Mood Disorders
Major (unipolar) depression
Probably more than 1 type
Endogenous vs Reactive
Bipolar disorder
Major (or
“unipolar”)Depression
l sadness, feel helpless,
hopeless, worthless
l no energy, apathetic,
nothing matters
l can’t make decisions,
complete tasks
l lose appetite for food &
sex, disordered sleep, move & talk slowly
l suicidal thoughts or actions
Bipolar Disorder
l a.k.a. manic-depressive
disorder
l over time goes from 1 mood
extreme to the other
l increased energy, activity
& speech
l decreased need for sleep;
may be irritable
l unrealistic view of their
capabilities, delusional
Genetic Factors
l Mood disorders tend to run
in families(~10x more likely if you have affected relatives )
l 10-20% of the relatives of a
depressed individual also suffer from the disorder
l 25% with major depression
and 50% with bipolar disorder have depressed parents
Genetic Factors
l About 70% concordance in
identical twins vs about 13% in fraternal twins for major depression; about 80%
for bipolar disorder
l Adopted depressed children
more likely to have depressed biological parents
l Stronger genetic link for
early, severe depression, and for females
l Interacts with environmental
factors
Monoamine Theory
of Depression
l Normal mood depends on
adequate levels of monoamine activity in brain.
l Levels too low à depression
l Levels too highà euphoria, mania
l Used to focus on NE, now its
clear that serotonin (5HT) also critical
Tricyclic
Antidepressants
l 3 best known:
» imipramine (Tofranil)
» amitriptyline (Elavil)
» desipramine (Norpramin)
l prevent reuptake of 5HT, NE
& DA
l But have some annoying &
dangerous side effects
MAO Inhibitors
l Example: phenelzine (Nardil)
l Inhibit action of MAO, an
enzyme which breaks down 5HT, DA and
NE, therefore making transmitters more available
l But: dangerous interactions
with diet & stimulant drugs
Selective
Serotonin Reuptake Inhibitors (SSRIs)
l fluoxetine (Prozac), sertraline (Zoloft), paroxetine
(Paxil),fluvoxamine (Luvox), citalopram (Celexa)
l Block reuptake of 5HT
l same effectiveness but fewer
side effects and risks; patients much more willing to take SSRIs
Atypical
Antidepressants
l Don’t fit previous
categories
l E.g. bupropion (Wellbutrin),
venlaxafine (Effexor), nefazodone (Serzone)
l Various mechanisms of action
The Monoamine
Theory
l Availability is not enough -
drugs all increase availability immediately but don’t become clinically
effective for a few weeks
l Hypothesis: improved mood
depends on a slower adaptation of CNS to increased availability (“down-regulation
of receptors” and altered release of transmitter)
l Different people may have
different monoamine imbalances
Circadian Changes
in Depression
l Temp cycle advanced and
sleep abnormal: early REM & more REM despite early morning awakening
l Either REM deprivation or
total sleep deprivation can relieve depression
l Antidepressants drugs also
decrease REM sleep
l SAD associated with phase
delayed cycles
Other Brain
Changes
l Excess activation of HPA
responses
l High levels of cortisol which
are not reduced by dexamethasone injections
l Decreased left prefrontal
(“happy”) activity
l Right hemisphere more active
l Individuals with left hem
damage often depressed
l Those with right hem damage
may become manic
l Electroconvulsive shock
therapy limited to the right hemisphere can be effective, with little effect on
memory
Another Biological
Factor:
Borna Virus
l Borna disease causes
bipolar-like behavior in horses.
l May be passed to humans
l Studies revealed Borna in
very few normal mood individuals, but is present in ~30% of severely depressed.
May also increase your risk of other psychiatric problems.
