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

2. 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

3. 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

4. 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

5. 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.

6. 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

7. 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

8. 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

9. Molecular Medicine

10. 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

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

12. 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

13. 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

14. Hypothalamic-Pituitary-Adrenal Axis

15. 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

16. Location of Amygdala and Hippocampus

17. Push–Pull Regulation of the HPA Axis

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

19. The Action of Benzodiazepine

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

21. 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

22. Diffuse Modulatory Systems Implicated in Affective Disorders

23. 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.

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

25. 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

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

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

28. 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

29. 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

30. 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

31. Dopaminergic Diffuse Modulatory Systems of the Brain

32. 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.

33. Blocking of the NMDA Receptor by PCP

34. 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

35. 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.