Download Affective disorders

BIOPSYCHOLOGY 8e
John P.J. Pinel
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Psychiatric Disorders
• Disorders of
psychological function
that require treatment
• Diagnosis is guided by the
DSM-V of the American
Psychiatric Association
• Diagnosis is often difficult
•  Based on symptoms rather
than brain pathology
•  Similar symptoms in different
disorders
•  One disorder can present
with different symptoms
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Schizophrenia
• “Splitting of psychic
functions”
–  Refers to the
breakdown of
integration of
emotion, thought, and
action
–  Splitting of reality
from perceived reality
• Affects 1% of the population
• A diverse disorder –
multiple types exist with
varied profiles
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Schizophrenia
•  Symptoms tend to cluster into two
major categories:
•  Positive:
•  Delusions – False beliefs
•  Hallucinations – False perceptions
•  Inappropriate affect
•  Incoherent speech or thought (word
salads)
•  Odd behaviour
Negative:
Flat affect, Alogia, Avolition, Anhedonia
http://www.youtube.com/watch?
v=bWaFqw8XnpA
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Causal Factors in Schizophrenia
•  Evidence for a genetic contribution
•  Inherit an increased risk for the disorder
•  Multiple causes
•  Several different genes implicated
•  Associated with various early insults –
infections, birth complications, toxins,
traumatic injury, stress
•  Appears that interference with the normal
development of susceptible individuals may
lead to development of the disorder
•  Inherit a predisposition, on which environmental factors
then interact
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Discovery of the First Antipsychotic Drugs
•  Much of our understanding of
schizophrenia is a consequence of the
drugs that are able to treat it
•  Chlorpromazine – calms many agitated (p)
schizophrenia and activates many
emotionally blunt (p)schizophrenia
•  Reserpine (extract of snake root plant) –
also found to be effective, no longer used
•  Both drugs are not effective for 2-3 weeks,
and Parkinson-like motor effects are seen
•  Tardive dyskinesia
•  http://www.youtube.com/watch?v=t_NKRS8lLWA
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Dopamine Theory of Schizophrenia
•  1960 – link between dopamine and
Parkinson’s disease established
•  (P)Parkinson’s striatum depleted of
dopamine/(P)Schizophrenia high
levels of dopamine
•  Antipsychotic drug motor side effects
and antipsychotics work by
decreasing dopamine levels;
•  Reserpine depletes brain of
dopamine and other
monoamines by making vesicles
leaky
•  Amphetamine and cocaine are
dopamine agonists and produce
psychosis
•  Chlorpromazine antagonizes
dopamine activity by binding
and blocking dopamine
receptors
In general, the higher affinity a
drug has for dopamine
receptors, the more effective it
is in treating schizophrenia
Haloperidol – an exception.
While most antipsychotics bind
to D1 and D2 receptors, this one
selectively binds to D2
As do other drugs in the
same class as Haloperidol
D2 receptor affinity/activity
modified theory of
schizophrenia
But it doesn’t explain
everything…
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Dopamine Theory of Schizophrenia
FIGURE 18.1:
Chlorpromazine is a
receptor blocker at
dopamine synapses.
Chlorpromazine was
the first receptor
blocker to be identified,
and its discovery
changed
psychopharmacology.
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Dopamine Theory of Schizophrenia
FIGURE 18.2:
The positive
correlation between the
ability of various
neuroleptics to bind to
D2 receptors and their
clinical potency.
(Based on Snyder,
1978.)
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Limitations of the D2 Dopamine Theory
•  Clozapine, an atypical and effective
neuroleptic, acts at D1, D4, and serotonin
receptors, but has only some binding to D2
receptors
•  Neuroleptics act quickly at the synapse,
but don’t alleviate symptoms for weeks
•  Schizophrenia associated with brain
damage
•  Enlarged ventricles/fissures
•  Little damage to dopamine circuitry
•  Damage not explained by dopamine
theory as its evident early on;
continues and damage occurs at
different rates in different areas
•  Neuroleptics are only effective for some
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Major Categories of Affective Disorders
Affective disorders:
•  Psychiatric disorders
characterized by
disturbances of mood
or emotion
•  Also known as mood
disorders
•  Includes depression
and mania
•  Depression: normal when
a reaction to loss;
abnormal when it persists
or has no cause
Types of depression
• Unipolar or Bipolar
• Reactive vs. Endogenous
• Mania: overconfidence,
impulsivity, distractibility,
and high energy
• http://www.youtube.com/
watch?v=zA-fqvC02oM
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Causal Factors in Affective Disorders
• Affective disorders are very
common
–  ~10% suffer from clinical
depresssion at some point,
–  Twice as likely to be women as
men
–  Bipolar disorder shows no sex
difference
–  1-5% incidence
• Genetics
–  Although there are exceptions,
there is a tendency for affected
twins to suffer from the same
affective disorder
–  Concordance rate higher for
bipolar than unipolar
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Causal Factors in Affective Disorders
•  Stressful experiences?
