Genetic basis of depression

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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