@article{pmid24138923,

title = {Glycogen synthase kinase-3 overexpression replicates electroretinogram anomalies of offspring at high genetic risk for schizophrenia and bipolar disorder},

author = {Joëlle Lavoie and Marc Hébert and Jean-Martin Beaulieu},

doi = {10.1016/j.biopsych.2013.08.035},

issn = {1873-2402},

year  = {2014},

date = {2014-07-01},

journal = {Biol Psychiatry},

volume = {76},

number = {2},

pages = {93--100},

abstract = {BACKGROUND: Electroretinogram (ERG) anomalies occur in patients with psychiatric disorders and represent potential biomarkers for diagnosis. For instance, decreased rod ERG (b-wave amplitude at Vmax) is a biological endophenotype in young offspring at high genetic risk (HR) for schizophrenia (SZ) and bipolar disorder (BD). Also, a decrease in cone a-wave and rod a- and b- wave was observed in SZ patients. However, the biological underpinning of these anomalies remains unknown. Several genetic variants associated with enhanced risk for SZ and/or BD can activate glycogen synthase kinase-3 isozymes (GSK3α and β). Here we examined the potential contribution of GSK3α and β in the modulation of the ERG.nnMETHODS: Cone and rod ERGs were recorded in mice having increased (prpGSK3β mice) or reduced (GSK3β(+/-) mice) GSK3β expression and in GSK3α knockout (KO) mice.nnRESULTS: In prpGSK3β mice, we observed a decrease in rod b-wave amplitude at Vmax, whereas enhanced b-wave amplitude at Vmax was found in GSK3β(+/-) mice. An increase in cone a- and b-wave amplitude at Vmax and in rod b-wave amplitude at Vmax was observed in GSK3α-KO mice.nnCONCLUSIONS: GSK3 expression modulates some ERG parameters. The phenotype observed in prpGSK3β mice is consistent with observations made in HRs. ERG anomalies observed in GSK3β(+/-) and GSK3α-KO mice confirm an association between the rod and cone b-wave amplitude and the expression of GSK3 isozymes. Changes in GSK3 expression or activity may explain some ERG anomalies in HRs and patients, thus supporting the biological validity of ERG measurements as a valuable biomarker for psychiatric research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23305992,

title = {The electroretinogram as a biomarker of central dopamine and serotonin: potential relevance to psychiatric disorders},

author = {Joëlle Lavoie and Placido Illiano and Tatyana D Sotnikova and Raul R Gainetdinov and Jean-Martin Beaulieu and Marc Hébert},

doi = {10.1016/j.biopsych.2012.11.024},

issn = {1873-2402},

year  = {2014},

date = {2014-03-01},

journal = {Biol Psychiatry},

volume = {75},

number = {6},

pages = {479--486},

abstract = {BACKGROUND: Dysfunctions in brain dopamine and serotonin neurotransmission are believed to be involved in the etiology of psychiatric disorders, and electroretinogram (ERG) anomalies have been reported in psychiatric patients. The goal of this study was to evaluate whether ERG anomalies could result from central dopamine or serotonin dysfunctions or from changes in the retinal bioavailability of these neurotransmitters.nnMETHOD: Photopic and scotopic ERGs were recorded in R439H tryptophan hydroxylase 2 knockin (Tph2-KI) mice that have an approximately 80% decrease in brain serotonin and dopamine transporter knockout (DAT-KO) mice showing a fivefold increase in brain extracellular dopamine. Dopamine and serotonin retinal and striatal tissue content were also measured. The role of dopamine D1 receptors (D1R) and D2 receptors (D2R) in the ERG responses was evaluated in D1R-KO and D2R-KO mice.nnRESULTS: An increase in photopic b-wave implicit time was observed in Tph2-KI mice (wildtype = 24.25 msec, KI = 25.22 msec; p = .011). The DAT-KO mice showed a decrease in rod sensitivity (wildtype =-1.97 log units, KO =-1.81 log units; p = .014). In contrast to remarkable alterations in brain levels, no changes in dopamine and serotonin retinal content were found in DAT-KO and Tph2-KI mice, respectively. The D1R-KO mice showed anomalies in photopic and scotopic maximal amplitude, whereas D2R-KO mice showed higher oscillatory potentials relative contribution to the b-wave amplitude.nnCONCLUSION: Alterations in central dopamine and serotonin neurotransmission can affect the ERG responses. The ERG anomalies reported in psychiatric disorders might serve as biomarkers of central monoaminergic dysfunction, thus promoting ERG measurements as a useful tool in psychiatric research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24121062,

title = {The brain through the retina: the flash electroretinogram as a tool to investigate psychiatric disorders},

