The Drug Revolution for
Mental Health
Medicine for Madness
Demonic Possession
St. Zenobius
exorcises devils
(seen fleeing from
the mouths of the
possessed)
A hole in the head:
Trepannation
Benjamin Rush
(1745-1813)
Treated mentally ill
at Pennsylvannia
hospital
Madness as disease
Used talk therapy
Humane treatment
Holistic approach
Phillipe Pinel
(1745-1826)
“Treatise on
Insanity” 1791
Removed chains
from mental ill
patients at Paris
asylum (1792)
Pinel freeing patients
Dorothea Lynde Dix
(1802-1887)
Found mentally ill
housed in jails (MA)
Helped found
hospitals in 15
states & Canada
Humane care
Supervised nursing
corp: US Civil War
Early Treatment
The spinning
chair
One of Rush’s
invention
Treatments not
very effective
Early
th
20
century treatments
Insulin coma
Lobotomy
First generation “shock” treatment
Restraints
Restrictions
Warehousing
State hospitals growing every year
Deinstitutionalization
KW 6-9
Mental health movement
Move patients to less restrictive
environments (out of state hospitals)
Follow up with community mental health
Monitor continued drug treatment
Patient rights
Change in commitment laws
Drug can Modify
KW 6-5
Mood Disorders
Mood Disorders
characterized by emotional extremes
Major Depressive Disorder
no apparent reason,
experiences two or more weeks of depressed
moods,
feelings of worthlessness, and
diminished interest or pleasure in most
activities
Depression
 Major Depressive Disorder
 Defined-long-term sadness and helplessness
 Demographics
 Observed more often in women than men
 Peak frequency between 25 and 44
 About 19% of all people suffer a bout of depression at least
once in their lives
 Genetics
 Depression does have a genetic link
 Gene has not been located
Gender Differences in
Depression
10%
Percentage
depressed 8
Females
6
4
2
Males
0
12-17 18-24 25-34 35-44 45-54 55-64 65-74 75+
Age in Years
Mood Disorders- Suicide
Suicides per 70
100,000 people 60
50
The higher suicide rate
among men greatly
increases in late
adulthood
40
30
20
10
0
15-24 25-34 35-44 45-44 55-64 65-74 75-84 85+
Males
Females
Depression
 Reactive
 Related to traumatic life event
 Can be triggered by an event (ex: death of a loved one, birth of a
child, etc)
 Endogenous
Source from within
More likely to be related to neurochemical differences
Depression
Physiology of Depression
Two Conclusions
Mood depends on the effects of a combination of
transmitters
Different depressed people have somewhat different
transmitter abnormalities
Video
Mood DisordersDepression
Brain
chemistry
Cognition
Mood
Altering any one
component of
the chemistrycognition-mood
circuit can alter
the others
Depression
 Drug Treatments
Antidepressants
Tricyclics-prevent reuptake of serotonin or
norepinephrine/epinephrine
MAO Inhibitors-block MAO from breaking down
serotonin and norepinephrine/epinephrine
SSRI’s-Selective Serotonin Reuptake inhibitor:
inhibits reuptake of serotonin
Routes of action of antidepressants
Tricyclics block the reuptake of dopamine, norepinephrine, or serotonin.
SSRIs specifically block the reuptake of serotonin.
MAOIs block the enzyme MAO, which converts dopamine, norepinephrine, or
serotonin into inactive chemicals.
Serotonin and Depression
KW 6-11
Prozac
MDMA Casues Cell Damage
MDMA Changes the
density of serotonin
axons in monkeys
Normal brain on left
Brain on right 18
months following
treatment
Depression: Other treatments
 ECT
 Applied
every other day for two weeks
 Muscle relaxants and anesthetics minimize
discomfort
 Memory loss can be a side-effect (limited if
shock is given to right hemisphere only
 Altered Sleep Patterns
 Treat patient like someone with difficulty
adjusting to changing time zones
Biomedical Therapies
Electroconvulsive Therapy
Seasonal Affective Disorder
Defined-depression that regularly recurs in a particular season
Usually treated by bright light therapy
Mood Disorders
Manic Episode
a mood disorder marked by a hyperactive,
wildly optimistic state
Bipolar Disorder
alternates between the hopelessness of
depression and the overexcited state of mania
formerly called manic-depressive disorder
Bipolar Disorder
Defined-alternate between mania and depression
Demographics
May last only days or for a year or more
1% of people have a mild case at some time in life
Average age of onset is early 20’s
Genetics
Concordance rate is .50
No specific gene has been identified
Mood Disorders-Bipolar
PET scans show that brain energy consumption
rises and falls with emotional swings
Depressed state
Manic state
Depressed state
Bipolar Disorder
Treatments
Lithium
Stabilizes mood
Mechanism unknown
Side effect: toxicity
Anticonvulsant drugs (like Depakote)
Mechanism of action on cortex (lower activity)
Schizophrenia
Definitions
Schizophrenia
literal translation “split mind”
a group of severe disorders
characterized by:
disorganized and delusional thinking
disturbed perceptions
Schizophrenia
Symptoms
Delusions
false beliefs, often of persecution or
grandeur, that may accompany
psychotic disorders
Hallucinations
false perceptual experiences such as seeing
something without any external visual
stimulus
Prevalence
Schizophrenia affects about 1% of the population and
range in severity.
