European Psychiatry - Volume 41 - April 2017

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S56 25th European Congress of Psychiatry / European Psychiatry 41S (2017) S53–S68
W011
Inflammation and pruning may
inform risk to psychiatric disorders.
lessons from large genetic data
C. Crisafulli
University of Messina, department of biomedical and dental science
and morphofunctional images, Messina, Italy
Background It’s known that psychiatric disorders are caused
to either environmental and genetics factors. Through the years
several hypotheses were tested and many genes were screened
for association, resulting in a huge amount of data available for
the scientific community. Despite that, the molecular mechanics
behind psychiatric disorders remains largely unknown. Traditional
association studies may be not enough to pinpoint the molecu-
lar underpinnings of psychiatric disorder. We tried to applying
a methodology that investigates molecular-pathway-analysis that
takes into account several genes per time, clustered in consistent
molecular groups andmay successfully capture the signal of a num-
ber of genetic variations with a small single effect on the disease.
This approach might reveal more of the molecular basis of psychi-
atric disorders.
Methods i)We collected data on studies available in literature for
the studied disorder (e.g. Schizophrenia, Bipolar Disorder);ii)We
extracted a pool of genes that are likely involved with the dis-
ease;iii)We used these genes as starting point to map molecular
cascades function-linked. The molecular cascades are then ana-
lyzed and pathways and sub-pathways, possibly involved with
them, are identified and tested for association.
Results/discussion We obtained interesting results. In particular,
signals of enrichment (association) were obtained multiple times
on the molecular pathway associated with the pruning activity and
inflammation. Molecular mechanics related to neuronal pruning
were focused as a major and new hypothesis for the pathophysi-
ology of psychiatric disorders and the role of inflammatory events
has been extensively investigated in psychiatry. intersting, inflam-
matory mechanics in the brain may also play a role in neuronal
pruning during the early development of CNS.
Disclosure of interest The author has not supplied his declaration
of competing interest.
W012
Combined analysis of large genetic
samples: new statistical approaches
improve gene discovery
O. Smeland ∗, Y. Wang , K. Kauppi , O. Frei , A.M. Dale ,
O.A. Andreassen
1 Oslo university hospital, norment- kg jebsen centre for psychosis
research- institute of clinical medicine, Oslo, Norway
2 University of Oslo, NORMENT- KG Jebsen centre for psychosis
research- institute of clinical medicine, Oslo, Norway
3 University of California- San Diego, department of radiology, San
Diego, USA
∗ Corresponding author.
Introduction Cognitive dysfunction is recognized as a core fea-
ture of schizophrenia and is considered an important predictor
of functional outcomes. Despite this, current treatment strategies
largely fail to ameliorate these cognitive impairments. In order
to develop more efficient treatment strategies, a better under-
standing of the pathogenesis of cognitive dysfunction is needed.
Accumulating evidence indicates that genetic risk of schizophrenia
contributes to cognitive dysfunction. However, the precise genetic
variants jointly influencing schizophrenia and cognitive function
remain to be determined.
Aims Here, we aimed to identify gene loci shared between
schizophrenia and general cognitive function, a phenotype that
captures the shared variation in performance across several cog-
nitive domains.
Methods Using a Bayesian statistical framework, we compared
genome-wide association study (GWAS) data on schizophrenia
from the Psychiatric Genomics Consortiumcohort (n = 79,757) with
GWAS data on general cognitive function from the CHARGE Con-
sortium (n = 53,949). By conditioning the false discovery rate (FDR)
on shared associations, this statistical approach increases power to
detect gene loci.
Results We observed substantial polygenetic overlap between
schizophrenia and general cognitive function, which replicated
across independent schizophrenia sub-studies. Using the condi-
tional FDR approach we increased discovery of gene loci and
identified 13 loci shared between schizophrenia and general cog-
nitive function. The majority of these loci (11/13) shows opposite
directions of allelic effects in the phenotypes, in line with pre-
vious genetic studies and the observed cognitive dysfunction in
schizophrenia.
Conclusions Our study extends the current understanding of the
genetic etiology influencing schizophrenia and general cognitive
function by identifying shared gene loci between the phenotypes.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
W013
RNA sequencing in bipolar disorder:
from long non-coding to circular rnas
J. Luykx ∗, F. Giuliani , J. Veldink , R. Kahn
1 UMC Utrecht, brain center rudolf magnus- neurogenetics unit,
Utrecht, The Netherlands
2 UMCU, translational neuroscience, Utrecht, Netherlands Antilles
3 UMCU, neurology, Utrecht, Netherlands Antilles
4 UMCU, psychiatry, Utrecht, Netherlands Antilles
∗ Corresponding author.
Bipolar disorder (BPD) is a highly debilitating psychiatric disor-
der. The underlying molecular mechanisms of BPD remain largely
unknown. Studies targeting postmortem brain tissues of BPD
patients have identified very few consistently replicated differ-
ences in the expression levels of protein-coding RNAs across
different areas of the brain. Since differential expression of the
human genome produces a wide spectrum of protein-coding and
noncoding RNAs, we hypothesized that major molecular deficits
associated with BPD could reflect dysregulation of multiple classes
of RNA. To test this hypothesis, we obtained postmortem human
medial frontal gyrus tissue from BPD patients and healthy con-
trols (n = 16). To survey the implication of both protein-coding and
long non-coding RNAs (lncRNAs) in BPD, we then performed RNA
sequencing, PCR validation and replication experiments adopting a
case-control design. Thirty-six genes and fifteen lncRNA transcripts
not previously implicated in BPD were detected as differentially
expressed (FDR < 0.1). Functional analyses identified enrichments
of angiogenesis, vascular system development and histone H3-K4
demethylation. In addition, we report extensive alternative splic-
ing defects in the brains of BPD subjects compared to controls.
Finally, we describe for the first time a large reservoir of circular
RNAs (circRNAs) that populate the medial frontal gyrus and report
significantly altered levels of two circular transcripts (cNEBL and
cEPHA3) from the NEBL and EPHA3 loci in BPD. Our findings may
not only contribute to gain insight into the pathophysiology of BPD
but may be tested in the near future as potential biomarkers for
diagnostics.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.