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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.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.396

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

(hCa

V

3.3) encodes the 1 pore-forming subunit of human

voltage-gated T-type calcium channels. Ca

V

3.3 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 Ca

V

3.3, 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 hCa

V

3.3, 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 hCa

V

3.3 variants with altered voltage-dependence of

channel activation and inactivation. Overall, we found that reduced

calcium influx through hCa

V

3.3 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.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.397

EW280

Polymorphism neuropeptide receptor

gene S (NPSR1) and sleep disturbances

V. Gafarov

1 ,

, M. Voevoda

2

, E. Gromova

1

, V. Maximov

2

,

D. Panov

1

, I. Gagulin

1

, A. Gafarova

1

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.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.398

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.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.399