what is the relation between psychiatry and genetics? (basic)

1. ISMAIL SADEK
Lecturer of psychiatry
Faculty of medicine

2. • Determine the sequence of the 3 billion nucleotides
that make up human DNA
• Characterize variability in the genome
• Identify all the genes in human DNA
• The Era of Genomic Medicine:
– Improve prediction of drug efficacy or toxicity
– Improve the diagnosis of disease
– Earlier detection of genetic predisposition to
disease
Human Genome Project

3. DNA is Information
• DNA
• A, T, G, C
• Codon
• Gene
• Chromosome
• Genome
• ENGLISH
• Abcdefg….xyz
• Word
• Sentence
• Chapter
• Book

4. Mutation: difference in the DNA code that occurs
in less than 1% of population
Often associated with rare diseases
Cystic fibrosis, sickle cell anemia, Huntington’s disease
Polymorphism: difference in the DNA code that
occurs in more than 1% of the population
A single polymorphism is less likely to be the main cause
of a disease
Polymorphisms often have no visible clinical impact

5. Pronounced “snip”
Single base pair difference in the DNA sequence
Over 2 million SNPs in the human genome
Other polymorphisms:
Insertion/deletion polymorphisms
Gene duplications
Gene deletions

6. Alleles = different
DNA sequences at a
locus
Codon 389 β1-AR
Arg (0.75)
Gly (0.25)
Genotype = pair
of alleles a person
has at a region of
the chromosome
Codon 389 β1-AR
Arg389Arg
Arg389Gly
Gly389Gly

7. Population genetics:
Family studies
Twin studies
Adoption studies
Epidemiologic studies:
Genetic cohorts
Molecular methods
Linkage studies
Association studies
Expression studies
(epigenetic
analyses)
Animal models

8. Population studies
Molecular methods
Candidate genes
(polymorphisms)
biological hypotheses
Epidemiologic analyses Genetic Risk

9. MentalMental
IllnessIllness
&&
GeneticsGenetics
SchizophreniSchizophreni
aa Bipolar DisorderBipolar Disorder
Alzheimer’sAlzheimer’s
DiseaseDisease
DepressionDepression

11. Alzheimer’s Disease Age-related
Forgets entire experiences Forgets part of an experience
Is gradually unable to care for
self
Is usually able to care for self
Rarely remembers later Often remembers later
Is gradually unable to follow
written/spoken directions
Is usually able to follow
written/spoken directions

12. Alzheimer dementia
●
Main symptoms: Progressive deterioration of
cognitive abilities, agitation, hallucinations.
●
Neurodegenerative disease, EC: neuritic plaque, IC:
neurofibrillar filaments, beta-amiloyd
●
Familial AD (5%): mendelian transmission, dominant,
early manifestation: APP (amyloid precursor protein),
presenilin1, presenilin 2
●
Sporadic AD (95%): polygenic, late-onset:
apolipoprotein E e4 allele risk factor, GWAS replicated
●
APP gene on chromosome 21- association with
Down-trisomy

13. • Risk genes increase the likelihood of
developing a disease, but do not guarantee
it will happen.
• Scientists have so far identified one
Alzheimer risk gene called apoliprotein E-
e4 (APOE-e4).

14. • Deterministic genes directly cause a
disease, guaranteeing that anyone who
inherits them will develop the disorder.
• Rare genes that directly cause Alzheimer’s
have been found in only a few hundred
extended families worldwide.

15. • A gene on chromosome 19 involved in
making ApoE, a substance that helps
carry cholesterol in the bloodstream.
• The APOE e4 gene is considered a
“risk factor” gene for AD and appears
to influence the age of onset of the
diesease.

16. • Genetic tests are available for both APOE-
e4 and the rare genes that directly cause
Alzheimer’s.
• Health professionals do not currently
recommend routine genetic testing for
Alzheimer’s disease.

18. *The serotonin transporter gene is linked to depression.
*It controls two parts of the brain: amygdala and cingulate
*Two types of this gene: the long and short version
*Those with two copies of the long version show better
connectivity between the amygdala and cingulate
http://www.nimh.nih.gov/science-news/2005/depression-gene-may-
weaken-mood-regulating-circuit.shtml

19. *Identical twins have identical genetic material.
-If twins are raised together and one twin develops
clinical depression, the other twin develops clinical depression
76% of the time.
-If twins are raised apart and one twin develops clinical
depression, the other twin develops clinical depression 67% of
the time
*Shown to go through families
*If a parent or sibling has had a major depression, the person
may be 1.5 to 3 times more likely to develop depression

21. • Research
• Twin Studies
• Genes
– GRK-3 gene, chromosome
22
– FAT-1 gene, chromosome 4
– AY070435 gene (Slynar),
chromosome 12
• Thought to be on 18 & 21
• Then 1, 6, 7, & 10, 22
• 11 & X-Chromosome
• Polymorphisms

22. Genetics of mood disorders
●
Highly prevalent disorders (MDD~15%, BD~6%)
●
Familial transmission straightforward in BD (h2: 0.8,
MZ: 65%, DZ: 14%), moderate in MDD (h2: 0.39,
MZ:50%, DZ:18%)
●
GWAS studies yielded a few significant markers in BD
with only 1 gene in concert with linkage results
(CACNA1C, OR=1.14), again explaining only 2% of
heritability variance
●
No markers reached significance in MDD, and the
main candidate gene (SLC6A4) association was
dismissed by recent meta-analyses

24. Schizophrenia
●
Main symptoms: delusions, hallucinations,
disorganized thoughts and behavior
●
Familial transmission is straightforward (heritability:
0.8, MZ twins: 48-59%, DZ twins: 16% concordance)
●
Referred to as the totally unsuccessful example of
linkage and association studies
●
GWAS studies did not replicate previously implicated
candidate genes, and significant markers only explain
3% of the heritability -> “missing heritability”

25. Heredity

26. • Researchers have found possible gene defects
linked to schizophrenia on the following
chromosomes:
1, 6, 8, 10, 13, 18, 22, and the X
chromosome
• Polygenic: caused by a combination of gene
defects
• Genes and Environment?