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BIOPSYCHOLOGY 8e John P.J. Pinel Copyright © Pearson Education 2011 Psychiatric Disorders • Disorders of psychological function that require treatment • Diagnosis is guided by the DSM-V of the American Psychiatric Association • Diagnosis is often difficult • Based on symptoms rather than brain pathology • Similar symptoms in different disorders • One disorder can present with different symptoms Copyright © Pearson Education 2011 Schizophrenia • “Splitting of psychic functions” – Refers to the breakdown of integration of emotion, thought, and action – Splitting of reality from perceived reality • Affects 1% of the population • A diverse disorder – multiple types exist with varied profiles Copyright © Pearson Education 2011 Schizophrenia • Symptoms tend to cluster into two major categories: • Positive: • Delusions – False beliefs • Hallucinations – False perceptions • Inappropriate affect • Incoherent speech or thought (word salads) • Odd behaviour Negative: Flat affect, Alogia, Avolition, Anhedonia http://www.youtube.com/watch? v=bWaFqw8XnpA Copyright © Pearson Education 2011 Causal Factors in Schizophrenia • Evidence for a genetic contribution • Inherit an increased risk for the disorder • Multiple causes • Several different genes implicated • Associated with various early insults – infections, birth complications, toxins, traumatic injury, stress • Appears that interference with the normal development of susceptible individuals may lead to development of the disorder • Inherit a predisposition, on which environmental factors then interact Copyright © Pearson Education 2011 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 (p) schizophrenia and activates many emotionally blunt (p)schizophrenia • Reserpine (extract of snake root plant) – also found to be effective, no longer used • Both drugs are not effective for 2-3 weeks, and Parkinson-like motor effects are seen • Tardive dyskinesia • http://www.youtube.com/watch?v=t_NKRS8lLWA Copyright © Pearson Education 2011 Dopamine Theory of Schizophrenia • 1960 – link between dopamine and Parkinson’s disease established • (P)Parkinson’s striatum depleted of dopamine/(P)Schizophrenia high levels of dopamine • Antipsychotic drug motor side effects and antipsychotics work by decreasing dopamine levels; • Reserpine depletes brain of dopamine and other monoamines by making vesicles leaky • Amphetamine and cocaine are dopamine agonists and produce psychosis • 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, this one selectively binds to D2 As do other drugs in the same class as Haloperidol D2 receptor affinity/activity modified theory of schizophrenia But it doesn’t explain everything… Copyright © Pearson Education 2011 Dopamine Theory of Schizophrenia 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 © Pearson Education 2011 Dopamine Theory of Schizophrenia 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 © Pearson Education 2011 Limitations of the D2 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 • Enlarged ventricles/fissures • Little damage to dopamine circuitry • Damage not explained by dopamine theory as its evident early on; continues and damage occurs at different rates in different areas • Neuroleptics are only effective for some Copyright © Pearson Education 2011 Major Categories of Affective Disorders Affective disorders: • Psychiatric disorders characterized by disturbances of mood or emotion • Also known as mood disorders • Includes depression and mania • Depression: normal when a reaction to loss; abnormal when it persists or has no cause Types of depression • Unipolar or Bipolar • Reactive vs. Endogenous • Mania: overconfidence, impulsivity, distractibility, and high energy • http://www.youtube.com/ watch?v=zA-fqvC02oM Copyright © Pearson Education 2011 Causal Factors in Affective Disorders • Affective disorders are very common – ~10% suffer from clinical depresssion at some point, – Twice as likely to be women as men – Bipolar disorder shows no sex difference – 1-5% incidence • Genetics – Although there are exceptions, there is a tendency for affected twins to suffer from the same affective disorder – Concordance rate higher for bipolar than unipolar Copyright © Pearson Education 2011 Causal Factors in Affective Disorders • 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 – Light therapy is often effective Copyright © Pearson Education 2011 Discovery of Antidepressant Drugs • Monoamine oxidase inhibitors (MAOIs) – Iproniazid • Prevent breakdown of monoamines • Must avoid foods high in tyramine – “cheese effect” – MAO metabolizes tyramine, but when MAO is inhibited it causes a dangerous increase in BP • Tricyclic antidepressants – Imipramine • Block reuptake of serotonin and norepinephrine • Safer than MAOIs as does not interact with MAO Copyright © Pearson Education 2011 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 • Widely prescribed Copyright © Pearson Education 2011 SSRIs Copyright © Pearson Education 2011 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 © Pearson Education 2011 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 © Pearson Education 2011 Brain Pathology and Bipolar Affective Disorder • Inconclusive evidence for overall neural atrophy or atrophy of individual structures due to bipolar affective disorder (MRI data) • Some consistent reports of atrophy of amygdala and cingulate cortex Copyright © Pearson Education 2011 Brain Pathology and Bipolar Affective Disorder 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 © Pearson Education 2011 Monoamine Theory of Depression • Underactivity of serotonin and norepinephrine synapses – Consistent with drug effects – MAOIs, SSRIs, SNRIs and tricyclics are all agonists for S and NE. – Depression untreated with drugs may result in proliferation of monoamine receptors (up-regulation), providing support for the monoamine theory • Problem with theory – not all (P)depression respond to monoamine agonists Copyright © Pearson Education 2011 Diathesis-Stress Model of Depression • Diathesis = genetic susceptibility • Diathesis + stress = depression • Early exposure to stress sensitizes a person to overreact to mild stressors the rest of their life • Support is indirect: depressed people… – tend to release more stress hormones – Evidence of early stressors is based on patient recollections and these cannot be confirmed Copyright © Pearson Education 2011 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 60% showed substantial improvements and 35% became symptom free. Copyright © Pearson Education 2011 Anxiety Disorders • Anxiety – Chronic fear in the absence of threat • Anxiety disorder – when anxiety interferes with normal functioning • Accompanied by physiological symptoms of anxiety – tachycardia, hypertension, sleep disturbances, nausea, etc. • The most prevalent psychiatric disorders • Highly treatable Copyright © Pearson Education 2011 Five Classes of Anxiety Disorders • Generalized anxiety disorders – Free floating stress and anxiety in the absence of a causal stimulus • Phobic anxiety disorders – Similar to generalized, but triggered by a particular stimulus (thunder, spiders, heights, flying) • 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 (counting, checking, cleaning, ordering) • Posttraumatic stress disorder – Pattern of psychological distress following exposure to extreme stress (victim of violent crime, war etc.) Copyright © Pearson Education 2011 Etiology of Anxiety Disorders • Good evidence for a genetic contribution (30 – 40%) • Role of life experiences is also critical (obviously, as most are triggered by some object or situation). Copyright © Pearson Education 2011 Pharmacological Treatment of Anxiety Disorders • Benzodiazepines (Librium, Valium) • Also used as hypnotics (sleep inducing), anticonvulsants, muscle relaxants • GABAA agonists – bind to receptor and facilitate effects GABAA Agonist • Serotonin agonists (buspirone, SSRI) Reduce anxiety without sedation, side effects • Antidepressants – effective due to comorbidity of anxiety and depression Copyright © Pearson Education 2011 Neural Basis 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 (one study) Copyright © Pearson Education 2011 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 © Pearson Education 2011 Clinical Trials: Development of New Psychotherapeutic Drugs Copyright © Pearson Education 2011