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24th European Congress of Psychiatry / European Psychiatry 33S (2016) S18–S55

S53

Towards personalized pharmacotherapy for

suicide prevention across the lifespan

S110

Using genomics to predict

antidepressant response in suicidal

depressed children

Maya Amitai (MD)

1 , 2 , 3

, Alan Apter (MD)

1 , 2 ,

1

Department of Psychological Medicine, Schneider Children’s

Medical Center of Israel, Petach Tikva, Israel

2

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3

The Ruhman Family Laboratory for Research on the Neurobiology of

Stress, Department of Neurobiology, Weizmann Institute of Science,

Rehovot, Israel

Corresponding author.

Background

Depression and anxiety disorders are among the

most common childhood psychiatric disorders. Selective serotonin

reuptake inhibitors (SSRIs) are generally considered first-line treat-

ment for both depression and anxiety in this age group. However,

it has been reported that 30%–40% of all patients who receive a

sufficient dose and duration of treatment fail to respond. More-

over, SSRI use is frequently associated with serious adverse events

(SAE), including activation symptoms, manic switch and increased

suicidal behavior. These are particularly relevant in pediatric popu-

lations because of concerns about the suicide threat of SSRIs,

resulting in a black-boxwarning. Currently there is noway of know-

ing in advance who of the patients will respond. Identification of

biomarkers that would be early predictors of response and of the

occurrence of SAE could help to maximize the benefit–risk ratio for

the use of SSRIs, and speed up the matching of treatment to patient.

The main objective of this project is therefore to identify and vali-

date biomarkers predicting response and SAE in depressed children

and adolescents, thus improving treatment, enabling the develop-

ment of novel diagnostic tests and suggest novel therapeutic targets

for future related drug development.

Methods

As a preliminary pilot, we already obtained blood sam-

ples from 80 depressed and anxious children and adolescents over

the last year before, during and after eight weeks of fluoxetine (FLU)

therapy. Genetic and epigenetic samples were collected from all

participants. The patients were treated with FLU 20–40mg/day for

8weeks. Clinical responsewasmeasuredwith several scales includ-

ing the Children’s Depression Rating Scale–Revised (CDRS-R), the

Beck Depression Inventory (BDI) and the Screen for Child Anxiety

Related Emotional Disorders (SCARED).

Results

The participant’s age ranged from 6 to 18 (14.12

±

2.30)

years. The overall response rate was 56%. Ten percent responded

with SAE. Regarding Pharmacogenetics, The 5-HTTLPR ss geno-

type was associated with a poorer clinical response with regard to

depressive symptoms as well with fewer reports of agitation com-

pared to the ll genotype. Regarding immunemeasures, we analyzed

cytokine levels from 41 children. Plasma concentrations of TNF- ,

IL-6 and IL-1 were measured by enzyme linked immunosor-

bent assays (ELISA) before and after FLU treatment. Antidepressant

treatment significantly reduced TNF- levels (

P

= 0.037), with no

significant changes in the levels of IL-6 and IL-1 . All three

pro-inflammatory cytokines were significantly (

P

< 0.05) higher in

SSRI-refractory than SSRI-responsive patients, i.e.: higher levels of

TNF- , IL-6 and IL-1 might predict non-response to fluoxetine

treatment in children.

Future plans

Out of the study sample we selected 13 remit-

ters and 13 non-responders and 10 children with SAE (activation

symptoms, manic/hypomanic switch, increased suicidality), and

analyzed expression profiles in peripheral blood at admission

and after 8 weeks of treatment using illumine Truseq technique.

Hopefully, we shall find significant differences in miRNA profiles

between the different groups which may serve as biomarkers indi-

cating AD treatment response and SAE. The differentially regulated

miRNA’s can be studied in depth in the future in animal models in

order to support the hypothesis that they may be involved in the

AD mechanism.

Disclosure of interest

The authors have not supplied their decla-

ration of competing interest.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.926

S111

Large-scale suicide prevention by

pharmacological treatment of mood

disorders

E. Isometsa

University of Helsinki, Department of Psychiatry, Helsinki, Finland

Introduction

In psychological autopsy studies, at least half of sui-

cides have suffered from depressive or bipolar disorders at time of

death. Improving access to care and provision of evidence-based

pharmacotherapies can be important preventive measures.

Objectives

To examine suicide risk and pharmacoepidemiology

in mood disorders; evidence for efficacy of pharmacotherapies in

mood disorders and in preventing suicidal behaviour in them, and

limitations to effectiveness of treatment due to problems of adher-

ence.

Aims

To evaluate potentials for suicide prevention in mood

disorders by improved access to treatment, improved quality of

treatment provision, improved adherence, or by specific pharma-

cotherapies.

Methods

Selective review of literature.

Results

Risk of suicide death and attempts in mood disorders

clusters intomajor depressive andmixed illness episodes, and time

spent in them is a major determinant of risk, but direct evidence for

preventive effects of effective pharmacotherapies remains limited.

Observational and randomized studies indicate lithium treatment

to reduce risk of suicide deaths and attempts. Ecological evidence

from Europe shows increasing sales of antidepressants to con-

sistently associate with declining regional suicide rates. Forensic

chemical studies still findmajority suicides negative for antidepres-

sants. Poor adherence is a central problem in treatment provision.

Conclusions

Positive impact of increase in pharmacotherapy

provision in the last few decades on suicide mortality remains

uncertain. Lithium is the pharmacological agent with best evi-

dence for preventive utility, but underused. Providing treatments

for those at risk, improving quality and continuity of treatment,

and integrating them with psychosocial approaches is likely to be

beneficial for suicide prevention.

Disclosure of interest

The author has not supplied his declaration

of competing interest.

http://dx.doi.org/10.1016/j.eurpsy.2016.01.927

S112

Brain imaging biomarkers in

personalizing pharmacotherapy of

suicidal depressed patients

J.J. Mann

Columbia University, New York, NY, USA

Background

New knowledge has emerged about decision-

making, mood regulation, social distortions and learning that is

relevant for the diathesis for suicidal behavior. All four domains

have identified underlying neural circuits and for decision-making

and mood regulation also specific neurotransmitter systems.

Methods

We have conducted PET studies of the serotonergic sys-

temandCSF studies of the serotonin, norepinephrine anddopamine

neurotransmitter systems in patients surviving suicide attempts

to determine whether they have neurotransmitter abnormalities

that resemble those found in the brain after suicide. We found