author = {Joëlle Lavoie and Michel Maziade and Marc Hébert},

doi = {10.1016/j.pnpbp.2013.09.020},

issn = {1878-4216},

year  = {2014},

date = {2014-01-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {48},

pages = {129--134},

abstract = {Investigating the living brain remains one of the major obstacles in psychiatry research in order to better understand the biological underpinning of brain disorders. Novel approaches are needed to study brain functions indirectly. Since it is part of the central nervous system, retinal functions as measured with the flash electroretinogram (ERG) may reflect the central dysfunctions reported in psychiatric disorders. This review describes the flash ERG anomalies reported in patients with psychiatric disorders such as seasonal affective disorder, schizophrenia, autism spectrum disorder and drug addiction and discusses how changes in retinal functions might be used as biomarkers for psychiatric disorder as well as a potential aid to diagnosis in psychiatry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24381372,

title = {Aging reduces the stimulating effect of blue light on cognitive brain functions},

author = {Véronique Daneault and Marc Hébert and Geneviève Albouy and Julien Doyon and Marie Dumont and Julie Carrier and Gilles Vandewalle},

doi = {10.5665/sleep.3314},

issn = {1550-9109},

year  = {2014},

date = {2014-01-01},

journal = {Sleep},

volume = {37},

number = {1},

pages = {85--96},

abstract = {STUDY OBJECTIVES: Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however.nnDESIGN: Cross-sectional study.nnSETTING: Functional Neuroimaging Unit, University of Montreal Geriatric Institute.nnPARTICIPANTS: Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study.nnINTERVENTION: Blue light administration.nnMEASUREMENTS: We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light.nnRESULTS: Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals.nnCONCLUSION: The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23919927,

title = {Glycogen synthase kinase-3β haploinsufficiency lengthens the circadian locomotor activity period in mice},

author = {Joëlle Lavoie and Marc Hébert and Jean-Martin Beaulieu},

doi = {10.1016/j.bbr.2013.08.001},

issn = {1872-7549},

year  = {2013},

date = {2013-09-01},

journal = {Behav Brain Res},

volume = {253},

pages = {262--265},

abstract = {The mood stabiliser drug lithium has been reported to impact circadian rhythms in vertebrates. Among several putative therapeutic molecular targets, direct inhibition of glycogen synthase kinase-3 beta (GSK3β) by lithium has been proposed to underlie its effects on circadian physiology. Here we study the effect of GSK3β haploinsufficiency on the circadian locomotor activity in mice during a free-running period in comparison to wildtype littermates (WT). Mice were housed individually to record their circadian wheel running activity and were entrained to a 12h light/12h dark cycle for 14 days and then placed under constant darkness for 14 days to allow free-running. During the free-running phase, the circadian locomotor activity period of GSK3β(+/-) was significantly lengthened (23.83±0.05h) when compared to the WT mice (23.54±0.10h; p=0.0374). No significant difference in locomotor activity was observed. Knowing that GSK3β interacts with most of the core clock components, these data suggest that GSK3β acts as a critical intrinsic regulator of the circadian clock and plays an important role in regulating its period in response to lithium treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20847757,

title = {Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular dystrophy: randomized clinical trial},

author = {Thomas K M Lee and M Thomas Clandinin and Marc Hébert and Ian M MacDonald},

doi = {10.3129/i10-028},

issn = {1715-3360},

year  = {2010},

date = {2010-10-01},

journal = {Can J Ophthalmol},

volume = {45},

number = {5},

pages = {514--519},

abstract = {OBJECTIVE: Best disease is a slowly progressive macular dystrophy that typically has an onset in early childhood. Multiple lines of evidence suggest that dietary docosahexaenoic acid (DHA) protects against the development of macular degeneration. Our trial tested the effect of an oral supplement of DHA on visual function in patients with Best disease.nnDESIGN: Double-masked, randomized, placebo-controlled, crossover clinical trial.nnPARTICIPANTS: Eight patients with Best disease.nnMETHODS: Patients were given either an oral supplement of DHA (20 mg/kg daily) or placebo. Primary outcome measures were the multifocal electroretinogram (mfERG) and electro-oculogram (EOG). Plasma DHA was tracked along with visual acuity (Early Treatment Diabetic Retinopathy Study chart), VF-14 scores, and Humphrey visual fields.nnRESULTS: All 8 patients had increased plasma DHA levels (2-3 fold) during periods of DHA supplementation compared with periods without supplementation. Differences in visual acuity, VF-14 scores, and EOG Arden ratios during periods with and without DHA supplementation were all statistically insignificant. A positive correlation was found between the plasma concentration of DHA and mfERG amplitudes, but amplitude changes during the treatment periods were not significant. A carryover effect of DHA supplementation was a confounding error.nnCONCLUSIONS: Our pilot trial of DHA supplementation in 8 patients with Best disease did not demonstrate an improvement in macular function. An expanded trial would be needed to examine the full effects of DHA supplementation on visual function in Best disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19833322,

title = {Retinal response to light in young nonaffected offspring at high genetic risk of neuropsychiatric brain disorders},

author = {Marc Hébert and Anne-Marie Gagné and Marie-Eve Paradis and Valérie Jomphe and Marc-André Roy and Chantal Mérette and Michel Maziade},

