genetic basis of depression
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Genetics of Genetics of DepressionDepression
Discussion OutlineDiscussion Outline Discussion OutlineDiscussion Outline
Depression Facts
Finding the Genetic Links
Twin Studies
The Depression Gene
Future Prospects
Beat Depression
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Quick Summary Quick Summary Quick Summary Quick Summary
Depression has a strong Genetic Influence
Tends to runs in families
Many Other factors are also involved
Genetic understanding is very important:
To design new drugs and therapies
To understand type of depression completely
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Depressive DisorderDepressive Disorder
Clinical Depression: Life threatening Mood
Disorder
Effects a person’s whole life
More common in Women and Children
Anyone might be at RISK ..
Getting help is Seriously important
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Depression Is the Inability to Construct a Future ..Depression Is the Inability to Construct a Future ..Depression Is the Inability to Construct a Future ..Depression Is the Inability to Construct a Future ..
Depression Statistics 2010Depression Statistics 2010Depression Statistics 2010Depression Statistics 2010
The 4th leading cause of disease burden in world
(WHO)
Leading cause of mental disability in U.S (NIMH)
15 % depressed patients commit Suicide
In UK, ¼ college students suffer depression (Times
Online)
By 2020, depression will be the 2nd most common
health problem in the world (WHO)
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Common Types of DepressionCommon Types of Depression
Major Depressive Disorder (MDD) Dysthymic Disorder Unipolar Depression Bipolar Disorder OR Mania Cyclothymic Disorder Substance-Induced Mood Disorder Seasonal Affective Disorder (SAD) Postpartum Depression
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Warning Signs !!!Warning Signs !!!
Sadness, Anxiety Loss of Interest Hopelessness Loss of Energy Worthlessness Thoughts of Suicide Restlessness, Irritability Difficulty in Decision Making Problems in Eating, Sleeping and
Concentration
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What Causes Depression?What Causes Depression?
Biological Causes Psychological Causes Environment Medicines Life Events
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Depression CycleDepression CycleDepression CycleDepression Cycle
Is Depression Inherited?
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Some Important Considerations …Some Important Considerations …
Genes determine our susceptibility
to different medical conditions:
What if a family member has depression
history?
How genetics influences depression?
How to treat depression on genetic
basis?
Twins StudiesTwins Studies
Identical & Fraternal Twins
Confirmation of Genetic Link
Genetic Risk is 40%
Other Factors 60%
Is there a Depression Gene?Is there a Depression Gene?
The 5-HTT OR SLC6A4 Gene (Caspi et. al., 2003)
Produces protein which is involved in Serotonin reuptake
Two form of gene; Long & Short
Same protein but difference is in Serotonin Regulation
Inheriting a Susceptible gene is not a Definite Clue..
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Serotonin Biosynthesis PathwaySerotonin Biosynthesis Pathway
A Neurotransmitter
Regulates anger, sleep,
appetite and mood
Synthesized by Tryptophan
Serotonin Deficiency causes
Depression
Defects in Tph2 gene cause
Depression
The Serotonin being released from the presynaptic cell and binding to the receptors on the postsynaptic cell. 5-HTT encodes the protein labeled "reuptake transporter”.
Short vs. Long Version Short vs. Long Version
Depression Patients have impaired 5-
HTT genes
Short form is more Vulnerable (Caspi,
et. al., 2003)
L/L are more Resistant
(High 5-HTT production)
L/S OR S/S are more Susceptible
(Low 5-HTT production)
Genotype Allele Frequency
L/L 32 %
L/S 49 %
S/S 19 %
Ref: Dunedin Multidisciplinary Health and Development Study; New Zealand (September 2003)
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* * Polymorphism lies in Promoter Length Polymorphism lies in Promoter Length (OMIM, 2003)(OMIM, 2003)* * Ins/Del of Ins/Del of 44 bp 44 bp close to gene’s transcription site close to gene’s transcription site (Caspi et. al., 2003) (Caspi et. al., 2003) * * Polymorphism causes decreased gene expression (Few 5-HTT produced) Polymorphism causes decreased gene expression (Few 5-HTT produced) (Caspi et. al., 2003)(Caspi et. al., 2003)** Mutations within coding region of 5-HTT are not responsible for Depression Mutations within coding region of 5-HTT are not responsible for Depression (Di Bella et. al., 1996)(Di Bella et. al., 1996)
* * Polymorphism lies in Promoter Length Polymorphism lies in Promoter Length (OMIM, 2003)(OMIM, 2003)* * Ins/Del of Ins/Del of 44 bp 44 bp close to gene’s transcription site close to gene’s transcription site (Caspi et. al., 2003) (Caspi et. al., 2003) * * Polymorphism causes decreased gene expression (Few 5-HTT produced) Polymorphism causes decreased gene expression (Few 5-HTT produced) (Caspi et. al., 2003)(Caspi et. al., 2003)** Mutations within coding region of 5-HTT are not responsible for Depression Mutations within coding region of 5-HTT are not responsible for Depression (Di Bella et. al., 1996)(Di Bella et. al., 1996)
Source: Source: NCBI Map ViewerNCBI Map ViewerHomo sapiens, Homo sapiens, Chromosome: Chromosome: 17, 17, LocationLocation: 17q11.1_q12 , : 17q11.1_q12 , QueryQuery 5- 5-
HTTHTT
Source: Source: NCBI Map ViewerNCBI Map ViewerHomo sapiens, Homo sapiens, Chromosome: Chromosome: 17, 17, LocationLocation: 17q11.1_q12 , : 17q11.1_q12 , QueryQuery 5- 5-
HTTHTT
Location of 5-HTT Gene on Chromosome 17
Custom-made AntidepressantsCustom-made Antidepressants
Make neurotransmitters more available to the
brain
Improve mood, sleep, appetite, and concentration
Depression genes differ from person-to-person
Response to treatment is also different
More research work is needed to be done….
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Future Insights …Future Insights …Future Insights …Future Insights …
Identif ication of Depression genes wil l help:
To understand genetic behavior of depression
Understand how depression runs in families
Genetic Counseling
Mental health professionals
Design new therapies
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Live A Depression Free Life …Live A Depression Free Life …Live A Depression Free Life …Live A Depression Free Life …
Tips to Beat Depression..Tips to Beat Depression..Tips to Beat Depression..Tips to Beat Depression..
Seek Medical Treatment
Exercise, Jog, Deep Breaths
Avoid Antisocial Behavior
Avoid Negativity
Healthy Diet
Care for Yourself
Healthy Atmosphere
Help Others
Sleep Enough
Talk to Friends and Family
Adopt Creative Activities
Be Around Optimistic People
Do What You Enjoy
Take A Break
Laughing More
Don't Be Afraid to Cry
Build Up Your Self-Confidence
Make A List of Your Priorities
Avoid Stimulants
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