European Psychiatry - Volume 33 - March 2016

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24th European Congress of Psychiatry / European Psychiatry 33S (2016) S116–S348 S211
Methods To prove our hypothesis we used a rodent model with
90 malewistar-ratswhichwere housed individually in single cages.
Water, 3 alcohol-solutions (5%, 10% and 20%) and food were offered
to the animals ad libitum for one year (4 bottle paradigm), whereas
control groups got 4 bottles filled with water. The continuous
alcohol consumption of the animals was interrupted by sched-
uled alcohol-deprivation-phases. During the animal trial amanifest
alcohol dependencewas induced. The blood and tissues, obtained at
the end of the trial, were analysed using direct bisulfite-sequencing
(methylation status) and Elisa (alpha-MSH protein levels).
Results and discussion The group of alcohol dependent animals
showed an altered methylations status of the POMC-gene-
promoter and altered levels of alpha-MSH compared to the control
group. These findings are in line with our previous results showing
a significant correlation between symptoms of alcohol craving and
POMC-promoter methylation. These new data confirm our results
from humane materials and clarify the meaning of alpha-MSH for
craving in alcohol dependence.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
EW279
Characterizing rare mis-sense
variations of CACNA1I identified in a
Swedish schizophrenia cohort
J. Pan ∗, A. Allen , L. huang , D. Daez
Broad Institute of Harvard and MIT, Stanley Center for Psychiatric
Research, Cambridge, USA
∗ Corresponding author.
CACNA1I (hCaV3.3) encodes the 1 pore-forming subunit of human
voltage-gated T-type calcium channels. CaV3.3 is expressed in a
limited subset of neurons including GABAergic neurons of the
thalamic reticular nucleus (TRN) where they support oscilla-
tory activity essential for sleep spindle generation. CACNA1I is
implicated in schizophrenia risk by emerging genetics including
genome-wide association studies (PGC, 2014), and exome sequenc-
ing of trio samples (Gulsuner et al., 2013). In order to understand
the impact of disease-associated sequence variation on the function
of CaV3.3, we set out to analyze a complete set of rare mis-sense
coding variations in CACNA1I in a Swedish cohort, including 15 vari-
ations identified in patients, 20 identified in control subjects, and
23 in both. We established a heterologous expression systemof iso-
genic cell lines, each carrying single-copy inducible cDNA variants
of hCaV3.3, and evaluated their functional impact on channel func-
tion by electrophysiology, calcium imaging, and biochemistry. We
found at least five coding variations impaired overall channel pro-
tein abundance, as well as whole cell current density. In addition,
we identified hCaV3.3 variants with altered voltage-dependence of
channel activation and inactivation. Overall, we found that reduced
calcium influx through hCaV3.3 is associatedwith the group of vari-
ants identified in patients, compared to those in both patients and
controls. Our findings suggest that patient-specific rare variations
of CACNA1I may influence channel-dependent functions, including
rebound bursting in TRN neurons, with potential implications for
schizophrenia pathophysiology.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
EW280
Polymorphism neuropeptide receptor
gene S (NPSR1) and sleep disturbances
V. Gafarov ∗, M. Voevoda , E. Gromova , V. Maximov ,
D. Panov , I. Gagulin , A. Gafarova
1 FSBI Institute of Internal and Preventive Medicine, Collaborative
Laboratory of cardiovascular disease epidemiology, Novosibirsk,
Russia
2 FSBI Institute of Internal and Preventive Medicine, Laboratory of
molecular and genetic study, Novosibirsk, Russia
∗ Corresponding author.
Objective To study the association gene of candidate NPSR1
rs324981with sleep disorders in the open population of men 45–64
years of Novosibirsk.
Materials and methods The study of the association candidate
gene polymorphisms with sleep disorders was carried out during
the examination of a random representative sample of men 45–69
years (n = 1770). The response rate was 61%. The median age is
56.5 year. Every 12 a man was selected for genotyping (n = 147). To
assess the level of sleep was used a questionnaire which was filled
with self-test. Statistical analysis was performed using SPSS-11.5.
Results The level of sleep disorders in the male population of
45–64 yearswas 79.9%. The frequency of homozygous C/C genotype
of neuropeptide S (gene NPSR1 rs324981) was 19.4%, T/T geno-
type occurs in 27.8%, C/T genotype −52.8%. Men dominated the T
allele of −54.2%, and the C allele −45.8% growth trend Fnd dissat-
isfaction with the quality of their sleep among men. Men T-allele
carriers, most evaluated their sleep as “satisfactory” in 69% of cases,
( 2 = 15,713 df = 8, P < 0.05).
Conclusion Association found men carrier T-allele of neuro-
peptide S (gene NPSR1 rs324981), a sleep disorder.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
EW281
Methylomic changes in individuals
exposed in utero to diethylstilbestrol
F. Rivollier∗, O. Kebir , B. Chaumette , M.O. Krebs
Sainte-Anne Hospital, Service Hospitalo-Universitaire, Paris, France
∗ Corresponding author.
Background In the Western world, more than 2 million people
were exposed in utero to diethylstilbestrol. In exposed individ-
uals and in their descendants, several adverse outcomes have been
linked to such exposure, like cancers, genital malformations and,
less consistently, psychiatric disorders. Disruption of epigenetic
homeostasis was proposed as the molecular substratum of this
environmental factor but was not fully proven.
Methods We selected 69 siblings from 30 families. In each fam-
ily, at least one sibling was exposed in utero to diethylstilbestrol.
We analyzed DNAmethylation using HumanMethylation 450 DNA
Analysis BeadChip® . We performed a methylome-wide associa-
tion analysis searching for specific methylation changes in exposed
versus unexposed individuals. Secondary, we compared exposed
individuals with and without genital malformation, and with and
without psychosis.
Results No differentially methylated regions were identified
between exposed and unexposed individuals. Yet, our analyses
showed that exposed individuals with genital or psychotic abnor-
malities have several specific differentially methylated regions
compared with exposed individuals without complication. These
CpGs were located in genes relevant for cancer (ADAMTS9), genital
abnormalities (HOOK2) and psychiatric diseases (ZFP57).
Conclusions In utero exposure to diethylstilbestrol is not associ-
ated with changes in methylation profiles. In exposed individuals
though, specific traits are associated with methylomic modifica-
tions encompassing genomic regions, mostly involved in cancer
and neurodevelopment, leading to heterogeneous consequences.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.