Chapter 15 Behavioral Neuroscience of Psychiatric Disorders The Brain Unhinged
Psychiatric Disorders <ul><li>AKA psychological disorders </li></ul><ul><li>Disorders of psychological function that warra...
Psychiatric Disorders <ul><li>More influenced by experiential factors </li></ul><ul><li>Tend to be the product of more sub...
Psychiatric Disorders <ul><li>What are the advantages and disadvantages of societal acceptance of psychological disorders ...
Schizophrenia <ul><li>“ splitting of psychic functions” </li></ul><ul><ul><li>Refers to the breakdown of integration of em...
Causal Factors in Schizophrenia <ul><li>Clear genetic basis </li></ul><ul><ul><li>Inherit an increased risk for the disord...
Antipsychotic Drugs <ul><li>Much of our understanding of schizophrenia is a consequence of the drugs that are able to trea...
Dopamine (DA) Theory of Schizophrenia <ul><li>1960 – link between DA and Parkinson’s Disease established </li></ul><ul><li...
Dopamine (DA) Theory of Schizophrenia <ul><li>In general, the higher affinity a drug has for DA receptors, the more effect...
 
 
Problems with the D 2  Theory <ul><li>Clozapine, an atypical and effective neuroleptic, acts at D 1 , D 4 , and serotonin ...
Problems with the D 2  Theory <ul><li>Positive symptoms  - presence of abnormal </li></ul><ul><ul><li>incoherence, halluci...
Affective Disorders <ul><li>Depression – normal reaction to loss, abnormal when it persists or has no cause </li></ul><ul>...
Causal Factors in Affective Disorders <ul><li>Affective disorders are very common </li></ul><ul><ul><li>~6% suffer from un...
Antidepressant Drugs <ul><li>Monoamine oxidase inhibitors (MAOIs) </li></ul><ul><ul><li>Prevent breakdown of monoamines </...
Selective monoamine reuptake inhibitors <ul><li>Selective serotonin-reuptake inhibitors (SSRIs) </li></ul><ul><ul><li>Proz...
Effectiveness of Drug in Treating Affective Disorders  <ul><li>Results are comparable with MAOIs, tricyclics, and SSRIs </...
Monoamine Theory of Depression <ul><li>Underactivity of the monoamines serotonin and norepinephrine  </li></ul><ul><li>Con...
How Prozac Works
Diathesis-Stress Model <ul><li>Inherited genetic susceptibility (diathesis) + stress = depression </li></ul><ul><li>Suppor...
Sleep Deprivation <ul><li>More than 50% of depressed patients improve after one night of sleep deprivation </li></ul><ul><...
Brain Damage and Unipolar Depression <ul><li>Amygdala </li></ul><ul><li>Prefrontal cortex </li></ul><ul><ul><li>Both invol...
Anxiety Disorders  <ul><li>Anxiety – fear in the absence of threat  </li></ul><ul><li>Anxiety disorder – when anxiety inte...
Anxiety Disorders <ul><li>Generalized – stress and anxiety in the absence of a causal stimulus </li></ul><ul><li>Phobic – ...
Treatment of Anxiety Disorders <ul><li>Benzodiazepines (Librium, Valium) </li></ul><ul><ul><li>Also used as hypnotics, ant...
Animal Models of Anxiety <ul><li>Assess anxiolytic potential of drugs - assume that defensive behaviors are motivated by f...
 
Neural Bases of Anxiety Disorders <ul><li>Drugs suggest a role for serotonin and GABA </li></ul><ul><li>Amygdala, due to i...
Tourette’s Syndrome  <ul><li>A disorder of tics, involuntary movements or vocalizations </li></ul><ul><li>Begins in childh...
Tourette’s Syndrome  <ul><li>Usually treated with neuroleptics – although effectiveness is not well-established </li></ul>...
Bringing a Drug to Market
New Drugs <ul><li>Why does it take so long for new drugs to be brought to market? </li></ul><ul><li>Have we become a socie...
