Prepared by Jeffrey W. Grimm Western Washington University

Prepared by Jeffrey W. Grimm Western Washington University
PowerPoint Presentation for Biopsychology, 8th Edition by John P.J. Pinel Prepared by Jeffrey W. Grimm Western Washington University 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 © 2011 Pearson Education, Inc. All rights reserved.

Psychiatric Disorders
Disorders of psychological function that require treatment Diagnosis is guided by the DSM of the American Psychiatric Association Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 two needed for one month for diagnosis Copyright © 2011 Pearson Education, Inc. All rights reserved.

Causal Factors in Schizophrenia
Evidence for a genetic contribution 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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Dopamine Theory of Schizophrenia
1960 – link between dopamine and Parkinson’s disease established Antipsychotic drug side effects suggests role for dopamine – drugs work by decreasing dopamine levels; schizophrenia associated with dopamine overactivity Reserpine depletes brain of dopamine and other monoamines by making vesicles leaky Amphetamine and cocaine are dopamine agonists and produce psychosis Copyright © 2011 Pearson Education, Inc. All rights reserved.

Dopamine Theory of Schizophrenia Continued
Chlorpromazine antagonizes dopamine activity by binding and blocking dopamine receptors In general, the higher affinity a drug has for dopamine 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 butyro-phenones bind to D2 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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. Copyright © 2011 Pearson Education, Inc. All rights reserved.

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.) Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 associated with brain damage Little damage to dopamine circuitry Damage not explained by dopamine theory Neuroleptics are only effective for some Copyright © 2011 Pearson Education, Inc. All rights reserved.

Limitations of the Dopamine Theory Continued
Positive symptoms – presence of abnormal incoherence, hallucinations, delusions Negative symptoms– absence of normal flat affect, cognitive deficits, little speech Conventional neuroleptics (D2 blockers) mainly effective for positive symptoms Negative symptoms might be caused by brain damage May be best to think of schizophrenia as multiple disorders with multiple causes Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Causal Factors in Affective Disorders
Affective disorders are very common ~5% suffer from unipolar affective disorder at some point, ~1% from bipolar Genetics Concordance rate higher for bipolar than unipolar Copyright © 2011 Pearson Education, Inc. All rights reserved.

Causal Factors in Affective Disorders Continued
Stressful experiences Evidence linking stress and affective disorders is sparse Extreme stress is more likely to cause post-traumatic stress disorder (PTSD) than depression Seasonal Affective Disorder (SAD) Wintertime depression and lethargy Probably due to reduction of sunlight More common in northern than southern latitudes Light therapy helps Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Selective Monoamine Reuptake Inhibitors
Selective serotonin-reuptake inhibitors (SSRIs), for example Include Prozac, Paxil, Zoloft, and others 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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Effectiveness of Drugs in the Treatment of Affective Disorders
2002 study: results are about the same for MAOIs, tricyclics, and SSRIs: about 50% improve, compared to 25% of controls 2008 study: meta-analysis indicated that placebo was about 82% as effective as anti-depressants in severely depressed individuals Drugs even less effective for mild to moderately depressed individuals Copyright © 2011 Pearson Education, Inc. All rights reserved.

Brain Pathology and Bipolar Affective Disorder
Inconclusive evidence for reduction of size of brain or 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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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. Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 respond to monoamine agonists Copyright © 2011 Pearson Education, Inc. All rights reserved.

Diathesis-Stress Model of Depression
Diathesis = 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 in many depressed patients Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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. Copyright © 2011 Pearson Education, Inc. All rights reserved.

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. The most prevalent psychiatric disorders Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

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) Re-duce anxiety without sedation, side effects Antidepressants – effective due to comorbidity of anxiety and depression Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Validated by effectiveness of benzodiaze-pines – but not all anxiety treated with such drugs Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 obvious structural pathology yet identified Some evidence for over-activity in the amygdalae of patients with a phobia viewing the feared object Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 No animal models, no genes identified, imaging difficult due to tics Patients tend to have smaller caudate nuclei Copyright © 2011 Pearson Education, Inc. All rights reserved.

Tourette Syndrome: Treatment
Usually treated with neuroleptics – although effectiveness is not well-established Effectiveness of D2 blockers suggests abnormality in basal ganglia-thalamus-cortex feedback circuit Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Clinical Trials: Development of New Psychotherapeutic Drugs Continued
Controversial aspects of clinical trials Requirement for double-blind design and placebo controls: potentially effective drug withheld from desperate patients randomly assigned to control group The need for active placebos: have side effects but no therapeutic value Length of time required Copyright © 2011 Pearson Education, Inc. All rights reserved.

Clinical Trials: Development of New Psychotherapeutic Drugs Continued 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) Copyright © 2011 Pearson Education, Inc. All rights reserved.

Other Treatments for Affective Disorders
Sleep deprivation More than 50% of depressed patients improve after one night of sleep deprivation Depression returns with normal sleep pattern Not explained by any current theory Exercise Helps reduce depression Increases adult hippocampal neurogenesis Findings suggests that depression may be caused by reduced adult hippocampal neurogenesis Copyright © 2011 Pearson Education, Inc. All rights reserved.

Prepared by Jeffrey W. Grimm Western Washington University

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