Download Affective Disorders

PowerPoint Presentation for
Biopsychology, 8th Edition
by John P.J. Pinel
Prepared by Jeffrey W. Grimm
Western Washington University
Copyright © 2011 Pearson Education,
Inc. All rights reserved.
This multimedia product and its contents are protected
under copyright law. The following are prohibited by law:
• any public performance or display, including
transmission of any image over a network;
• preparation of any derivative work, including the
extraction, in whole or in part, of any images;
• any rental, lease, or lending of the program.
Chapter 18
Biopsychology of
Psychiatric Disorders
The Brain Unhinged
Copyright © 2011 Pearson Education, Inc. All rights
reserved.
Psychiatric Disorders


Disorders of psychological function that require
treatment
Diagnosis is guided by the DSM of the
American Psychiatric Association
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Schizophrenia

“Splitting of psychic functions”




Refers to the breakdown of integration of
emotion, thought, and action
Affects 1% of the population
A diverse disorder – multiple types exist
with varied profiles
Some symptoms: delusions,
hallucinations, odd behavior, incoherent
thought, inappropriate affect

Only two needed for one month for diagnosis
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Causal Factors in
Schizophrenia

Evidence for a genetic contribution


Multiple causes



Inherit an increased risk for the disorder
Several different chromosomes implicated
Associated with various early insults – infections,
autoimmune reactions, toxins, traumatic injury,
stress
Appears that interference with the normal
development of susceptible individuals may lead
to development of the disorder
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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
schizophrenics and activates many
emotionally blunt schizophrenics
Reserpine – also found to be effective, no
longer used
Both drugs are not effective for 2-3 weeks, and
Parkinson-like motor effects are seen
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Dopamine Theory
of Schizophrenia


1960 – link between dopamine and Parkinson’s
disease established
Antipsychotic drug side effects suggests role for
dopamine – drugs work by decreasing
dopamine levels; schizophrenia associated with
dopamine overactivity


Reserpine depletes brain of dopamine and other
monoamines by making vesicles leaky
Amphetamine and cocaine are dopamine
agonists and produce psychosis
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Dopamine Theory of
Schizophrenia Continued


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, it and
the other butyro-phenones bind to D2
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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.
Copyright © 2011 Pearson Education, Inc. All rights reserved.
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.)
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Limitations of the 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



Little damage to dopamine circuitry
Damage not explained by dopamine theory
Neuroleptics are only effective for some
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Limitations of the Dopamine
Theory Continued

Positive symptoms – presence of abnormal


Negative symptoms– absence of normal




incoherence, hallucinations, delusions
flat affect, cognitive deficits, little speech
Conventional neuroleptics (D2 blockers) mainly
effective for positive symptoms
Negative symptoms might be caused by brain
damage
May be best to think of schizophrenia as multiple
disorders with multiple causes
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Affective Disorders:
Depression and Mania


Depression – normal reaction to loss, abnormal
when it persists or has no cause
Mania – overconfidence, impulsivity,
distractibility, and high energy
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Major Categories of Affective
Disorders

Affective disorders




Psychiatric disorders characterized by
disturbances of mood or emotion
Also known as mood disorders
Include depression and mania
Types of depression


Unipolar or Bipolar
Reactive vs. Endogenous
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Causal Factors in Affective
Disorders

Affective disorders are very common


~5% suffer from unipolar affective disorder at
some point, ~1% from bipolar
Genetics

Concordance rate higher for bipolar than
unipolar
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Causal Factors in Affective
Disorders Continued

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


More common in northern than southern latitudes
Light therapy helps
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Discovery of Antidepressant
Drugs

Monoamine oxidase inhibitors (MAOIs) –
Iproniazid



Prevent breakdown of monoamines
Must avoid foods high in tyramine – “cheese
effect”
Tricyclic antidepressants – Imipramine


Block reuptake of serotonin and norepinephrine
Safer than MAOIs
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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
Selective norepinephrine-reuptake inhibitors
(SNRIs) are also effective
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
FIGURE 18.5 Blocking of serotonin
reuptake by fluoxetine (Prozac).
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Mood Stabilizers

Lithium – mood stabilizer for bipolar disorder
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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 antidepressants in severely depressed individuals

Drugs even less effective for mild to moderately
depressed individuals
Copyright © 2011 Pearson Education, Inc. All rights reserved.
Brain Pathology and Bipolar
Affective Disorder

