Pinel basics ch15

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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



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



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?


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


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


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?


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


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


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


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


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


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


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


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


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


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


How Prozac Works


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


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?


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


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


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


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


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


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


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


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


Bringing a Drug to Market


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?

Pinel basics ch15

Health & Medicine

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