1. Psychopharmacogenomics in Child & Adolescent Psychiatry
Esmaeil Shahsavand Ananloo, MD, PhD
Department of Genomic Psychiatry and Behavioral genomics (DGPBG)
Roozbeh Hospital, School of Medicine
Tehran University of Medical Sciences (TUMS)
2nd. Congress of Pharmacotherapy in Child and Adolescent Psychiatrydolescent Psychiatry

2. CONTENTS I- Problem: Clinical Phenotype-Based Diagnosis
II- A Few Solutions
II-1) Phenomics-Based Diagnosis
II-2) Endophenotype-Based Diagnosis
II-3) Biomarker-Based Diagnosis
III- Psychopharmacogenomics
IV- Psychopharmacogenomics of ADHD; As an Example
Summary

3. I- Problem: Clinical Phenotype-Based Diagnosis
Current treatment strategies rely:
Rely on symptom-based diagnosis (DSM and ICD)
Based on symptom clusters rather than the underlying EtioPathophysiology
Clinical Phenotype: A Serious Problem
Because: No Pathognomonic Symptom !

4. I- Problem: Clinical Phenotype-Based Diagnosis
Overlaps: ED
OCD
ADHD BD
ASD
Anxiety
...

5. I- Problem: Clinical Phenotype-Based Diagnosis
Problem of Validity !
Problem of Reliability !
Problem of Diagnostic Stability !
Problem of Co-morbidity !
Problem of Treatment !

6. I- Problem: Clinical Phenotype-Based Diagnosis
Drugs: absence of predictive factors for efficacy.
Physicians:
Rely on their own experience
With a considerable element of trial and error prescribing

7. II- A Few Solutions: II-1) Phenomics-based Diagnosis
One-Level Approach (Clinical)
Multi-Level Approach

8. II- A Few Solutions: II-1) Phenomics-based Diagnosis
Phenome:
Represents the sum total of the organism’s phenotypic traits:
Transcriptome
Proteomics
Metabolomics
.....
Change in response to genetic mutation and environmental influences.
Phenomics:
An area of biology concerned with the study and measurement of Phenomes.

9. II- A Few Solutions: II-1) Phenomics-based Diagnosis
Research Team of the Future
CNP Team 9

10. II- A Few Solutions: II-1) Phenomics-based Diagnosis10

11. II- A Few Solutions: II-2) EndoPhenotype-based Diagnosis
Is a Genetic Epidemiology term
Is more stable Phenotype
With a clear Genetic connection
In Psychiatric Genetics:
To bridge the gap between high-level symptom presentation &
low-level genetic variability, such as: SNPs, CNVs

12. II- A Few Solutions: II-2) EndoPhenotype-based Diagnosis

13. II- A Few Solutions: II-3) Biomarker-based Diagnosis
Biomarkers (Biological markers) are defined as traits that are specific to particular conditions.
Biomarkers (Better Diagnosis)
Genomic
Epigenomic
Imaging
Biochemical
Anatomical
…..
Identify clearly aetiopathological factors
Carter et al, 2012; Stober et al, 2009

14. III- Pychopharmacogenetics
The Best Drug
Best Effect on Phenomics Levels
Best Effect on Endophenotypes
Best Effect on Biomarkers

15. Novel Discipline: Pychopharmacogenetics
III- Pychopharmacogenetics
Antipsychotics, antidepressants, anxiolytics and mood stabilising agents have all been discovered at the beginning of the 2nd. half of the 20th. century.
However, serious limitations are:
Relatively low response rate
Unpredictibility of the response
Deleterious side effects (quality of life / poor compliance)
A new step in the development of better treatments
Improving the design and synthesis drug molecules
Considering the genotype as a possible reason for good, poor or no responding to drugs.
Novel Discipline: Pychopharmacogenetics

16. III- Pychopharmacogenetics
Specifically relates to the genetic understanding of the variability in response to psychiatry drugs.
Use of genetic markers as part of a physician’s decision-making criteria.
Reduces the reliance on trial and error prescribing.
Ultimately lead to more effective medicines and improved healthcare for patients.

17. maximal chance of positive response minimal risk of side effects
III- Pychopharmacogenetics
Drugs with:
maximal chance of positive response
minimal risk of side effects
Giving:
the right drug
at the right dose
to the right patient
at the right time

18. CVD; DM; Cancer SCZ; BD; Autism III- Pychopharmacogenetics
deCODE genetics, Inc.
Is a biopharmaceutical company based in Iceland.
Was founded in 1996.
To identify human genes associated with common diseases using population studies.
Apply the knowledge gained to guide the development of candidate drugs.

19. ADHD; A few examples IV- Psychopharmacogenetics of ADHD; As an Example
Gene (Chr.)
Marker
Drug Response
Reference
MAO-A (Chr. X)
VNTR (4-repeat allele of MAOA 30 bp)
Response to methylphenidate
Grevet et al., 2007
NET
G1287A
(A/A genotype)
Yanget al., 2004
DRD4
VNTR (48-bp variant)
Cheon et al., 2007
DRD5
CA(n) microsatellite marker
Thapar et al., 2007

20. ADHD; A few examples IV- Psychopharmacogenetics of ADHD; As an Example
Gene (Chr.)
Marker
Drug Response
Reference
DAT1
VNTR (9-repeat allele in 3’UTR)
Non-Response to methylphenidate
Stein et al., 2002
VNTR (10-repeat allele in 3’UTR)
Response to methylphenidate
Kirleyet al. (2003

21. I- Problem: Clinical Phenotype-Based Diagnosis II- A Few Solutions
Summary
I- Problem: Clinical Phenotype-Based Diagnosis
II- A Few Solutions
II-1) Phenomics-Based Diagnosis
II-2) Endophenotype-Based Diagnosis
II-3) Biomarker-Based Diagnosis
III- Psychopharmacogenomics
IV- Psychopharmacogenomics of ADHD; As an Example

22. Thanks Indeed