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25th European Congress of Psychiatry / European Psychiatry 41S (2017) S53–S68


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


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.


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.


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.


Combined analysis of large genetic

samples: new statistical approaches

improve gene discovery

O. Smeland

1 ,

, Y. Wang


, K. Kauppi


, O. Frei


, A.M. Dale



O.A. Andreassen



Oslo university hospital, norment- kg jebsen centre for psychosis

research- institute of clinical medicine, Oslo, Norway


University of Oslo, NORMENT- KG Jebsen centre for psychosis

research- institute of clinical medicine, Oslo, Norway


University of California- San Diego, department of radiology, San

Diego, USA

Corresponding author.


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.


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.


Using a Bayesian statistical framework, we compared

genome-wide association study (GWAS) data on schizophrenia

from the Psychiatric Genomics Consortiumcohort (


= 79,757) with

GWAS data on general cognitive function from the CHARGE Con-

sortium (


= 53,949). By conditioning the false discovery rate (FDR)

on shared associations, this statistical approach increases power to

detect gene loci.


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



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.


RNA sequencing in bipolar disorder:

from long non-coding to circular rnas

J. Luykx

1 ,

, F. Giuliani


, J. Veldink


, R. Kahn



UMC Utrecht, brain center rudolf magnus- neurogenetics unit,

Utrecht, The Netherlands


UMCU, translational neuroscience, Utrecht, Netherlands Antilles


UMCU, neurology, Utrecht, Netherlands Antilles


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 (


= 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


Disclosure of interest

The authors have not supplied their decla-

ration of competing interest.