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Pinel basics ch15

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Pinel basics ch15

  1. 1. Chapter 15 Behavioral Neuroscience of Psychiatric Disorders The Brain Unhinged
  2. 2. Psychiatric Disorders <ul><li>AKA psychological disorders </li></ul><ul><li>Disorders of psychological function that warrant treatment by a mental health professional </li></ul><ul><li>Neuropsychological disorders - a product of dysfunctional brains – but so are psychiatric disorders </li></ul><ul><li>Historically: </li></ul><ul><ul><li>Neuropsychological disorders – brain problem </li></ul></ul><ul><ul><li>Psychiatric – mind problem </li></ul></ul>
  3. 3. Psychiatric Disorders <ul><li>More influenced by experiential factors </li></ul><ul><li>Tend to be the product of more subtle forms of brain pathology </li></ul><ul><ul><li>Underlying dysfunction may yet to be identified, but are suggested by the effectiveness of treatments </li></ul></ul><ul><li>Tend to be less well understood </li></ul>
  4. 4. Psychiatric Disorders <ul><li>What are the advantages and disadvantages of societal acceptance of psychological disorders as diseases with a biological basis? </li></ul><ul><li>Are there some conditions for which this acceptance already exists? </li></ul>
  5. 5. Schizophrenia <ul><li>“ splitting of psychic functions” </li></ul><ul><ul><li>Refers to the breakdown of integration of emotion, thought, and action </li></ul></ul><ul><li>Affects 1% of the population </li></ul><ul><li>A diverse disorder – multiple types exist with varied profiles </li></ul><ul><li>Some symptoms: delusions, hallucinations, odd behavior, incoherent thought, inappropriate affect </li></ul><ul><ul><li>Only 1 needed for 8 months for diagnosis </li></ul></ul>
  6. 6. Causal Factors in Schizophrenia <ul><li>Clear genetic basis </li></ul><ul><ul><li>Inherit an increased risk for the disorder </li></ul></ul><ul><li>Multiple causes </li></ul><ul><ul><li>Several different chromosomes implicated </li></ul></ul><ul><ul><li>Associated with various early insults – infections, autoimmune reactions, toxins, traumatic injury, stress </li></ul></ul><ul><li>Appears that interference with the normal development of susceptible individuals may lead to development of the disorder </li></ul>
  7. 7. Antipsychotic Drugs <ul><li>Much of our understanding of schizophrenia is a consequence of the drugs that are able to treat it </li></ul><ul><li>Chlorpromazine – calms many agitated schizophrenics and activates many emotionally blunt </li></ul><ul><li>Reserpine – also found to be effective </li></ul><ul><li>Both drugs are not effective for 2-3 weeks and Parkinson-like motor effects are seen </li></ul><ul><ul><li>Suggesting a role for what neurotransmitter? </li></ul></ul>
  8. 8. Dopamine (DA) Theory of Schizophrenia <ul><li>1960 – link between DA and Parkinson’s Disease established </li></ul><ul><li>Side effects of antipsychotic drugs suggests role for dopamine: Drugs work by decreasing DA levels, disorder is a consequence of DA overactivity </li></ul><ul><ul><li>Reserpine depletes brain of DA and other monoamines by making vesicles leaky </li></ul></ul><ul><ul><li>Amphetamine and cocaine are DA agonists and produce psychosis </li></ul></ul><ul><ul><li>Chlorpromazine antagonizes DA activity by binding and blocking DA receptors </li></ul></ul>
  9. 9. Dopamine (DA) Theory of Schizophrenia <ul><li>In general, the higher affinity a drug has for DA receptors, the more effective it is in treating schizophrenia </li></ul><ul><li>Haloperidol – an exception </li></ul><ul><ul><li>While most antipsychotics bind to D 1 and D 2 receptors, it and the other butyrophenones bind to D 2 </li></ul></ul><ul><li>Degree that neuroleptics bind to D 2 receptors is correlated with their effectiveness </li></ul>