Inconclusive evidence for reduction of size
of brain or individual components due to
bipolar affective disorder (MRI data)


Reports of shrinkage of amygdala, cingulate
cortex, prefrontal cortex
Most consistent findings with amygdala and
anterior cingulate cortex
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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.
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Monoamine Theory of
Depression

Underactivity of serotonin and norepinephrine
synapses



Consistent with drug effects
Depression untreated with drugs may result in
proliferation of monoamine receptors
(up-regulation), providing support for the
monoamine theory
Problem with theory – not all respond to
monoamine agonists
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Diathesis-Stress Model of
Depression



Diathesis = genetic susceptibility
Diathesis + stress = depression
Support is indirect: depressed people…


tend to release more stress hormones
fail dexamethasone suppression test – normal
negative feedback on stress hormones not
functioning in many depressed patients
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Treatment of Depression with
Brain Stimulation

2008 study found that chronic electrical
stimulation near the anterior cingulate gyrus
helped relieve depression in treatmentresistant patients
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
FIGURE 18.8 The site in the anterior cingulate
gyrus at which chronic brain stimulation to
subcortical white matter alleviated symptoms in
treatment-resistant depressed patients.
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Anxiety Disorders


Anxiety – fear in the absence of threat
Anxiety disorder – when anxiety interferes
with normal functioning


Accompanied by physiological symptoms –
tachycardia, hypertension, sleep disturbances,
nausea, etc.
The most prevalent psychiatric disorders
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Five Classes of Anxiety
Disorders





Generalized anxiety disorders – stress and
anxiety in the absence of a causal stimulus
Phobic anxiety disorders – similar to generalized,
but triggered by a particular stimulus
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
Posttraumatic stress disorder – pattern of
psychological distress following extreme stress
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Etiology of Anxiety Disorders


Good evidence for a genetic contribution
Role of life experiences is also critical
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Pharmacological Treatment of
Anxiety Disorders

Benzodiazepines (Librium, Valium)




Also used as hypnotics, anticonvulsants, muscle
relaxants
GABAA agonists – bind to receptor and facilitate
effects of GABA; highly addictive
Serotonin agonists (buspirone, SSRI) Re-duce
anxiety without sedation, side effects
Antidepressants – effective due to comorbidity of
anxiety and depression
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Animal Models of Anxiety


Assess anxiolytic potential of drugs: assume that
defensive behaviors triggered by fear, and that fear and
anxiety are comparable
 Elevated-plus-maze test: time in open arms indicates
less anxiety
 Defensive-burying test: time burying is measure of
anxiety
 Risk-assessment test: time freezing and assessing
risk indicate anxiety level
Validated by effectiveness of benzodiaze-pines – but
not all anxiety treated with such drugs
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Neural Bases 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
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Tourette Syndrome






A disorder of tics (involuntary movements) or
vocalizations
Begins in childhood
Major genetic component
Many also have signs of ADHD and/or OCD
No animal models, no genes identified,
imaging difficult due to tics
Patients tend to have smaller caudate nuclei
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Tourette Syndrome: Treatment


Usually treated with neuroleptics – although
effectiveness is not well-established
Effectiveness of D2 blockers suggests
abnormality in basal ganglia-thalamuscortex feedback circuit
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
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
Copyright © 2011 Pearson Education, Inc. All rights reserved.
FIGURE 18.12 The cost and duration of the
three phases of drug testing on human
volunteers.
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Clinical Trials: Development of
New Psychotherapeutic Drugs
Continued

Controversial aspects of clinical trials



Requirement for double-blind design and placebo
controls: potentially effective drug withheld from
desperate patients randomly assigned to control
group
The need for active placebos: have side effects
but no therapeutic value
Length of time required
Copyright © 2011 Pearson Education, Inc. All
rights reserved.
Clinical Trials: Development of
New Psychotherapeutic Drugs
Continued

Financial issues




Conflict of interest: drug companies test their own drugs; may
forbid scientists from publishing negative findings
Orphan drug problem (drugs for rare diseases are
unprofitable)
Translational bottleneck: due to high costs of clinical trials, few
scientific findings translate to new drugs
“Clinical trials can be trustworthy, fast, or cheap;
but in any one trial, only two of the three are
possible.” (Zivin, 2000)
Copyright © 2011 Pearson Education, Inc. All rights reserved.
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
Copyright © 2011 Pearson Education, Inc. All rights reserved.