–  Evidence linking stress
and affective disorders is
sparse
–  Extreme stress is more
likely to cause posttraumatic stress disorder
(PTSD) than depression
•  Seasonal Affective Disorder
(SAD)
–  Wintertime depression
and lethargy
–  Probably due to
reduction of sunlight
–  Light therapy is often
effective
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Discovery of Antidepressant Drugs
•  Monoamine oxidase inhibitors (MAOIs)
– Iproniazid
•  Prevent breakdown of monoamines
•  Must avoid foods high in tyramine –
“cheese effect” – MAO metabolizes
tyramine, but when MAO is inhibited it
causes a dangerous increase in BP
•  Tricyclic antidepressants – Imipramine
•  Block reuptake of serotonin and
norepinephrine
•  Safer than MAOIs as does not interact
with MAO
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Selective Monoamine Reuptake Inhibitors
• Selective serotonin-reuptake
inhibitors (SSRIs), for
example
•  Include Prozac, Paxil, Zoloft,
and others
•  No more effective than
tricyclics, but side effects are
few and they are effective at
treating other disorders
•  Widely prescribed
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SSRIs
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Effectiveness of Drugs in the Treatment of Affective
Disorders
•  2002 study: results are about the
same for MAOIs, tricyclics, and
SSRIs: about 50% improve,
compared to 25% of controls
•  2008 study: meta-analysis indicated
that placebo was about 82% as
effective as anti-depressants in
severely depressed individuals
•  Drugs even less effective for
mild to moderately depressed
individuals
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Other Treatments for Affective Disorders
Sleep deprivation
•  More than 50% of depressed patients improve
after one night of sleep deprivation
•  Depression returns with normal sleep pattern
•  Not explained by any current theory
Exercise
•  Helps reduce depression
•  Increases adult hippocampal neurogenesis
•  Findings suggests that depression may be
caused by reduced adult hippocampal
neurogenesis
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Brain Pathology and Bipolar Affective Disorder
• Inconclusive evidence for overall
neural atrophy or atrophy of
individual structures due to
bipolar affective disorder (MRI
data)
•  Some consistent reports of
atrophy of amygdala and
cingulate cortex
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Brain Pathology and Bipolar Affective Disorder
Figure 18.6:
Structural MRIs of
healthy volunteers with a
genetic predisposition to
developing depression
reveals cell loss in the
anterior cingulate and
the amygdala.
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Monoamine Theory of Depression
•  Underactivity of serotonin and
norepinephrine synapses
–  Consistent with drug effects –
MAOIs, SSRIs, SNRIs and tricyclics
are all agonists for S and NE.
–  Depression untreated with drugs
may result in proliferation of
monoamine receptors
(up-regulation), providing support
for the monoamine theory
•  Problem with theory – not all
(P)depression respond to
monoamine agonists
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Diathesis-Stress Model of Depression
• Diathesis = genetic susceptibility
• Diathesis + stress = depression
•  Early exposure to stress sensitizes a person
to overreact to mild stressors the rest of
their life
• Support is indirect: depressed
people…
–  tend to release more stress
hormones
–  Evidence of early stressors is
based on patient recollections
and these cannot be confirmed
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Treatment of Depression with Brain Stimulation
2008 study found
that chronic
electrical
stimulation near the
anterior cingulate
gyrus helped relieve
depression in
treatment-resistant
patients
60% showed
substantial
improvements and
35% became
symptom free.
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Anxiety Disorders
•  Anxiety – Chronic fear in the
absence of threat
•  Anxiety disorder – when anxiety
interferes with normal
functioning
•  Accompanied by
physiological symptoms of
anxiety – tachycardia,
hypertension, sleep
disturbances, nausea, etc.
•  The most prevalent psychiatric
disorders
•  Highly treatable
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Five Classes of Anxiety Disorders
•  Generalized anxiety disorders – Free floating stress
and anxiety in the absence of a causal stimulus
•  Phobic anxiety disorders – Similar to generalized,
but triggered by a particular stimulus (thunder,
spiders, heights, flying)
•  Panic disorders – Attacks of extreme fear and
stress; may occur with other disorders or alone
•  Obsessive-compulsive disorders (OCDs) –
Obsessive thoughts alleviated by compulsive
actions (counting, checking, cleaning, ordering)
•  Posttraumatic stress disorder – Pattern of
psychological distress following exposure to
extreme stress (victim of violent crime, war etc.)
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Etiology of Anxiety Disorders
•  Good evidence for a genetic
contribution (30 – 40%)
•  Role of life experiences is also
critical (obviously, as most are
triggered by some object or
situation).
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Pharmacological Treatment of Anxiety Disorders
•  Benzodiazepines (Librium, Valium)
•  Also used as hypnotics (sleep
inducing), anticonvulsants, muscle
relaxants
•  GABAA agonists – bind to receptor
and facilitate effects GABAA Agonist
•  Serotonin agonists (buspirone, SSRI) Reduce anxiety without sedation, side effects
•  Antidepressants – effective due to
comorbidity of anxiety and depression
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Neural Basis of Anxiety Disorders
• Drugs suggest a role for serotonin and GABA
•  Amygdala, due to its role in fear and
defensive behavior, thought to be
involved
–  No obvious structural pathology yet
identified
• Some evidence for over-activity in the
amygdalae of patients with a phobia viewing
the feared object (one study)
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Clinical Trials: Development of New
Psychotherapeutic Drugs
Translational research
•  Research designed to translate
basic scientific discoveries into
effective clinical treatments
•  Usually moves to clinical trials
of the treatment
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Clinical Trials: Development of New Psychotherapeutic
Drugs
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