  10. 12. Problems with the D 2 Theory <ul><li>Clozapine, an atypical and effective neuroleptic, acts at D 1 , D 4 , and serotonin receptors. But – some binding to D 2 </li></ul><ul><li>Neuroleptics act quickly at the synapse, but don’t alleviate symptoms for weeks. </li></ul><ul><ul><li>Indicates some slow-acting change must occur. </li></ul></ul><ul><li>Schizophrenia associated with brain damage. </li></ul><ul><ul><li>Little damage to DA circuitry </li></ul></ul><ul><ul><li>Damage not explained by DA theory </li></ul></ul><ul><li>Neuroleptics are only effective for some </li></ul>
  11. 13. Problems with the D 2 Theory <ul><li>Positive symptoms - presence of abnormal </li></ul><ul><ul><li>incoherence, hallucinations, delusions </li></ul></ul><ul><li>Negative – absence of normal </li></ul><ul><ul><li>flat affect, cognitive deficits, little speech </li></ul></ul><ul><li>Conventional neuroleptics (D 2 blockers) mainly effective at treating positive </li></ul><ul><li>Negative – might be caused by brain damage </li></ul><ul><li>May be best to think of schizophrenia as multiple disorders with multiple causes </li></ul>
  12. 14. Affective Disorders <ul><li>Depression – normal reaction to loss, abnormal when it persists or has no cause </li></ul><ul><li>Mania – opposite of depression </li></ul><ul><li>Bipolar affective disorder </li></ul><ul><ul><li>Depression with periods of mania </li></ul></ul><ul><li>Unipolar – depression only </li></ul><ul><ul><li>Reactive – triggered by negative event </li></ul></ul><ul><ul><li>Endogenous – no apparent cause </li></ul></ul>
  13. 15. Causal Factors in Affective Disorders <ul><li>Affective disorders are very common </li></ul><ul><ul><li>~6% suffer from unipolar affective disorder at some point, ~1% from bipolar </li></ul></ul><ul><li>Genetics </li></ul><ul><ul><li>Concordance rate higher for bipolar than unipolar </li></ul></ul><ul><li>Stressful experiences </li></ul><ul><ul><li>More stress reported by those seeking treatment for depression than controls </li></ul></ul>
  14. 16. Antidepressant Drugs <ul><li>Monoamine oxidase inhibitors (MAOIs) </li></ul><ul><ul><li>Prevent breakdown of monoamines </li></ul></ul><ul><ul><li>Must avoid foods high in tyramine – ‘cheese effect’ </li></ul></ul><ul><li>Tricyclic antidepressants </li></ul><ul><ul><li>Block reuptake of serotonin and norepinephrine </li></ul></ul><ul><ul><li>Safer than MAOIs </li></ul></ul><ul><li>Selective monoamine reuptake inhibitors </li></ul><ul><li>Lithium – mood stabilizer </li></ul><ul><ul><li>Not a drug – treats bipolar </li></ul></ul>
  15. 17. Selective monoamine reuptake inhibitors <ul><li>Selective serotonin-reuptake inhibitors (SSRIs) </li></ul><ul><ul><li>Prozac, Paxil, Zoloft </li></ul></ul><ul><ul><li>No more effective than tricyclics, but side effects are few and they are effective at treating other things </li></ul></ul><ul><li>Selective norepinephrine-reuptake inhibitors (SNRIs) </li></ul><ul><ul><li>Also effective </li></ul></ul>
  16. 18. Effectiveness of Drug in Treating Affective Disorders <ul><li>Results are comparable with MAOIs, tricyclics, and SSRIs </li></ul><ul><ul><li>About 50% improve, compared to 25% of controls </li></ul></ul><ul><li>Drugs help those experiencing depression, but do not prevent future episodes </li></ul>
  17. 19. Monoamine Theory of Depression <ul><li>Underactivity of the monoamines serotonin and norepinephrine </li></ul><ul><li>Consistent with drug effects </li></ul><ul><ul><li>Up-regulation of receptors at autopsy of depressed individuals consistent with this </li></ul></ul><ul><li>Problem with theory – not all respond to monoamine agonists </li></ul>
  18. 20. How Prozac Works
