1. Prepared by Jeffrey W. Grimm Western Washington University
PowerPoint Presentation for Biopsychology, 9th Edition by John P.J. Pinel
Prepared by Jeffrey W. Grimm
Western Washington University
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Chapter 18
Biopsychology of
Psychiatric Disorders
The Brain Unhinged
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Learning Objectives
LO1: Describe the evolution of the dopamine theory of schizophrenia.
LO2: Summarize current biopsychological research and treatment of schizophrenia.
LO3: Summarize current biopsychological research and treatment of affective disorders.
LO4: Describe 5 anxiety disorders.
LO5: Which drugs are used in the treatment of anxiety disorders?
LO6: Describe Tourette syndrome, its neural correlates, and treatment.
LO7: Explain: Tourette syndrome is more a disorder of the onlooker than of the patient.
LO8: Describe the 3 phases of clinical trials.
LO9: Discuss controversial aspects of clinical trials.
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4. Psychiatric Disorders
Disorders of Psychological Function that Require Treatment
Diagnosis is guided by the DSM of the American Psychiatric Association (currently the DSM V).
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Schizophrenia
“Splitting of Psychic Functions”
Refers to the breakdown of integration of emotion, thought, and action
Affects 1 Percent of the Population
A diverse disorder: multiple types exist, with varied profiles.
Some symptoms: delusions, hallucinations, odd behavior, incoherent thought, inappropriate affect
Only two need be present for one month for diagnosis.
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6. Causal Factors in Schizophrenia
Evidence for a Genetic Contribution
Inherit an increased risk for the disorder
Multiple Causes
Several different chromosomes have been implicate.
Associated with various early insults: infections, autoimmune reactions, toxins, traumatic injury, stress
It appears that interference with the normal development of susceptible individuals may lead to development of the disorder.
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7. Discovery of the First 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 schizophrenics
Reserpine: also found to be effective, no longer used
Both drugs are not effective for 2–3 weeks, and Parkinson-like motor effects are seen.
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8. Dopamine Theory of Schizophrenia
In 1960, the link between dopamine and Parkinson’s disease was established.
Antipsychotic drug side effects suggests a role for dopamine; the drugs work by decreasing dopamine levels, and schizophrenia is associated with high levels of dopamine.
Reserpine depletes the brain of dopamine and other monoamines by making vesicles leaky.
Amphetamine and cocaine are dopamine agonists and produce psychosis.
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9. Dopamine Theory of Schizophrenia (Con’t)
In general, the higher affinity a drug has for dopamine receptors, the more effective it is in treating schizophrenia.
Haloperidol is an exception. While most antipsychotics bind to D1 and D2 receptors, it and the other butyro-phenones bind to D2
Chlorpromazine antagonizes dopamine activity by binding and blocking dopamine receptors.
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FIGURE 18.1 Chlorpromazine is a receptor blocker at dopamine synapses. Chlorpromazine was the first receptor blocker to be identified, and its discovery changed psychopharmacology.
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FIGURE 18.2 The positive correlation between the ability of various neuroleptics to bind to D2 receptors and their clinical potency. (Based on Snyder, 1978.)
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12. Limitations of the Dopamine Theory
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 is associated with brain damage.
Little damage to dopamine circuitry
Damage not explained by dopamine theory
Neuroleptics are only effective for some people.
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13. Limitations of the Dopamine Theory (Con’t)
Conventional neuroleptics (D2 blockers) are mainly effective for positive symptoms.
Negative symptoms might be caused by brain damage.
Positive symptoms: presence of abnormal
Incoherence, hallucinations, delusions
Negative symptoms: absence of normal
Flat affect, cognitive deficits, little speech
It may be best to think of schizophrenia as multiple disorders with multiple causes—dopamine at D2 receptors is just one important factor in the disease.
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14. Schizophrenia: Current Research and Treatment
Atypical neuroleptics treat some symptoms of schizophrenia without directly affecting dopamine D2 receptors.
Studies examine the effects of psychedelic drugs (e.g., LSD) as modeling positive symptoms and dissociate anesthetics (e.g., ketamine) as modeling negative symptoms.
Genetic marker research is mixed, but shows some relationship between proposed markers for schizophrenia and other psychiatric and neurological disorders.
There is a consistent link between damaged brain tissue and schizophrenia.
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FIGURE 18.4 Structural MRIs reveal cortical loss in adolescent patients with schizophrenia. Here dark blue indicates normal areas and red indicates areas of greatest tissue loss. (From Thompson et al., 2001.)
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16. Affective Disorders: Depression and Mania
Depression: normal reaction to loss; abnormal when it persists or has no cause
Mania: overconfidence, impulsivity, distractibility, and high energy
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17. Major Categories of Affective Disorders
Psychiatric disorders characterized by disturbances of mood or emotion
Also known as mood disorders
Include depression and mania
Types of Depression
Unipolar or bipolar
Reactive vs. endogenous
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18. Causal Factors in Affective Disorders
Affective disorders are very common.
Approximately 5 percent of people suffer from unipolar affective disorder at some point—approximately 1 percent suffer from bipolar.
Genetics
Concordance rate higher for bipolar than unipolar
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19. Causal Factors in Affective Disorders (Con’t)
Stressful Experiences
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)
Wintertime depression and lethargy
Probably due to reduction of sunlight
More common in northern than in southern latitudes
Light therapy helps.