doi = {10.1016/j.biopsych.2009.08.016},

issn = {1873-2402},

year  = {2010},

date = {2010-02-01},

journal = {Biol Psychiatry},

volume = {67},

number = {3},

pages = {270--274},

abstract = {BACKGROUND: In neuropsychiatric brain disorders, such as schizophrenia (SZ) and bipolar disorder (BD), the biased effect of chronic drug therapy and the toxic effect of illness once installed constitute obstacles to the identification of valid biomarkers. Such biomarkers could lie at the level of retinal function where anomalies have already been reported in adults suffering from neuropsychiatric disorders. Here, we report a specific electroretinographic (ERG) anomaly in young nonaffected and nonmedicated offspring at high genetic risk (HR) of these disorders.nnMETHODS: Electroretinography was performed in 29 HR offspring having one parent affected by DSM-IV SZ or BD (mean age: 20.8 years, SD 4.4) and 29 healthy control subjects (mean age: 20.6 years, SD 4.2). The HRs' parents descended from multigenerational families affected by SZ or BD.nnRESULTS: Rod ERG (b-wave amplitude at V(max)) in HRs was significantly lower than control subjects (p < .0001; effect size of -1.47), whereas the cone ERG V(max) showed no difference (p = .27). No effects of gender, age, and seasons of testing were observed. The anomaly in retinal response (rod V(max) b-wave amplitude) was observed independently of parents' diagnosis (SZ; p = .007, effect size of -1.09; BD: p < .0001, effect size of -1.88) and was present in both the younger and older HRs (effect size of -1.6 and -1.8, respectively).nnCONCLUSIONS: A rod retinal response anomaly before the age of the disease incidence may represent an early and specific biomarker of risk with meaning for further genetic and prevention research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12608515,

title = {Autosomal dominant macular dystrophy in a large Canadian family},

author = {Larry A Donoso and Gregory Hageman and Arcilee Frost and Val Sheffield and John Beck and Marc Hébert and Ian M MacDonald},

doi = {10.1016/s0008-4182(03)80006-6},

issn = {0008-4182},

year  = {2003},

date = {2003-02-01},

journal = {Can J Ophthalmol},

volume = {38},

number = {1},

pages = {33--40},

abstract = {BACKGROUND: We studied a large Canadian family (178 total family members) spanning seven generations with autosomal dominant macular dystrophy. We performed a study to identify the gene mutation responsible for the disease in the family.nnMETHODS: Participating family members were evaluated clinically. Genetic linkage, genotyping, mutation screening and an extensive genealogic investigation were performed.nnRESULTS: The common clinical findings in affected family members included progressive early- to mid-onset visual loss and extensive areas of central chorioretinal atrophy. Two-point linkage analysis indicated linkage to chromosome 6p. Direct DNA sequencing showed a C/T transition in codon 172 of the retinal degeneration slow (RDS) gene creating an amino acid change to Arg172Trp. Haplotype analysis of affected family members using microsatellite markers distributed around the RDS gene locus revealed that the markers were not conserved when compared to members of British families with the Arg172Trp mutation. Genealogic studies indicated the family immigrated to Canada from Ireland in 1843.nnINTERPRETATION: A newly identified large family with autosomal dominant macular dystrophy is described. The phenotypic appearance of the fundus is similar to that of previously described patients with an Arg172Trp mutation in the RDS gene. Haplotype analysis of markers spanning the disease locus identified a new founder for this mutation. The identification of the disease-causing gene in this family allows for better genetic counselling for patients with this condition and provides a basis to distinguish clinically similar types of macular dystrophy based on the clinical phenotype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12390501,

title = {The effects of prior light history on the suppression of melatonin by light in humans},

author = {Marc Hébert and Stacia K Martin and Clara Lee and Charmane I Eastman},

doi = {10.1034/j.1600-079x.2002.01885.x},

issn = {0742-3098},

year  = {2002},

date = {2002-11-01},

journal = {J Pineal Res},

volume = {33},

number = {4},

pages = {198--203},

abstract = {We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright-light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 +/- 0.4 hr of bright light per day (by going outside and using light boxes indoors). During the dim week, they wore dark goggles (about 2% light transmission) when outside during daylight and spent 1.4 +/- 0.9 hr per day outside. Saliva samples were obtained every 30 min for 7 hr in dim light (<15 lux) on two consecutive nights (baseline and test night) at the end of each week. On the test night, 500 lux was presented for 3 hr in the middle of the collection period to suppress melatonin. There was significantly more suppression after the dim week compared with after the bright week (to 53 versus 41% of the baseline night values, P < 0.05). However, there were large individual differences, and the difference between the bright and dim weeks was most pronounced in seven of the 12 subjects. Possible reasons for these individual differences are discussed, including the possibility that 1 wk was not long enough to change light sensitivity in some subjects. In conclusion, this study suggests that the circadian system's sensitivity to light can be affected by a recent change in light history.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}