Genetic Factors in the onset of depression

Involvement of Genetic and Environmental

Factors in the Onset of Depression

Toshitaka Nabeshima & Hyoung-Chun Kim Journal of Experimental Neurobiology

Penny Chatzistylianou

Dora Boukoura

Emmanouela Zoulia

Dennis Patriarcheas

Venetia Giourou

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)

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

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)

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)

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

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

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

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.

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

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.

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.

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.

MAGE-D1 Gene Defect

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

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