Lecture Overview

1. Lecture Overview Schizophrenia Biochemical Bases Neurological Bases Major Affective Disorders Biochemical Bases Seasonal Affective Disorder Anxiety Disorders Panic Disorder Obsessive-Compulsive Disorder

2. Schizophrenia Disorder of thought and emotion Thought disorder Hallucinations Delusions Incidence (about 1%) No gender differences in incidence

3. Symptoms of Schizophrenia Positive symptoms: presence of Delusions (e.g. control, grandeur, persecution) Hallucinations (auditory and olfactory) Thought disorder Negative symptoms: loss of normal behaviors Poverty of speech Low initiative Social withdrawal Diminished affect

4. Heritability of Schizophrenia The biological basis of schizophrenia is evident in heritability studies: Adoption studies Schizophrenics adopted as children are likely to have schizophrenic biological relatives. Twin studies Concordance rates for schizophrenia are higher for identical than for fraternal twins: No single gene identified for schizophrenia

6. Negative Symptoms of Schizophrenia Signs of brain damage Eye tracking problems Catatonia Problems with blinking, eye focusing and pursuit Ventricular enlargement: loss of brain cells Reduced activity of frontal lobes Damage to: Dorsolateral prefrontal cortex Medial temporal lobes

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8. Hypofrontality in Schizophrenia PET scans reveal reduced neural activity within frontal lobes of schizophrenics

10. Factors That May Produce Neurological Damage Birth trauma (obstetrical issues) Viral infections Seasonality effects (schizophrenia is more likely for winter births) Nutritional issues Stress

11. Positive Schizophrenic Symptoms: The Dopamine Hypothesis Chlorpromazine (CPZ) was identified as an effective antipsychotic (AP) agent CPZ was later found to block DA receptors Drugs that block DA receptors vary in AP effectiveness Stimulants such as amphetamine release DA Chronic administration of amphetamine can induce schizophrenia Stimulants can reinstate psychoses in recovered patients

12. DA Activity in Schizophrenia Increased DA levels: some in striatum Increased receptor activity? Postmortem studies suggest increased D2 receptors PET studies suggest no change in D2 receptors in striatum AP drugs may induce observed changes in receptors Are we looking in the right place? (Nuc. accumbens should be examined) Clozapine: may interact with D4 receptors in accumbens

13. Side Effects of Antipsychotic Medication Autonomic problems (dry mouth) Skin-eye pigmentation Breast development (increased prolactin release) Tardive dyskinesia: facial tics and gestures

14. Major Affective Disorders Affect: emotions, moods, and feelings Major affective disorders: Bipolar disorder - alternating cycles of Mania: euphoria, delusions Depression: profound sadness, guilt, suicide risk Unipolar depression: continuous, episodic

15. Biological Bases of Affective Disorder Heritability of AD has been established in twin studies No clear linkage to a single gene Physical treatments for depression Pharmacological treatments MAO inhibitors (e.g. iproniazid) Serotonin reuptake inhibitors (e.g. Prozac) Electroconvulsive shock therapy (ECS) Sleep deprivation

16. Monoamine Hypothesis of Depression Depression results from reduced activity of the monoamines NE or 5-HT Reserpine depletes monoamines--> depression Antidepressants meds increase either NE or 5-HT Via blockade of reuptake Tryptophan deletion procedure: Reduces brain 5-HT levels Reinstates depression in former depression patients Not effective in persons treated with NE reuptake drugs

17. Links Between REM Sleep and Depression Sleep patterns in depressed persons REM deprivation improves mood Antidepressant drugs suppress REM sleep, and increase slow-wave sleep Persons who have short REM sleep latency are more likely to develop depression REM sleep deprivation is more effective than is total sleep deprivation

19. Seasonal Affective Disorder SAD: form of depression evident in winter months (short days/long nights) Mood and sleep disturbances Carbohydrate cravings and weight gain Phototherapy for SAD: increased exposure to light improves mood in SAD (and also in unipolar depression)

20. Anxiety Disorders Panic Disorder: acute intense anxiety Episodes of panic occur in 1-2 % of population Early onset (rare after age 35) Similar symptoms across cultures Concerns about future panic attacks leads to Agoraphobia: fear of panic attack in public places Obsessive-Compulsive (O-C) Disorder Recurrent thoughts and actions

21. Biological Bases of Panic Disorder MZ twins have a higher concordance rate for panic disorder Panic Disorder is more likely in families of patients with the disorder Panic attacks can be triggered by: Lactic acid Caffeine Increased levels of carbon dioxide in air

22. Biological Bases continued Panic Disorder may involve The putative satiety agent CCK CCK4 induces panic attack Serotonin Panic Disorder responds to fluoxetine (5-HT agonist) Panic Disorder is treated via: Behavior therapy Benzodiazepines: agonists alter GABA binding

23. Obsessive-Compulsive Disorder Obsessions: recurrent thoughts Compulsions: recurrent behaviors Incidence of O-C Disorder is 1-2 percent O-C Disorder begins in young adulthood Symptoms of O-C Disorder are similar across differing cultures O-C Disorder can greatly limit life options

24. Compulsions Four categories of compulsions: Counting (�am I missing a dollar?�) Cleaning (hands, house) Checking (�Did I turn the stove off?�) Avoidance (e.g. dirt) Resemble species-typical behaviors Compulsive behaviors are exaggerations of normal species typical behaviors

25. Brain Activity and O-C Disorder Links between neurology and O-C Disorder Tourette�s syndrome: muscular/vocal tics Damage to basal ganglia, cingulate gyrus, and prefrontal cortex Increased activity within the frontal lobes Drug therapy reduces frontal lobe activity Surgical transection of the subcortical frontal lobe leads to improvement in O-C Disorder 22 caliber frontal lobotomy...

26. Pharmacotherapy of O-C Disorder Drug therapy for O-C Disorder 5-HT systems Blockade of 5-HT reuptake improves O-C Disorder Clomipramine Fluoxetine Fluvoxamine Antagonism of 5-HT worsens O-C Disorder 5-HT agonism appears to reduce intensity of the species-typical behaviors (e.g. washing)