Transcript up-regulation - Bakersfield College

Chapter 18
Biopsychology of
Psychiatric Disorders
The Brain Unhinged
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Copyright © 2009 Allyn & Bacon
Psychiatric Disorders
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Also called “psychological disorders”
Disorders of psychological function that require
treatment by a mental health professional
Neuropsychological disorders are a product of
dysfunctional brains, but so are psychiatric disorders
Historical views:
 Neuropsychological disorders are brain problems
 Psychiatric disorders are mind problems
Copyright © 2009 Allyn & Bacon
Schizophrenia
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“Splitting of psychic functions”
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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
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Only two needed for one month for
diagnosis Copyright © 2009 Allyn & Bacon
Causal Factors in
Schizophrenia
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Clear genetic basis
 Inherit an increased risk for the disorder
Multiple causes
 Several different chromosomes implicated
 Associated with various early insults – infections,
autoimmune reactions, toxins, traumatic injury,
stress
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Antipsychotic Drugs
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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
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Dopamine Theory
of Schizophrenia
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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
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Dopamine Theory of
Schizophrenia (continued)
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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
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Haloperidol – an exception. While most
antipsychotics bind to D1 and D2 receptors, it and
the other butyro-phenones bind to D2
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Dopamine Theory of Schizophrenia
(continued)
Positive
correlation
between
neuroleptic
D2 binding
and clinical
potency
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Neurons derived from schizophrenic
Kristen Brennand, Salk Institute for
Biological Studies.
http://www.livescience.com/13693-schizophrenia-brain-cells-created.html
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Problems with the D2 Theory
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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
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Affective Disorders
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Depression – normal reaction to loss, abnormal when
it persists or has no cause
Mania – overconfidence, impulsivity, distract-ibility,
and high energy
Bipolar affective disorder – depression with periods of
mania
Unipolar affective disorder – depression only
 Reactive – triggered by negative event
 Endogenous – no apparent cause
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Causal Factors in Affective
Disorders (continued)
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Stressful experiences
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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)
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Wintertime depression and lethargy
Probably due to reduction of sunlight
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More common in northern than southern latitudes
Light therapy helps
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Antidepressant Drugs
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Monoamine oxidase inhibitors (MAOIs) –
Iproniazid
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Prevent breakdown of monoamines
Must avoid foods high in tyramine – “cheese
effect”
Tricyclic antidepressants – Imipramine
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Block reuptake of serotonin and norepinephrine
Safer than MAOIs
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Antidepressant Drugs (continued)
Blocking of serotonin reuptake by fluoxetine (Prozac)
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Selective Monoamine
Reuptake Inhibitors
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Selective serotonin-reuptake inhibitors
(SSRIs), for example
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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
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Brain Pathology and Bipolar
Affective Disorder
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Inconclusive evidence for reduction of size of
brain or individual components due to bipolar
affective disorder (MRI data)
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Reports of shrinkage of amygdala, striatum,
hippocampus, and prefrontal cortex, but
Meta-study found no statistically significant
evidence for brain shrinkage in bipolar patients
Copyright © 2009 Allyn & Bacon
Monoamine Theory of
Depression
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Underactivity of serotonin and norepinephrine
synapses
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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
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Anxiety Disorders
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Anxiety – fear in the absence of threat
Anxiety disorder – when anxiety interferes
with normal functioning
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Accompanied by physiological symptoms –
tachycardia, hypertension, sleep disturbances,
nausea, etc.
Most prevalent psychiatric disorders
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Five Classes of Anxiety
Disorders
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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
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Pharmacological Treatment of
Anxiety Disorders
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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) Reduce anxiety without sedation, side effects
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Neural Bases of Anxiety
Disorders
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Drugs suggest a role for serotonin and GABA
Amygdala, due to its role in fear and defensive behavior,
thought to be involved
 No pathology yet identified
Difficult to study neural basis of anxiety
 Diversity and subtlety of symptoms
 Abnormal breathing in anxious patients complicates
functional brain imaging
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Tourette Syndrome
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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
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Tourette Syndrome:
Treatment
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Usually treated with neuroleptics – although
effectiveness is not well-established
Effectiveness of D2 blockers suggests
abnormality in basal ganglia-thalamus-cortex
feedback circuit
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Perhaps a neurodevelopmental disorder from excessive
dopaminergic innervation of the striatum and associated
limbic cortex
DBS
Deep brain stimulation looks promising
DBS case
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