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20. Discovery of Antidepressant Drugs
Monoamine Oxidase Inhibitors (MAOIs): Iproniazid
Prevent breakdown of monoamines
Must avoid foods high in tyramine—“cheese effect”
Tricyclic Antidepressants: Imipramine
Block reuptake of serotonin and norepinephrine
Safer than MAOIs
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21. Selective Monoamine Reuptake Inhibitors
Selective Serotonin-Reuptake Inhibitors (SSRIs), for Example
Include Prozac, Paxil, Zoloft, and others
SSRIs are 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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FIGURE 18.5 Blocking of serotonin reuptake by fluoxetine (Prozac).
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Mood Stabilizers
Lithium: mood stabilizer for bipolar disorder
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24. Effectiveness of Drugs in the Treatment of Affective Disorders
According to a 2002 study, results are about the same for MAOIs, tricyclics, and SSRIs; about 50 percent improve, compared to 25 percent of controls.
A 2008 meta-analysis indicated that placebo was about 82 percent as effective as antidepressants in severely depressed individuals.
Drugs are even less effective for mild to moderately depressed individuals
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25. Brain Pathology and Bipolar Affective Disorder
There is inconclusive evidence for the reduction of size of the brain or its individual components due to bipolar affective disorder (MRI data).
Reports of shrinkage of amygdala, cingulate cortex, prefrontal cortex
Most consistent findings with amygdala and anterior cingulate cortex
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FIGURE 18.6 Structural MRIs of healthy volunteers with a genetic predisposition to developing depression reveals cell loss in the anterior cingulate and the amygdala.
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27. Monoamine Theory of Depression
Underactivity of Serotonin and Norepinephrine Synapses
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 depressed people respond to monoamine agonists.
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28. Diathesis-Stress Model of Depression
Diathesis = Genetic Susceptibility
Diathesis + Stress = Depression
Support is indirect: depressed people tend to release more stress hormones.
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29. Treatment of Depression with Brain Stimulation
2008 study found that chronic electrical stimulation near the anterior cingulate gyrus helped relieve depression in treatment-resistant patients.
Those findings have recently been replicated.
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FIGURE 18.8 The site in the anterior cingulate gyrus at which chronic brain stimulation to subcortical white matter alleviated symptoms in treatment-resistant depressed patients.
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Anxiety Disorders
Anxiety: fear in the absence of threat
Anxiety disorder: anxiety interferes with normal functioning
Accompanied by physiological symptoms: tachycardia, hypertension, sleep disturbances, nausea, etc.
The Most Prevalent Psychiatric Disorders
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32. Five Classes of Anxiety Disorders
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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33. Etiology of Anxiety Disorders
There is good evidence for a genetic contribution.
However, no specific genes have been linked to anxiety disorders.
The role of life experiences is also critical.
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34. Pharmacological 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, SSRI) reduce anxiety without sedation or serious side effects.
Antidepressants are effective due to the comorbidity of anxiety and depression.
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35. Animal Models of Anxiety
Assess anxiolytic potential of drugs: assume that defensive behaviors triggered by fear, and that fear and anxiety are comparable.
Elevated-plus-maze test: time in open arms indicates less anxiety
Defensive-burying test: time burying is measure of anxiety
Risk-assessment test: time freezing and assessing risk indicate anxiety level
This is validated by the effectiveness of benzodiazapines—but not all anxiety can be treated with such drugs.
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36. Neural Bases of Anxiety Disorders
Drugs suggest a role for serotonin and GABA.
The amygdala, due to its role in fear and defensive behavior, is thought to be involved.
No obvious structural pathology has yet been identified.
There is some evidence for over-activity in the amygdalas of patients with phobias viewing the feared objects.
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Tourette Syndrome
A Disorder of Tics (Involuntary Movements) or Vocalizations
Begins in Childhood
Major Genetic Component
Many Also Have Signs of ADHD and/or OCD
There are no animal models; no relevant genes have been identified; and imaging is difficult due to tics.
Patients tend to have smaller caudate nuclei; there is evidence for the thinning of the sensorimotor cortex.
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FIGURE Structural MRIs reveal thinning of sensorimotor cortex in children with Tourette syndrome. Red and yellow indicate large areas of cortical loss. (From Sowell et al., 2008.)
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39. Tourette Syndrome: Treatment
It is usually treated with neuroleptics, although their effectiveness is not well established.
The effectiveness of D2 blockers suggests abnormality in the basal ganglia-thalamus-cortex feedback circuit.
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Clinical Trials: Development of New Psychotherapeutic Drugs
Translational Research
Research designed to translate basic scientific discoveries into effective clinical treatments
Usually moves to clinical trials of the treatment
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TABLE 18.2 Phases of Drug Development
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42. Clinical Trials: Development of New Psychotherapeutic Drugs (Con’t)
Controversial Aspects of Clinical Trials
Requirement for double-blind design and placebo controls: a potentially effective drug is withheld from desperate patients randomly assigned to the control group.
There is a need for active placebos, which have side effects but no therapeutic value.
Length of time required
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Clinical Trials: Development of New Psychotherapeutic Drugs (Con’t)
Financial Issues
Conflict of interest: drug companies test their own drugs; may forbid scientists from publishing negative findings.
Orphan drug problem: drugs for rare diseases are unprofitable.
Translational bottleneck: due to high costs of clinical trials, few scientific findings translate to new drugs.
“Clinical trials can be trustworthy, fast, or cheap; but in any one trial, only two of the three are possible.” (Zivin, 2000)
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44. Other Treatments for Affective Disorders
Sleep Deprivation
More than 50 percent of depressed patients improve after one night of sleep deprivation.
Depression returns with normal sleep pattern.
This effect is not explained by any current theory.
Exercise
Helps reduce depression
Increases adult hippocampal neurogenesis
Findings suggest that depression may be caused by reduced adult hippocampal neurogenesis.
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