European Psychiatry - Volume 41 - April 2017

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S164 25th European Congress of Psychiatry / European Psychiatry 41S (2017) S106–S169
specifically responding to a certain drug. Despite decades of
efforts though, pharmacogenetics appears to be still in its
infancy.
Aim A clearer understanding of the pharmacodynamics and
pharmacokinetics events in combination with the genetic and epi-
genetic controls of cells and molecular cascade must inform the
future of personalised medicine.
Objectives To systematically review the current cutting edge
knowledge about pharmacognetics in the search for the next
groundbreaking biological key events that may provide the keys
to future treatments.
Methods The major online databases are systematically searched
with common keywords by two independent researchers and
conflicting findings are solved during regular meetings dedicated
to the topic in object. Manual searching of single bibliographies is
also put in place.
Results Genes belonging to the serotoningeric, dopaminergic,
glutamatergic and GABAergic systems are classic candidates for
pharmacogenetics whose role was not confirmed by GWAS analy-
ses, which, on the other hand, identified genes related to molecular
pathways not associated with direct target of drugs used for the
treatment of depression.
Conclusion Both hypothesis driven candidate genetic investiga-
tions and GWAS analyses have been conducted so far, leading
to the identification of a handful of potential good candidates,
but the replication rate of the positive association findings lags
behind expectations. The current knowledge about the phar-
macodyncamic and pharmacokinetic genetic determinants of
antidepressant response is critically analysed and new candidates
are presented discussed.
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
EW0176
A molecular pathway analysis informs
the genetic risk for arrhythmia during
antipsychotic treatment
E.K. Fischer ∗, H. Dyrby Andersen , M. Braun Jepsen , A. Drago
1 Psykiatrisk Forskningsenhed Vest, Forskningsenheden, Herning,
Denmark
2 Region Psykiatri Vest, Herning, Denmark
∗ Corresponding author.
Background Arrhythmia is a potentially fatal side effect of
antipsychotics. A biologic predictive tool to prevent it is missing.
Aim Identification of a genetic profile at risk for antipsychotic
induced arrhythmia.
Objective Identifying a molecular pathway enriched for antipsy-
chotic induced QT-modifications.
Methods Seven hundred and sixty-five SKZ individuals, M = 556,
age = 40.93 ± 11.03 were included. QT-variation was a phase-
specific created variable. A nested mixed regression served in R for
clinical and molecular pathway analyses. Plink served for genetic
analyses. Quality checking was standard, inflation factor was con-
trolled by lambda values.
Results Quetiapine and Perphenazine were associated with
QT variation (P = 0.002; Estimate = 5.79 and P = 5.67e-06; Esti-
mate = 8.96 respectively). No other significant association was
detected. No inflation was detected. Axon guidance and Collagen
biosynthesis were associated with QT variation at a con-
servative (adjusted) P value < 0.01.
Conclusions Two molecular pathways were identified as possi-
bly involved in QT modifications during antispsychotic treatment
in SKZ patients. Previous evidence supports a role of the same path-
ways in cardiac disorders nteraction of specific SNPs with the
drugs will be focus of further research.
Table 1 Molecular pathways enriched in association with QT
modifications.
ID Description Gene Ratio BgRatio P-value P.adjust Qvalue
422475 Axon guidance 19/135 292/6750 4.6e–06 0.0022 0.0021
1650814 Collagen
biosynthesis
and modifying
enzymes
8/135 59/6750 1.9e–05 0.0047 0.0044
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
References
[1] Fukuda K, et H, et al. Cardiac Innervation and Sudden Cardiac
Death. Circ Res 2015;116:2005–19.
[2] Lazzerini PE, et al. Connective tissue diseases and cardiac
rhythm disorders: an overview. Autoimmun Rev 2006;5:
306–13 [2005.11.002].
EW0177
A molecular pathway analysis stresses
the role of inflammation towards
cognition in Schizophrenia
E.K. Fischer ∗, C. Holm , M. Christensen , A. Drago
1 Psykiatrisk Forskningsenhed Vest, Forskningsenheden, Herning,
Denmark
2 Via University College, Herning, Denmark
∗ Corresponding author.
Background Cognitive processes are impaired in Schizophrenia
(SKZ). The nature of such impairment escapes definition.
Aim Identification of a genetic profile at risk of cognitive impair-
ment.
Object Identifying a molecular pathways enriched for mutations
associated with cognitive impairment.
Methods Seven hundred and sixty-five individuals from the
CATIE, M = 556, mean age = 40.93± 11.03 were included. Verbal
memory was outcome. R and Plink served for the analyses. Inflation
factor was controlled by lambda values. Input for the pathway anal-
ysis were SNPs associated with outcome (P < 0.05) genomewide.
Results Gender (male, P = 2.34e–05;t = –4.26) and years of educa-
tion (P = 1.57e–03;t = 6.502) were associated with verbal memory.
Inflammation and oxidation were associated with outcome
dj P < 0.01).
Conclusions Being male and poorly educated were associated
with poorer verbal memory. Inflammation and the arachidonic acid
pathway were enriched inmutations associated with poorer verbal
memory. This finding is in line with previous reports
Table 1 Pathways enriched in association with verbal memory.
Description GeneRatio BgRatio P value P.adjust
Synthesis of
Leukotrienes
5/105 17/6750 4.42E–06 0.0009
Arachidonic acid
metabolism
7/105 45/6750 5.03E–06 0.0009
Glutathione
synthesis and
recycling
4/105 11/6750 1.68E–05 0.0021
Disclosure of interest The authors have not supplied their decla-
ration of competing interest.
References
[1] Hoffman DR, et al. Toward optimizing vision and cognition
in term infants by dietary docosahexaenoic and arachidonic
acid supplementation: a review of randomized controlled trials.
Prostaglandins Leukot Essent Fatty Acids 2009;81:151–8.