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In general
Disorders
are dealt with (biologically) on
three levels
PSY 210
Lecture 12: The Biological Basis
of Mental Illness
Genetic Contributions to
Depression
Depression
Major
depressive disorder (unipolar):
Lengthy, uninterrupted periods of
depressed mood
Manic depressive disorder (bipolar):
Cycling between periods of elevated mood
(mania) and depression
While sharing the common feature of
depression, these are unique and
separate disorders
Brain Structure and Function in
Depression
Happy
moods are associated with activity
in the left frontal lobes
Depression is correlated with increased
right frontal lobe activity and decreased
left frontal lobe activity
Left hemisphere damage due to stroke
and other medical causes is associated
with depression
Structural brain problems
Chemical brain problems
Genetic studies
Concordance
rate between identical twins
is about 40 – 60%
Adoption studies support a role for
genetics in depression
Families with depressed members also
have very high rates of anxiety disorders
Biochemistry of Depression
Possibly due to problems in the HypothalamicPituitary-Adrenal Axis, depressed people show
elevated:
growth hormone levels
thyroid hormone levels
Stress hormone leves
• cortisol levels
• Glucocorticoid levels
Depression Is Associated with
Abnormal Sleep Patterns
Neurotransmitters and
Depression
History:
Depressed people:
fall asleep faster
enter REM earlier
spend little time in
Stage 3 or 4
awaken frequently
Reserpine was found to deplete available monoamines
and produces profound depression
What is a monoamine?
• Noradrenaline, dopamine, serotonin, etc….
What about “modern”
antidepressants?
How do antidepressants work?
Antidepressant medications act on monoamines
Monoamine Oxidase Inhibitors (MAOIs)
• MAOIs suppress MAO, which breaks down monoamines
• Bad side effects and dangerous dietary restrictions
Selective serotonin reuptake inhibitors (SSRIs)
inhibit the reuptake of serotonin
Tricyclic antidepressants
• Name comes from chemical structure- contains a 3 ring
carbon chain
• Inhibit the reuptake of serotonin and norepinephrine
• Also acts on histamine and acetylcholine
Leads to unwanted side effects
Led to the desire to develop drugs that only worked in very specific
ways
Other
drugs are currently under
development
Chemical Theories of
Depression
Monoamine theory of Depression
First started as the catecholamine theory of
depression
• Noradrenaline and dopamine depletion led to
depression (Reserpine)
• Cocaine should help with this though, as it increases
catecholamines
Now it is generally called the monoamine theory
• Depression is due to a deficiency in one or another of
three monoamines: serotonin, noradrenaline, or
dopamine
Serotonin-noradrenaline reuptake inhibitors
(SNRIs)
Chemical Theories of
Depression
Receptor
Sensitivity Theory of Depression
Switches the focus from the neurotransmitters
to the receptors
Blocking of receptors with antidepressants
takes place immediately
• Leads to an immediate increase in monoamines
• Patients don’t report benefits for weeks
But it does not lessen depression
• Minimizes the importance of serotonin
Prozac, zoloft, lexapro
These don’t work better than tricyclics, but are safer
drugs
Thus, it is not the immediate chemical
changes that help the patient, but longer
lasting (secondary) changes that may help the
patient
Schizophrenia
Positive
Symptoms
Delusions
Hallucinations
Disorganized speech
Disorganized behavior
Negative
© Najlah Feanny/CORBIS
What about Schizophrenia?
Symptoms
Social withdrawal
Mood disturbance
John Nash
Schizophrenia May Have
Several Outcomes
Prevalence of Schizophrenia
Affects 0.5–1% of the world’s population
2.5 million Americans have schizophrenia
Men and women are equally likely to be
diagnosed to schizophrenia
Current thought is that it is a group of related
disorders and not just one disorder
Age at diagnosis:
Structural Brain Problems
• Tissue loss
• Frontal cortex,
anterior temporal
lobes,
hypothalamus have
all been found to be
smaller as well
Very rarely diagnosed in children as young as 6 years
of age
Mode: 18–25
Diagnoses may occur as late as a person’s 40s
Structural Brain Problems
• Enlarged ventricles
• Shrunken Hippocampus
Structural Brain Problems
cell bodies in a control
participant are arranged neatly
Hippocampus cell bodies in a participant
diagnosed with schizophrenia appear
relatively disorganized
Courtesy Arnold B Scheibel,
University of California, Los Angeles
Hippocampus
A Comparison of Auditory
Hallucinations and Listening to
Real Voices
Biochemical causes of
Schizophrenia
dopamine hypothesis
•
– overabundance of
dopamine
– Leads to
overactivity
– May be the basis
for hallucinations
and delusions
Problems With a Dopamine
Hypothesis
25% of patients do not respond to dopamine antagonists
Atypical antipsychotic medications (clozapine) act
primarily on neurotransmitters other than dopamine
Drugs change dopamine activity immediately, but patient
may not improve for weeks
PCP produces symptoms similar to schizophrenia by
blocking the NMDA glutamate receptor
Prolactin levels in schizophrenics are normal
Dopamine inhibits prolactin production
Support for the Dopamine
Hypothesis
Drugs
that increase Dopamine activity
in Schizophrenics intensifies
symptoms
Drugs that block dopamine receptors
lessen symptoms
Seems to work for the hallucinations
and delusions
Does not help with social withdrawal
symptoms
Genetic Causes of Schizophrenia
• Heritability Index of 40 60%
• For fraternal twins only
10 - 20% chance
• Children of a
Schizophrenic patient: 1417% chance
Psychological Causes of
Schizophrenia
early
childhood experiences
Neglect
Physical abuse
Sexual abuse
Causes of Schizophrenia:
Putting it all together
Diathesis-Stress Model
predisposition for schizophrenia
triggers when person encounters great
stresses
Other Causes of
Schizophrenia
Sociocultural
8 times more schizophrenics among
poor people
poverty or social stress trigger
schizophrenia or schizophrenics can't
hold jobs which leads to poverty status
Treatments for Schizophrenia
In
Insulin Coma Therapy
Give
patients Insulin
Aids in the digestion of glucose
(sugar)
When enough insulin was given,
patients went into a coma
1-10% mortality rate
Main treatment used through the 60’s
the past
Most schizophrenics locked in
asylums
Given Sedatives
Mid 1930’s: Insulin Coma Therapy
Treatments for Schizophrenia
Late
1950’s
Started with antihistamines
• Mainly sedated schizophrenics
• Led to the discovery of thorazine
Thorazine
Calmed
out
How did it work?
Clozapine
Evidence from reserpine again…
• Similarities between thorazine and reserpine
Atypical Antipsychotics
patients without knocking them
Knew reserpine was linked to catecholamine depletion
Both thorazine and reserpine led to Parkinsonian like
symptoms – tardive dyskinesia
• Once Parkinson’s was found to be linked to
dopamine levels, it was assumed that thorazine
worked on Dopamine
Amphetamines led to schizophrenic like
behaviors and work primarily on dopamine
circuits
Treatments for Schizophrenia
Magnetic
stimulation of the brain
seems to reduce hallucinations
Before Treatment
After Treatment
Works in 30-50% of the patients that did not
respond to other antipsychotics
Blocks dopamine receptors and serotonin
receptors