1. 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 Copyright © 2007 by Allyn and Bacon Chapter 15 Behavioral Neuroscience of Psychiatric Disorders The Brain Unhinged

2. 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

3. Copyright © 2007 by Allyn and Bacon Psychiatric Disorders More influenced by experiential factors Tend to be the product of more subtle forms of brain pathology  Underlying dysfunction may yet to be identified, but are suggested by the effectiveness of treatments Tend to be less well understood

4. Copyright © 2007 by Allyn and Bacon 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?

5. Copyright © 2007 by Allyn and Bacon 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

6. Copyright © 2007 by Allyn and Bacon 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

7. Copyright © 2007 by Allyn and Bacon 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?

8. Copyright © 2007 by Allyn and Bacon 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

9. Copyright © 2007 by Allyn and Bacon 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 D 1 and D 2 receptors, it and the other butyrophenones bind to D 2 Degree that neuroleptics bind to D 2 receptors is correlated with their effectiveness

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12. Problems with the D 2 Theory Clozapine, an atypical and effective neuroleptic, acts at D 1, D 4, and serotonin receptors. But – some binding to D 2 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

13. Copyright © 2007 by Allyn and Bacon Problems with the D 2 Theory Positive symptoms - presence of abnormal  incoherence, hallucinations, delusions Negative – absence of normal  flat affect, cognitive deficits, little speech Conventional neuroleptics (D 2 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

14. Copyright © 2007 by Allyn and Bacon 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 event  Endogenous – no apparent cause

15. Copyright © 2007 by Allyn and Bacon 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

16. Copyright © 2007 by Allyn and Bacon 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

17. Copyright © 2007 by Allyn and Bacon 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

18. Copyright © 2007 by Allyn and Bacon 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

19. Copyright © 2007 by Allyn and Bacon Monoamine Theory of Depression Underactivity of the monoamines serotonin and norepinephrine Consistent with drug effects  Up-regulation of receptors at autopsy of depressed individuals consistent with this Problem with theory – not all respond to monoamine agonists

20. Copyright © 2007 by Allyn and Bacon How Prozac Works

21. Copyright © 2007 by Allyn and Bacon Diathesis-Stress Model Inherited 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

22. Copyright © 2007 by Allyn and Bacon 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?

23. Copyright © 2007 by Allyn and Bacon Brain Damage and Unipolar Depression Amygdala Prefrontal cortex  Both involved in perception and experience of emotion Terminal structures of the mesotelencephalic DA system  Consistent with anhedonia (lack of pleasure) experienced by the depressed

24. Copyright © 2007 by Allyn and Bacon 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. Most prevalent psychiatric disorders

25. Copyright © 2007 by Allyn and Bacon 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

26. Copyright © 2007 by Allyn and Bacon Treatment of Anxiety Disorders Benzodiazepines (Librium, Valium)  Also used as hypnotics, anticonvulsants, muscle relaxants  GABA A agonists – bind to receptor and facilitate effects of GABA  Highly addictive Serotonin agonists (Buspirone, SSRIs)  Reduce anxiety without sedation and other side effects

27. Copyright © 2007 by Allyn and Bacon 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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29. 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 pathology yet identified

30. Copyright © 2007 by Allyn and Bacon 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

31. Copyright © 2007 by Allyn and Bacon Tourette’s Syndrome Usually treated with neuroleptics – although effectiveness is not well- established Effectiveness of D 2 blockers suggests abnormality in basal ganglia-thalamus- cortex feedback circuit