Neuroscience Exploring the Brain 3 e Chapter 22

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 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 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 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 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anxiety Disorders • Biological Bases of Anxiety Disorders (cont’d) – Stress Response Cortisol release

Role of Amygdala 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Stress response: negative feedback via hippocampus Hippocampus Negative feedback Amygdala Stress Glucocorticoid (Cortisol) release Hypothalmic CRF release Adrenal glands Pituitary, ACTH 10

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

Epigenetic imprinting: Stress response Maternal care: Licking & grooming pups Negative feedback 5 HT release Hippocampus c. AMP, PKA NGFi transcript. factor Glucocorticoid receptors Stress Hypothalamic CRF release Adult ‘memory’ of maternal care Chromatin remodeling (De. Methylation of NGFi binding site) Long-term up regulation of GC m. RNA expression Adrenal glands Pituitary, ACTH Glucocort. release 15

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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anxiety Disorders • Treatments for Affective Disorders (cont’d) – Antidepressants Copyright © 2007 Wolters

Anxiety Disorders • Treatments for Affective Disorders – Lithium Copyright © 2007 Wolters Kluwer

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 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 differences of the brains of schizophrenics – The Dopamine Hypothesis: Psychotic episodes in schizophrenia triggered by activation of dopamine receptors – Neuroleptic drugs (e. g. , chlorpromazine) Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Schizophrenia • Biological Bases of Schizophrenia (cont’d) – The Glutamate Hypothesis • Behavioral effects of phencyclidine (PCP) • Introduced in 1950 s as an anesthetic • ‘Inhibits’ NMDA receptors (open-channel blocker) – Glutamate: Fast excitatory neurotransmitter in the brain, two important receptor subtypes, AMPA and NMDA 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 D 2 receptors • Reduce the positive symptoms of schizophrenia • Also have numerous side effects – NMDA receptor 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

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