Bipolar Disorder
l Drug of choice has been
lithium carbonate (e.g. Eskalith)
l Takes 7-10 days to act, 3 or
more weeks for maximal effect, but is good at preventing future attacks
Biological Basis
of Schizophrenia
Characteristics of
Schizophrenia
z
Hallucinations
z
Delusions
z
Disordered
thought
z
Inappropriate
emotion
z
Often
bizarre behavior
z
“positive
symptoms”
z
Decreased
social interaction
z
Normal
emotion lost
z
Speech
often decreased
z
“negative
symptoms”
Characteristics
z
Incidence
a little over 1% of the population
z
Usual
symptom onset in early adulthood; early 20’s for men, late 20’s for women
z
All
“schizophrenics” do not show the same behaviors - may be several different
types of schizophrenia
Genetics of
Schizophrenia
z
Schizo.
runs in families - you have increased
risk if you have blood relatives with schizo
z
Overall
concordance in identical twins is ~45-50%, in fraternal twins its ~15-17%
z
Identical
twins with same handedness have a 92% concordance rate, that of those with
opposite handedness is 25%
z
6/51
kids born to nonschizo member of identical
twin pair, 5/36 kids born to twins with schizophrenia (17.4% vs
16.8%)(not true of fraternals)(suggests the unaffected twins still have “bad
gene(s)”)
Genetics of
Schizophrenia
z
Adoptees
with schizophrenia are more likely to have schizophrenic biological parents
& relatives than adoptive parents & relatives.
z
A
child of a schizophrenic parent raised by a normal couple is more likely to
show schizophrenia than a child of normal parents who has a schizophrenic
adopted parent.
z
63
adopted schizos who had paternal half sibs who were also adopted – 8/63 of
those half sibs also schizo
Dopamine Hypothesis
Schizophrenia
results from
or
is associated with over-
activity
of DA synapses.
Drug-Induced
Psychosis
z
amphetamine
or cocaine use increases DA activity
and can trigger paranoid schizophrenia
z
excess
l-dopa can cause symptoms of schizophrenia in Parkinson’s patients
z
amphetamine
or l-dopa given to schizophrenics worsens their symptoms
Antipsychotics
Neuroleptics or
Antipsychotics
z
~
10 phenothiazines like chlorpromazine (Thorazine)-”typical antipsychotic”
z
butyrophenones
like haloperidol (Haldol)
z
all
of these block DA receptors
z
seem
to act on mesolimbic DA pathway
Too Much DA
Blockade?
z
typical
antipsychotics block DA receptors all over brain
z
anti-DA
action in basal ganglia causes appearance of Parkinson’s disease symptoms and
tardive dyskinesia
z
“Atypical
antipsychotics” like Clozaril or Risperdal block mostly limbic receptors(D4),
not basal ganglia(D2): fewer motor problems.
Problems With DA
Theory
z
Most
studies have found normal levels of DA in schizos. There is, however, some
evidence of abnormal #’s of different
DA receptors.
z
Antipsychotics
block DA immediately but therapeutic effect builds over weeks
z
Differences
noted in other transmitters
Glutamate
Hypothesis
z
Underlying
problem in schizophrenia is underactivity of glutamate, especially in frontal
lobe.
z
This
does not necessarily conflict with the DA hypothesis because these
neurotransmitter systems interact.
z
PCP
(phencyclidine) acts by inhibiting glutamate receptors & it produces both
positive and negative symptoms of schizophrenia.
PET Scans
Brain Changes
z
enlarged
ventricles
z
Smaller
thalamus, frontal & temporal cortex, amygdala, hippocampus, especially on
left side
z
6%
decrease in brain weight on average
z
loss
of cells/disorganized cells, mostly in frontal & temporal lobes &
hippocampus
z
Changes/disorganization
present since birth and are not progressive, but effects may not become
apparent until we reach the age where those brain areas mature & normally
become fully functional
Functional
Differences
z
less
brain activity in these regions
z
less
frontal activity during tasks
z
signs
of less sharing across corpus callosum, less lateralization
z
problems
with memory tasks
z
some
of these changes also present in nonschizophrenic family members
Neurodevelopmental
Theory
z
Brain
abnormalities associated with schizo begin prenatally or neonatally
z
May
reflect not only genetically based differences but adverse prenatal/neonatal
conditions as well
z
Birth
records of schizos show more “nonoptimal” signs during preg/labor (nutritional
deficiencies, illness during pregnancy, Rh incompatibility, prematurity,
delivery complications, low birth weight, etc.)
Season-of-Birth
Effect
z
More
schizophrenics are born in winter/early spring, especially those with no family
history of schizophrenia
z
Higher
rate of schizophrenia in those born in winters of years with fall viral
epidemics
z
If
a viral epidemic occurs in other seasons, there is more schizophrenia among
those born 3 months later