  19. 21. Diathesis-Stress Model <ul><li>Inherited genetic susceptibility (diathesis) + stress = depression </li></ul><ul><li>Support is indirect </li></ul><ul><ul><li>Depressed people tend to release more stress hormones </li></ul></ul><ul><ul><li>Fail dexamethasone suppression test – normal negative feedback on stress hormones not functioning </li></ul></ul>
  20. 22. Sleep Deprivation <ul><li>More than 50% of depressed patients improve after one night of sleep deprivation </li></ul><ul><li>Short-lasting: depression returns when normal sleep pattern resumes </li></ul><ul><li>Not explained by any theory </li></ul><ul><li>What does this suggest? </li></ul>
  21. 23. Brain Damage and Unipolar Depression <ul><li>Amygdala </li></ul><ul><li>Prefrontal cortex </li></ul><ul><ul><li>Both involved in perception and experience of emotion </li></ul></ul><ul><li>Terminal structures of the mesotelencephalic DA system </li></ul><ul><ul><li>Consistent with anhedonia (lack of pleasure) experienced by the depressed </li></ul></ul>
  22. 24. Anxiety Disorders <ul><li>Anxiety – fear in the absence of threat </li></ul><ul><li>Anxiety disorder – when anxiety interferes with normal functioning </li></ul><ul><ul><li>Accompanied by physiological symptoms – tachycardia, hypertension, sleep disturbances, nausea, etc. </li></ul></ul><ul><li>Most prevalent psychiatric disorders </li></ul>
  23. 25. Anxiety Disorders <ul><li>Generalized – stress and anxiety in the absence of a causal stimulus </li></ul><ul><li>Phobic – similar to generalized, but triggered by a stimulus </li></ul><ul><li>Panic disorders – may occur with other disorders, but also alone </li></ul><ul><li>Obsessive-compulsive disorders (OCDs) – obsessive thoughts alleviated by compulsive actions </li></ul><ul><li>Posttraumatic stress disorder </li></ul>
  24. 26. Treatment of Anxiety Disorders <ul><li>Benzodiazepines (Librium, Valium) </li></ul><ul><ul><li>Also used as hypnotics, anticonvulsants, muscle relaxants </li></ul></ul><ul><ul><li>GABA A agonists – bind to receptor and facilitate effects of GABA </li></ul></ul><ul><ul><li>Highly addictive </li></ul></ul><ul><li>Serotonin agonists (Buspirone, SSRIs) </li></ul><ul><ul><li>Reduce anxiety without sedation and other side effects </li></ul></ul>
  25. 27. Animal Models of Anxiety <ul><li>Assess anxiolytic potential of drugs - assume that defensive behaviors are motivated by fear, and that fear and anxiety are comparable </li></ul><ul><ul><li>Elevated-plus-maze: time in open arms indicates less anxiety </li></ul></ul><ul><ul><li>Defensive-burying: More time burying, more anxiety </li></ul></ul><ul><ul><li>Risk-assessment test: Time freezing and assessing risk indicate anxiety level </li></ul></ul><ul><li>Validated by effectiveness of benzodiazepines – but not all anxiety treated with such drugs </li></ul>
  26. 29. Neural Bases of Anxiety Disorders <ul><li>Drugs suggest a role for serotonin and GABA </li></ul><ul><li>Amygdala, due to its role in fear and defensive behavior, thought to be involved </li></ul><ul><ul><li>No pathology yet identified </li></ul></ul>
  27. 30. Tourette’s Syndrome <ul><li>A disorder of tics, involuntary movements or vocalizations </li></ul><ul><li>Begins in childhood </li></ul><ul><li>Major genetic component </li></ul><ul><li>Many also have signs of ADHD and/or OCD </li></ul><ul><li>No animal models, no genes identified, imaging difficult due to tics </li></ul>
  28. 31. Tourette’s Syndrome <ul><li>Usually treated with neuroleptics – although effectiveness is not well-established </li></ul><ul><li>Effectiveness of D 2 blockers suggests abnormality in basal ganglia-thalamus-cortex feedback circuit </li></ul>
  29. 32. Bringing a Drug to Market
  30. 33. New Drugs <ul><li>Why does it take so long for new drugs to be brought to market? </li></ul><ul><li>Have we become a society that believes in better living through chemistry? </li></ul>

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