1. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neuroscience: Exploring the Brain, 3e Chapter 22: Mental Illness

2. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mental Illness and the Brain Mental illness –Diagnosable disorder of thought, mood, or behavior that causes distress or impaired functioning –Earlier belief Disorders of the body Disorders of the mind

3. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mental Illness and the Brain Biological Approaches to Mental Illness –Infection-related disease e.g., ‘general paresis of the insane’ Symptoms: Mania, cognitive deterioration Cause: T. pallidum infection –Penicillin (1928) –Mental illnesses traced directly to biological causes –Roots of mental disorders

4. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Fear –An adaptive response to threatening situations –Innate and species-specific –Learned Anxiety disorders –Characterized by inappropriate expression of fear

5. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Common Anxiety Disorders –Panic disorder –Agoraphobia –Obsessive-compulsive disorder –Generalized anxiety disorder –Specific phobias –Social phobia –Post-traumatic stress disorder

6. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Biological Bases of Anxiety Disorders –Fear evoked by threatening stimulus: Stressor –Manifested by stress response –Stimulus-response relationship strengthened (and weakened) by experience –Stress: Corticotropin-releasing hormone (CRH)  adrenocorticotropic hormone (ACTH)  cortisol

7. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Biological Bases of Anxiety Disorders (cont’d) –Stress Response Cortisol release & sympathetic activation

8. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Regulation of the HPA Axis by the Amygdala and Hippocampus –Both regulate CRH neurons Amygdala projects to bed nucleus of the stria terminalis, which activates the HPA axis Hippocampus deactivates the HPA axis Glucocorticoid receptors Feedback loop –Push-pull style regulation

9. 9 Hippocampus Glucocorticoid (Cortisol) release Hypothalmic CRF release Pituitary, ACTH Adrenal glands Stress Negative feedback Stress response: negative feedback via hippocampus Amygdala

10. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Treatments for Anxiety Disorders –Psychotherapy –Anxiolytic Medications –Role of GABA –Benzodiazepines –Serotonin-selective reuptake inhibitors (SSRIs) –Drug target: CRH receptors (at hypothalamus)

11. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders A Description of Affective Disorders –“Mood” Disorders – Depression Major Depression Dysthymia (less severe) –Bipolar Disorder Manic-depressive disorder Mania (type I) or hypomania (type II)

12. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Biological Bases of Affective Disorders –The Monoamine Hypothesis Problems with diffuse modulatory systems Reserpine (depletes MAs) Monoamine Oxidase (MAO) Imipramine (reuptake inhib) Monoamine hypothesis of mood disorders

13. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Biological Bases of Affective Disorders (cont’d) –The Diathesis-Stress Hypothesis Genetic and nongenetic Diathesis (predispositions) HPA system- Convergence site; genetic and environ. Impact of CRH on HPA function  Role of early experience in shaping stress response Glucocorticoid receptors and influence of Tactile stimulation in rats

14. 14 Maternal care: Licking & grooming pups 5HT release NGFi transcript. factor Hippocampus Glucocorticoid receptors Glucocort. release Hypothalmic CRF release Pituitary, ACTH Adrenal glands Stress Negative feedback Chromatin remodeling (DeMethylation of NGFi binding site) Adult ‘memory’ of maternal care Long-term up regulation of GC mRNA expression cAMP, PKA Epigenetic imprinting: Stress response

15. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Treatments for Affective Disorders –Electroconvulsive Therapy (ECT): Localized electrical stimulation –Advantage of ECT: Quick relief –Adverse effect of ECT: Prior memories, storage of new information –Structures involved: Temporal lobe –Psychotherapy: Help patients overcome negative views

16. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Treatments for Affective Disorders (cont’d) –Antidepressants

17. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Anxiety Disorders Treatments for Affective Disorders –Lithium

18. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Schizophrenia A Description of Schizophrenia –Severe mental disorder –Symptoms of schizophrenia: Loss of contact with reality –Three types of schizophrenia Paranoid schizophrenia Disorganized schizophrenia Catatonic schizophrenia

19. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Schizophrenia Biological Bases of Schizophrenia –Genes and the Environment Schizophrenia: genetic predispositions Schizophrenia and the ventricle to-brain-size ratio Other structural observation of the brains of schizophrenics –The Dopamine Hypothesis: Psychotic episodes in schizophrenia triggered by activation of dopamine receptors –Neuroleptic drugs

20. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Schizophrenia Biological Bases of Schizophrenia (cont’d) –The Glutamate Hypothesis Behavioral effects of phencyclidine (PCP) Introduced in1950s as an anesthetic Inhibits NMDA receptors –Glutamate: Fast excitatory neurotransmitter in the brain, two important receptor subtypes, AMPA and NMDA

21. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Schizophrenia Treatments for Schizophrenia –Consists of drug therapy combined with psychosocial support –Conventional neuroleptics, such as chlorpromazine and haloperidol, act at D2 receptors Reduce the positive symptoms of schizophrenia Also have numerous side effects –NMDA receptor

22. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Concluding Remarks Impact of neuroscience on psychiatry Causes of mental illness still unclear, despite knowing how chemical synaptic transmission is affected by drugs Genes and environment play an important role Environmental stresses may contribute to schizophrenia Appropriate sensory stimulation in early childhood

23. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins End of Presentation

24. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mental Illness and the Brain Human behavior –Product of brain activity Brain –Product of two mutually interacting factors DNA –Determines individualism

25. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mental Illness and the Brain Psychosocial Approaches to Mental Illness –Freud’s theory: Mental illness- Unconscious and conscious elements of psyche come into conflict –Skinner: Many behaviors are learned responses to the environment –Maladaptive behavior

26. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Introduction Neurology –Branch of medicine concerned with the diagnosis and treatment of nervous system disorders Neurological disorders –Help illustrate the role of physiological processes in normal brain function Psychiatry –Branch of medicine concerned with the diagnosis and treatment of disorders that affect the mind or psyche Psychiatric disorders –Examples: Anxiety disorders, affective disorders, schizophrenia