Occurs in all parts of the world, but is 10 to 100 times
more common in the United States and Europe than
in third-world countries.
More common in men than in women by a ration of
about 7 to 5.
More severe and earlier age of onset for men (early
20’s versus late 20).
Likelihood increases as the age of the father
increases.
Characteristics of Schizophrenia
Characteristics
Deteriorating ability to function
Accompanied by delusions, hallucinations, thought disorder,
movement disorder and inappropriate emotional expression
Behavioral Symptoms
Positive Symptoms-behavior that are present that should
be absent
Delusions, hallucinations, thought disorders
Negative Symptoms-behavior that is absent that should be
present
Weak social interactions, emotional expression,
speech, and working memory
Probabilities of developing schizophrenia
The closer the genetic relationship to someone with schizophrenia, the higher
the probability of developing it oneself.
Schizophrenia and Genetics
Genetics
Concordance rate is 50%
However, genes are not the only influence
A gene has not been located for schizophrenia
Hypotheses of Causation in Schizophrenia
 Neurodevelopmental
 Either genes or difficulties early in life impair brain development in
ways that lead to schizophrenic-like symptoms in early adulthood
 Dopamine Hypothesis-Excess dopamine activity causes behavioral
changes associated with schizophrenia
 Supported by drug treatments that target dopamine
 Glutamate Hypothesis-the problem is deficient glutamate activity
Neurodevelopmental
The neurodevelopmental hypothesis suggests
abnormalities in the prenatal or neonatal
development of the nervous system.
Leads to subtle abnormalities of brain anatomy and
major abnormalities in behavior.
Abnormalities could result from genetics, difficulty
during birth, or a combination of both.
Causation
Supporting evidence for the neurodevelopmental
hypothesis includes:
Several kinds of prenatal or neonatal difficulties
are linked to later schizophrenia.
People with schizophrenia have minor brain
abnormalities that originate early in life.
Abnormalities of early development could impair
behavior in adulthood.
Prenatal Risk Factors
Prenatal risk factors increasing the likelihood of
schizophrenia include:
Poor nutrition of the mother during pregnancy.
Premature birth.
Low birth weight.
Complications during delivery.
Head injuries in early childhood are also linked to
increased incidence of schizophrenia.
Season of Birth
Certain viral infections may be an alternative or
supplement genetic influences.
The seasoned-of-birth effect refers to the tendency
for people born in winter to have a slightly (5% to 8%)
greater probability of developing schizophrenia.
More pronounced in latitudes far from the equator.
Might be explained by complications of delivery,
nutritional factors, or increased likelihood of
viral infections
Schizophrenia and Brain
Schizophrenia is associated with mild brain
abnormalities:
Strongest deficits found in the left temporal and
frontal lobe of the cortex.
Larger than normal ventricles.
 Especially common in those with complications
during birth.
Areas that mature slowly such as the dorsolateral
prefrontal cortex.
Schizophrenics have deficits in working memory.
Normal Twin
Schizophrenic Twin
MRI Scans of Schizophrenia
CBF in Schizophrenia
Treatment
Antipsychotic/neuroleptic drugs are
drugs that tend to relieve schizophrenia
and similar conditions.
Chlorpromazine (thorazine) is a drug
used to treat schizophrenia that relieves
the positve symptoms of schizophrenia.
Relief usually experienced 2-3 weeks after
taking the drug, which must be taken
indefinitely.
Schizophrenia Treatment
Antipsychotic Drugs-All block postsynaptic dopamine receptors
First Generation Antipsychotics (FGA’s)
Phenothiazines-chlorpromazine
Butyrophenones-haloperidol
Dopamine and Psychosis
KW 6-10
Antipsychotics
Dopamine hypothesis
The dopamine hypothesis of schizophrenia suggests
that schizophrenia results from excess activity at
dopamine synapses in certain areas of the brain.
Substance-induced psychotic disorder is
characterized by hallucinations and delusions
resulting from repeated large doses of
amphetamines, methamphetamines, or cocaine.
Each prolongs activity of dopamine at the
synapse, providing further evidence for dopamine
hypothesis.
Pathways affected
The mesolimbocortical system is a set of neurons
that project from the midbrain tegmentum to the
limbic system.
Site where drugs that block dopamine synapses
produce their benefits.
Drugs also block dopamine in the mesostriatal
system, which project to the basal ganglia.
Result is tardive dyskinesia, characterized by
tremors and other involuntary movements.
Fig. 15-20, p. 479
SGA’s
Second-generation antipsychotics (atypical
antipsychotics) are a class of drugs used to treat
schizophrenia but seldom produce movement
problems.
Examples: clozapine, risperidone.
More effective at treating the negative symptoms and
are now more widely used.
Have less effect on dopamine D2 receptors and
more strongly antagonize serotonin type 5-HT2
receptors.
TGA’s?
Third Generation Antipsychotics.
Abilify® (aripiprazole)
Act on both dopamine and serotonin.
Regulates, rather than blocks, dopamine.
May help both positive and negative
symptoms.
Side effects: restlessness, constipation,
sleepiness, involuntary movement.
Schizophrenia Conclusions
Schizophrenia cannot be explained by a
single gene or single transmitter.
Dopamine and glutamate may play important
roles in schizophrenia to different degrees in
different people.
Schizophrenia involves multiple genes and
abnormalities in dopamine, glutamate,
serotonin and GABA.