Chapter 22: Mental Illness Neuroscience: Exploring the Brain, 4e Chapter 22: Mental Illness

Introduction Neurology Branch of medicine concerned with the diagnosis and treatment of nervous system disorders Neurological disorders Ranging from multiple sclerosis to aphasia Help illustrate the role of physiological processes in normal brain function

Introduction—(cont.) Psychiatry Branch of medicine concerned with the diagnosis and treatment of disorders that affect the mind or psyche Psychiatric disorders Anxiety disorders Affective disorders Schizophrenia

Mental Illness and the Brain Human behavior Product of brain activity Brain Product of two mutually interacting factors Heredity Environment DNA determines individualism. Health and illness along continuum of bodily function

Mental Illness and the Brain—(cont.) Diagnosable disorder of thought, mood, or behavior that causes distress or impaired functioning Earlier belief Disorders of the body Disorders of the mind Current belief Most disorders of mood, thought, and behavior have biological explanations.

Psychosocial Approaches to Mental Illness Freud’s theory: mental illness: unconscious and conscious elements of psyche come into conflict Treat by unearthing hidden secrets of unconscious Skinner: Many behaviors are learned maladaptive responses to the environment. Treat by “unlearning” through behavior modification Psychosocial approaches to mental illness have sound neurobiological basis. Psychotherapy

Biological Approaches to Mental Illness Former major disorder: general paresis of the insane Symptoms: mania, cognitive deterioration Cause: infection with Treponema pallidum Paul Ehrlich (1910) discovered treatment. Penicillin (1928) treatment Other mental illnesses traced directly to biological causes. Examples: vitamin deficiency, HIV in brain, autoimmune response

Molecular Medicine in Psychiatry Using genetic information to develop treatment Discovery of pathophysiology—may suggest biological processes Target with drug therapy Unique challenges of brain diseases Same diagnosis may arise from many causes. Genetic complexity New approach: study the pathophysiology of neurons

Molecular Medicine

Anxiety Disorders Fear Adaptive response to threatening situations Many fears innate and species-specific. Other fears learned Anxiety disorders Caused by inappropriate expression of fear Most common of psychiatric disorders

Common Anxiety Disorders Panic disorder Agoraphobia Generalized anxiety disorder Specific phobias Social phobia

Other Disorders Characterized by Increased Anxiety Post-traumatic stress disorder Symptoms Increased anxiety Intrusive memories, dreams, or flashbacks Irritability, emotional numbness Obsessive-compulsive disorder Obsessions: recurrent, intrusive thoughts, images, ideas, or impulses Compulsions: repetitive behaviors to reduce anxiety

Biological Bases of Anxiety Disorders Genetic predisposition for many anxiety disorders Fear evoked by threatening stimulus: stressor Manifested by stress response Stimulus–response relationship strengthened (or weakened) by experience Stress response Humoral response: corticotropin-releasing hormone (CRH)  adrenocorticotropic hormone (ACTH)  cortisol

Hypothalamic-Pituitary-Adrenal Axis

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 regulation

Location of Amygdala and Hippocampus

Push–Pull Regulation of the HPA Axis

Treatments for Anxiety Disorders Psychotherapy Anxiolytic medications Role of GABA Benzodiazepines Serotonin-selective reuptake inhibitors (SSRIs) Target for new drugs: CRH receptors

The Action of Benzodiazepine

Affective Disorders “Mood” disorders Recurrent depression Major depression Dysthymia Bipolar disorder, or manic-depressive disorder Recurrent, repeated episodes Type I: mania Type II: hypomania

Biological Bases of Affective Disorders The monoamine hypothesis Deficit in central diffuse modulatory systems Studied by effects of drugs Reserpine Monoamine oxidase (MAO) inhibitors Imipramine Monoamine hypothesis of mood disorders Treatment focus on central serotonergic and/or noradrenergic synapses

Diffuse Modulatory Systems Implicated in Affective Disorders

Biological Bases of Affective Disorders—(cont.) The diathesis-stress hypothesis Genetic predisposition (diathesis), other stress factors Role of HPA axis Impact of CRH HPA function becomes hyperactive. Glucocorticoid receptor gene expression regulated by early experience.

Anterior Cingulate Cortex Dysfunction Resting-state metabolic activity in anterior cingulate cortex increased in depression.

Treatments for Affective Disorders Electroconvulsive therapy (ECT): localized electrical stimulation Unknown mechanism in relieving depression Affects temporal lobe Advantage: quick relief of depression, mania Adverse effect: loss of prior memories, impaired storage of new information Psychotherapy: Help patients overcome negative views. Effective for mild to moderate depression

Treatments for Affective Disorders—(cont.) Antidepressants: MAO inhibitors, tricyclics, and SSRIs

Treatments for Affective Disorders—(cont.) Lithium treatment for bipolar disorder

Deep Brain Stimulation When severe depression fails to respond to other treatment Electrode implanted deep in the brain Region of anterior cingulate cortex (Brodmann’s area 25) Electrical stimulation  decrease activity in brain circuits that are chronically overactive Immediate relief from depression Preliminary findings, brain surgery a treatment of last resort

Schizophrenia Severe mental disorder—loss of contact with reality Positive symptoms Delusions, hallucinations Disorganized speech Grossly disorganized or catatonic behavior Negative symptoms Reduced expression of emotion, poverty of speech Difficulty initiating goal-directed behavior Memory impairment

Biological Bases of Schizophrenia Primarily a genetic disorder Faulty genes  vulnerability to environmental factors Associated with physical changes in the brain Larger ventricle-to-brain size ratio Other important physical changes in brain The dopamine hypothesis: psychotic episodes triggered by activation of dopamine receptors Neuroleptic drugs—potent blockers of dopamine receptors

Dopaminergic Diffuse Modulatory Systems of the Brain

Biological Bases of Schizophrenia—(cont.) The glutamate hypothesis Observed behavioral effects of phencyclidine (PCP) and ketamine Neither affects dopaminergic transmission. Both affect synapses that use glutamate as a neurotransmitter. Inhibit NMDA receptors Hypothesis: Schizophrenia reflects diminished activation of NMDA receptors in the brain.

Blocking of the NMDA Receptor by PCP

Treatments for Schizophrenia Drug therapy combined with psychosocial support Conventional neuroleptics, such as chlorpromazine and haloperidol, act at D2 receptors Reduce the positive symptoms of schizophrenia Numerous side effects Like symptoms of Parkinson’s disease Tardive dyskinesia Newest focus of drug research  NMDA receptor

Concluding Remarks Impact of neuroscience on psychiatry Mental illness recognized as pathologic modifications of the brain Genes and environment play an important role, causes not fully understood. Chemical synaptic transmission is affected by drugs. Unclear why therapeutic drug effects take weeks. Less known about how psychosocial treatments act on the brain.