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Chapter 15Behavioral Neuroscience of Psychiatric DisordersThe Brain Unhinged
Copyright © 2007 by Allyn and Bacon
Psychiatric Disorders
AKA psychological disorders Disorders of psychological function that warrant
treatment by a mental health professional Neuropsychological disorders - a product of
dysfunctional brains – but so are psychiatric disorders
Historically: Neuropsychological disorders – brain problem Psychiatric – mind problem
Copyright © 2007 by Allyn and Bacon
Psychiatric Disorders
More influenced by experiential factors Tend to be the product of more subtle
forms of brain pathologyUnderlying dysfunction may yet to be
identified, but are suggested by the effectiveness of treatments
Tend to be less well understood
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Psychiatric Disorders
What are the advantages and disadvantages of societal acceptance of psychological disorders as diseases with a biological basis?
Are there some conditions for which this acceptance already exists?
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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 1 needed for 8 months for diagnosis
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Causal Factors in Schizophrenia
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 Appears that interference with the normal
development of susceptible individuals may lead to development of the disorder
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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
Reserpine – also found to be effective Both drugs are not effective for 2-3 weeks and
Parkinson-like motor effects are seen Suggesting a role for what neurotransmitter?
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Dopamine (DA) Theory of Schizophrenia 1960 – link between DA and Parkinson’s Disease
established Side effects of antipsychotic drugs suggests role for
dopamine: Drugs work by decreasing DA levels, disorder is a consequence of DA overactivity Reserpine depletes brain of DA and other monoamines by
making vesicles leaky Amphetamine and cocaine are DA agonists and produce
psychosis Chlorpromazine antagonizes DA activity by binding and blocking
DA receptors
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Dopamine (DA) Theory of Schizophrenia In general, the higher affinity a drug has for DA
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 butyrophenones bind to D2
Degree that neuroleptics bind to D2 receptors is correlated with their effectiveness
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Copyright © 2007 by Allyn and Bacon
Problems with the D2 Theory
Clozapine, an atypical and effective neuroleptic, acts at D1, D4, and serotonin receptors. But – some binding to D2
Neuroleptics act quickly at the synapse, but don’t alleviate symptoms for weeks. Indicates some slow-acting change must occur.
Schizophrenia associated with brain damage. Little damage to DA circuitry Damage not explained by DA theory
Neuroleptics are only effective for some
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Problems with the D2 Theory
Positive symptoms - presence of abnormal incoherence, hallucinations, delusions
Negative – absence of normal flat affect, cognitive deficits, little speech
Conventional neuroleptics (D2 blockers) mainly effective at treating positive
Negative – might be caused by brain damage May be best to think of schizophrenia as multiple
disorders with multiple causes
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Affective Disorders
Depression – normal reaction to loss, abnormal when it persists or has no cause
Mania – opposite of depression Bipolar affective disorder
Depression with periods of mania Unipolar – depression only
Reactive – triggered by negative eventEndogenous – no apparent cause
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Causal Factors in Affective Disorders Affective disorders are very common
~6% suffer from unipolar affective disorder at some point, ~1% from bipolar
Genetics Concordance rate higher for bipolar than unipolar
Stressful experiences More stress reported by those seeking treatment for
depression than controls
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Antidepressant Drugs
Monoamine oxidase inhibitors (MAOIs) Prevent breakdown of monoamines Must avoid foods high in tyramine – ‘cheese effect’
Tricyclic antidepressants Block reuptake of serotonin and norepinephrine Safer than MAOIs
Selective monoamine reuptake inhibitors Lithium – mood stabilizer
Not a drug – treats bipolar
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Selective monoamine reuptake inhibitors Selective serotonin-reuptake inhibitors (SSRIs)
Prozac, Paxil, Zoloft No more effective than tricyclics, but side effects are
few and they are effective at treating other things
Selective norepinephrine-reuptake inhibitors (SNRIs) Also effective
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Effectiveness of Drug in Treating Affective Disorders Results are comparable with MAOIs,
tricyclics, and SSRIs About 50% improve, compared to 25% of
controls
Drugs help those experiencing depression, but do not prevent future episodes
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Monoamine Theory of Depression
Underactivity of the monoamines serotonin and norepinephrine
Consistent with drug effectsUp-regulation of receptors at autopsy of
depressed individuals consistent with this Problem with theory – not all respond to
monoamine agonists
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How Prozac Works
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Diathesis-Stress Model
Inherited genetic susceptibility (diathesis) + stress = depression
Support is indirectDepressed people tend to release more
stress hormonesFail dexamethasone suppression test –
normal negative feedback on stress hormones not functioning
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Sleep Deprivation
More than 50% of depressed patients improve after one night of sleep deprivation
Short-lasting: depression returns when normal sleep pattern resumes
Not explained by any theory What does this suggest?
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Brain Damage and Unipolar Depression Amygdala Prefrontal cortex
Both involved in perception and experience of emotion
Terminal structures of the mesotelencephalic DA systemConsistent with anhedonia (lack of pleasure)
experienced by the depressed
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Anxiety Disorders
Anxiety – fear in the absence of threat Anxiety disorder – when anxiety interferes
with normal functioningAccompanied by physiological symptoms –
tachycardia, hypertension, sleep disturbances, nausea, etc.
Most prevalent psychiatric disorders
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Anxiety Disorders
Generalized – stress and anxiety in the absence of a causal stimulus
Phobic – similar to generalized, but triggered by a stimulus
Panic disorders – may occur with other disorders, but also alone
Obsessive-compulsive disorders (OCDs) – obsessive thoughts alleviated by compulsive actions
Posttraumatic stress disorder
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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, SSRIs) Reduce anxiety without sedation and other side
effects
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Animal Models of Anxiety
Assess anxiolytic potential of drugs - assume that defensive behaviors are motivated by fear, and that fear and anxiety are comparable Elevated-plus-maze: time in open arms indicates less
anxiety Defensive-burying: More time burying, more anxiety Risk-assessment test: Time freezing and assessing
risk indicate anxiety level Validated by effectiveness of benzodiazepines –
but not all anxiety treated with such drugs
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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 involvedNo pathology yet identified
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Tourette’s 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
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Tourette’s Syndrome
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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Bringing a Drug to Market
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New Drugs
Why does it take so long for new drugs to be brought to market?
Have we become a society that believes in better living through chemistry?