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Lecture 5

2LA2 Lecture Notes - Lecture 5: Transferase, Main Source, Mania

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What are the two main categories of depression?
1) Major Depressive Disorder (MDD): characterized by a persistent unpleasant mood,
depressed mood or the loss of interest/pleasure in nearly all activities.
2) Persistent Depressive Disorder (PDD): dysthymia, characterized by chronic mild
depressive symptoms. Depressed mood for most of the day, more days than not, for at
least 2 years.
What is anhedonia?
Depressive mood and inability to experience pleasure, a symptom of depression.
What are the DSM criteria for Major Depressive Disorder?
Presence of 5 or more of the following symptoms during a 2-week period, must
represent a change from previous functioning:
Anhedonia, feelings of worthlessness or excessive guilt, decreased concentration,
psychomotor agitation or retardation, insomnia or hypersomnia, decreased libido,
change in weight or appetite, thoughts of death and suicidal ideation.
What are the risk factors for depression?
Childhood emotional, physical or sexual abuses
Prior episode of depression
Family history of depressive disorder
Lack of social support
Stressful life event
Current substance abuse
Economic difficulties
What is the etiology of depression?
Multifactorial and has a dynamic interplay amongst: genetic predisposition,
environment, life history, development and biological challenges.
Does heritability or environment contribute more to depression?
Hereditability for depression has been estimated form twin studies as 31-42%
Environment contribution is 58-67%
How does the polymorphism of serotonin transporter gene increase or decrease the risk of
Polymorphism can give rise to long and short alleles, therefore different combinations
of genes can arise. The short alleles slow down the synthesis of the serotonin
transporter leading to a dysregulation of serotonin, and this process has been
implicated in depression.
What is Brain Derived Neurotropic Factors (BDNF) and is it increased or decreased in MDD?
Growth factor important for survival and maturation of brain cells during development.
It activates DNA binding factors that stimulate gene transcription of genes involved in
serotonin function.
People with MDD have lower levels of BDNF.
What are the genes that code for BDNF? And what gene increases the chance for depression?
Val ad Met alleles i gees ode for BDNF, the Met alleles irease a perso’s hae
for depression.
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Why is the hippocampus significant in depression, what effect does the Met allele have on it?
Met alleles do the following: small hippocampus at birth, hippocampal hypo activity at
rest, hippocampal hyper activity during learning, poor hippocampus dependent
Hippocampus is significant because it modulates cognitive aspects of depression such as
memory impairments and feelings of hopelessness, guilt, doom and sucicidiality.
Do we diagnose people simply by looking at low levels of BDNF?
No, we diagnose them with DSM 5 symptoms. It is important to look at BDNF to figure
out what is the best way to increase BDNF levels.
What does the neurobiological theory suggest in terms of depression?
MDD is caused by a deficiency or dysregulation in the CNS concentration of
1) Where can you find neurotransmitter
acetylcholine (Ach) in the brain?
2) What is the effect on the brain?
3) What does under/over activity
1) High concentrations in basal ganglia and
motor cortex.
2) Can be excitatory and inhibitory,
depending on area of brain.
3) Under activity implicates in Alzheimer
1) Where can you find neurotransmitter
dopamine (DA) in the brain?
2) What is the effect on the brain?
3) What does under/over activity
1) Substantia nigra and ventral segmental
area of midbrain, derived from tyrosine.
2) Usually excitatory. Involved in motivation,
thought and emotional regulation.
3) Over activity thought to be involved in
schizophrenia and other psychotic disorders.
1) Where can you find neurotransmitter
norepinephrine (NE) and epinephrine
(E) in the brain?
2) What is the effect on the brain?
3) What does under/over activity
1) Locus ceruleus in brain stem.
2) Can be excitatory or inhibitory, depending
on area of brain.
3) Under activity thought to be involved in
some depressions.
1) Where can you find neurotransmitter
serotonin (5-HT) in the brain?
2) What is the effect on the brain?
3) What does under/over activity
1) Raphe uleus i rai stethat’s ai
function is to release serotonin to rest of
2) Involved in regulation of attention and
complex cognitive functions.
3) Under activity thought to be involved in
some depressions and OCD.
1) Where can you find neurotransmitter
y-aminobutyric acid (GABA),
glutamate and glycine in the brain?
1) No single main source.
2) GABA and glycine are usually inhibitory;
glutamate excitatory.
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2) What is the effect on the brain?
3) What does under/over activity
3) Implicated in anxiety disorders.
Where are neurotransmitters usually stored?
In vesicles in the presynaptic axonal terminal.
What process released the neurotransmitters into the synaptic cleft?
When an excitatory neurotransmitter binds to the postsynaptic receptor what is the
Results in the opening of an ion channel, such as the sodium channel.
What do presynaptic receptors function as?
Function in a negative feedback manner to inhibit further release of neurotransmitters.
What are the three ways of removing the neurotransmitter from the synaptic cleft?
Be taken back up into the neuron in process called reuptake, diffuse out of the synaptic
cleft or be broken down by enzymes into inactive substances or metabolites.
What does the biogenic amine hypothesis suggest?
Suggests that decreased levels of serotonin and norepinephrine in the synaptic cleft,
due to either decreased presynaptic release or decreased postsynaptic sensitivity, is the
underlying pathologic process in depression.
What contradicts the biogenic amine hypothesis and supports genetic and environmental?
We know that when serotonin levels are depleted experimentally in humans by oral
treatment by decreasing the level of tryptophan (precursor to serotonin) healthy
idiiduals that do’t’ hae a history of MDD tend not to show mood changes.
While idiiduals ho hae suessfully ee treated ith SSRI’s ill relapse ito
What does decreased and increased dopamine activity indicate?
Decreased activity in depression and increased activity in mania.
Wh do patiets ith Pakiso’s disease hae a high feue of depessio?
Parkiso’s disease has lower rates of dopamine production in substantia nigra.
How does neurotransmitter alteration in MDD and bipolar disorders affect the volume of the
Reduction in gray matter volume in prefrontal cortex, decreased activity because of
decrease in serotonin and norepinephrine and alterations in dopamine. Also a decrease
in BDNF in prefrontal cortex.
This decrease in neurotransmitter activity leads to decrease in neuronal volume since
pathays are’t eig used, therefore desity of these pathays dereases ad there is
What does the white matter composed of versus gray matter of the brain?
White matter: primarily myelinated axons.
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