  - Middle Aged
MH  - Myelin Sheath/metabolism
MH  - Period Circadian Proteins/*genetics
MH  - Sleep
MH  - Sleep Wake Disorders
MH  - White Matter/*pathology
OTO - NOTNLM
OT  - Bipolar depression
OT  - circadian rhythms
OT  - clock genes
OT  - diffusion tensor imaging
OT  - myelin alteration
EDAT- 2016/12/21 06:00
MHDA- 2018/02/06 06:00
CRDT- 2016/12/21 06:00
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2018/02/06 06:00 [medline]
PHST- 2016/12/21 06:00 [entrez]
AID - 10.1080/07420528.2016.1260026 [doi]
PST - ppublish
SO  - Chronobiol Int. 2017;34(2):212-224. doi: 10.1080/07420528.2016.1260026. Epub 2016 
      Dec 20.