Genetic Factors in the onset of depression
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Transcript of Genetic Factors in the onset of depression
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Involvement of Genetic and Environmental
Factors in the Onset of Depression
Toshitaka Nabeshima & Hyoung-Chun Kim Journal of Experimental Neurobiology
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Penny Chatzistylianou
Dora Boukoura
Emmanouela Zoulia
Dennis Patriarcheas
Venetia Giourou
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Introduction
● Modern society includes various stressors● Adolescents have little resistance to stress factors ● On their way to adulthood from puberty, adolescents are
prone to mental disorders______________________________________________________● Bipolar disorder: Alternation between depression symptoms
& symptoms of mania● Schizophrenia: Hallucinations or delusions (positive) &
withdrawal or introversion (negative)
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Risk factors in puberty:
1. Social non-comformity2. Withdrawal3. Bullying/teasing4. Bereavement of close relatives5. Being raised by step-parents6. Drug or alcohol abuse
> 10-15% prevalence, expected to be ranked second for life expectancy loss> In the background of suicides
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CAUSES OF DEPRESSION
● Patients suffering from cancer ● Chronic pain ( diabetes or other chronic diseases) ● Drugs (anti-hypertensive drugs , hormone
drugs ,anti-ucler drugs , psychotropic drugs immunomodulatory drugs and anti-tuberculosis drugs)
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ΜΟΝΟΑΜΙΝΕ HYPOTHESIS
Rauwolfia serpentina:root from the homonymous tree-used as anti-hypertensive and sedative drugSide effect: Depression-like symptomsReserpine: component of this root-decreases monoamines(neurotransmitters)
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Iprioniazid: improves the mood (inhibits the action of the enzymes that deplete monamines)+imipramine (action that leads to iprioniazid-like results)
Depression is related to dysfunction of nerves in which monamines are
neurotransmitters
Monoamine hypothesis is however rejected
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Brain-derived neurotrophic factor hypothesis
● loss of BDNF involves in the pathophysiology of depression
● decreased BDNF levels are associated with depression
● antidepressants increase BDNF levels● controversial studies about the relationship
between BDNF levels and mood
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Receptor Hypothesis
● Hyperactivity of monoamine receptors● Excessive neurotransmission in patients
with depression● Suppression of monoamine release● Decrease in free monoamine results in not
proper neurotransmission
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Genetic factors in the onset of depression
● With immediate family members, depression familial incidence is 1,5-3 times higher
● Identical twins: when one twin develops depression, the other has a probability of 25-93%
● Studies at post-mortem brains have shown ABCB1, HDAC6, etc
● These results imply that there is a gene-related/genetic basis, regarding depression.
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Antidepressants’ effects
● Repeated administration leads in a reduction in the number of serotonine and noradrenaline β receptors and weakens neurotransmission
● Moderation of monoaminergic nervous system’s hyperactivity
● Modulation of receptors sensitivity
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Disrupted in schizophrenia 1(DISC1) defects
● The gene disrupted in schizophrenia was shorter in patients compared to healthy ones.The protein product of the DISC1 gene was later found to be necessary for neural development.
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EXPERIMENT
Scientists extracted 14-day-old mouse embryos from the mothers womb and subjected them to a treatment that would silence the DISC1 gene in the prefrontal cortex using siRNA.The embryos were then returned to the womb to continue gestation.
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These mice had :● delayed neural development ● undeveloped neural network formation ● diminished attention and cognition in pre-
pulse inhibition testing.Thus when a specific gene is prevented from working ,mice present abnormal behavior.
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MAGE-D1 Gene Defect
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Neurodevelopmental disorders: the TWO-HIT hypothesis
● child receives first ‘hit’(G and/or E) is predisposed to
occur disorders and will do so if there is a 2nd hit (E)
● study: mice with G + low stress : abnormal behavior # wild-
type mice no abnormal behavior in low stress
● epigenetics ( studies changes in gene action that occur
without changes in DNA sequencing) also involves in
disorders occurance
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Conclusion● Disadvantaged environments boost the onset of
depression (parent neglect/abuse, bullying/teasing, overworking of employees)
● However, even with genetic predisposition, resistance to the illness is possible
● It is also possible to suffer from depression without genetic factors being present
● The key to the problem is to create a healthy and supportive environment to gain resistance to stress