ArchT inhibition reducedFFTpower near 40Hz from no-
inhibitionmean of 1.88±0.4 to 1.22±0.2microvolts-squared.
Moreover, preliminary data indicated a 23% reduction
in arousals fromNREM by loudwhitenoise sounds (30
dB>background). Hypercarbia:With bilateral ArchTBFPV
inhibition, NREMEEG arousal latencieswith hypercarbia in
5micewere significantly increased (6.5±0.8swithoutArchT,
13.1±1.7swithArchT, paired t-test, p=0.002), an increase
of 101.5%.Additionally, under control conditions, arousals
occurred at ameanambient CO2 level of 6.3±0.6%, but
when bilateral ArchTBFPV inhibitionwas applied, theCO2
level for arousal was significantly increased to 8.2±0.8%
(paired t-test, p=0.025).
Conclusion:
Inhibition of BF pvGABAneurons confirms
their key role in cortical activation from both sensory
(auditory) and visceral (respiratory) stimuli.
Support:
Dept. of VeteransAffairs (VAmerit), MH039683,
HL095491 (Proj.3). MH094803, NS079866.
LBA3
1:10pm –1:25pm
Non-visual Effects of Light onMoodThrough
theMelanopsinPathway inSeasonal
Depression
RoeckleinKA
1,2
, MillerMA
1
, DonofrySD
1
, Hasler BP
3
,
FranzenPL
3
, GamlinPD
4
1
Department of Psychology, University of Pittsburgh,
Pittsburgh, PA, USA,
2
TheCenter for theNeural Basis of
Cognition, Pittsburgh, PA, USA,
3
Department of Psychiatry,
University of PittsburghSchool of Medicine, University
of Pittsburgh, Pittsburgh, PA, USA,
4
Department of
Ophthalmology, School of Medicine, University ofAlabama,
Birmingham,AL, USA
Introduction:
Individual differences in the effect of light
onmood, mediated by retinal subsensitivity, may explain
seasonal affectivedisorder (SAD). Previouslywe found
reduced retinal melanopsin cell responding inSAD (post-
illumination pupil response, PIPR). However, the effect of
light exposure prior to testing thePIPR could be significant
given differential light exposure inSAD, and has not yet
been studied.
Methods:
Participants include 33 individualswithSAD
(84%Female; age
M
=38.4,
SD
=13.6), and 17 controls
(73%Female; age
M
=34.1,
SD
=12.8). ThePIPRwas
assessed in summer andwinter. Light exposures (1 sec)
were 15.78nm full width half-maximum (FWHM 632.9nm)
and 22.68nmFWHM (467.7nm) and 13.5 logPhotons/
cm
2
/s retinal irradiance accounting for age-related blue light
absorption. Light exposure in the days prior to testingwas
measured using actigraphy.
Results:
Total photons on the day of PIPR testing
accounted for significant variation inPIPR values inSAD
but not controls. Blue total photons accounted for the
greatest proportion of variance inPIPR (
R
2
=0.318, β=0.39,
p
=0.013), and remained a predictor (
R
2
change=0.14,
p
=0.013) when controlling for gender, chronotype, and
time sincewake. Furthermore, thePIPRwas lower inSAD
compared to controls (
F
(1,50.5)=6.34,
p
<0.05) and lower in
evening chronotypes (
F
(1,53.2)=13.7,
p
<0.001) evenwhen
including group, season, gender, age, testing time, and
wake time.
Conclusion:
These data are the first to link light exposure
and thePIPR inSAD.We speculate that low light levels in
SAD trigger downstream changes inmood and behavior,
and that the link between light andSADmay bemediated
by thePIPR.
Support:
The studywas supported byMH096119.
LBA4
1:25pm – 1:40pm
Efficacy andSafety of Oral ADX-N05
for theTreatment of ExcessiveDaytime
Sleepiness inAdultswithNarcolepsy: Results
of aRandomized, Double-Blind, Placebo-
ControlledTrial
Black J
1,6
, Swick T
2
, FeldmanN
3
, Doekel R
4
, KhayrallahM
5
,
BreamG
5
, Ruoff C
6
1
JazzPharmaceuticals, Inc., PaloAlto, CA, USA,
2
Neurology andSleepMedicineConsultants of Houston,
University of Texas-HoustonSchool of Medicine, Houston,
TX, USA,
3
St. PetersburgSleepDisordersCenter at Palms
of PasadenaHospital, St. Petersburg, FL, USA,
4
Sleep
DisordersCenter ofAlabama, Birmingham,AL, USA,
5
Aerial BioPharma, Morrisville, NC, USA,
6
StanfordSleep
MedicineCenter, RedwoodCity, CA, USA
Introduction:
ADX-N05 (N05) is a uniquewake-promoting
agent with dopaminergic and noradrenergic activity that
is being evaluated for the treatment of excessivedaytime
sleepiness (EDS) in adultswith narcolepsy.
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