1. The Drug Revolution for Mental Health
Medicine for Madness

2. Demonic Possession
St. Zenobius exorcises devils (seen fleeing from the mouths of the possessed)

3. A hole in the head: Trepannation

4. Benjamin Rush
( )
Treated mentally ill at Pennsylvannia hospital
Madness as disease
Used talk therapy
Humane treatment
Holistic approach

5. Phillipe Pinel (1745-1826) “Treatise on Insanity” 1791
Removed chains from mental ill patients at Paris asylum (1792)

6. Pinel freeing patients

7. Dorothea Lynde Dix (1802-1887) Found mentally ill housed in jails (MA)
Helped found hospitals in 15 states & Canada
Humane care
Supervised nursing corp: US Civil War

8. Early Treatment The spinning chair One of Rush’s invention
Treatments not very effective

9. Early 20th century treatments
Insulin coma
Lobotomy
First generation “shock” treatment
Restraints
Restrictions
Warehousing
State hospitals growing every year

10. Deinstitutionalization
KW 6-9

11. Mental health movement
Move patients to less restrictive environments (out of state hospitals)
Follow up with community mental health
Monitor continued drug treatment
Patient rights
Change in commitment laws

12. Drug can Modify
KW 6-5

13. Mood Disorders Mood Disorders Major Depressive Disorder
characterized by emotional extremes
Major Depressive Disorder
no apparent reason,
experiences two or more weeks of depressed moods,
feelings of worthlessness, and
diminished interest or pleasure in most activities

14. Depression Major Depressive Disorder
Defined-long-term sadness and helplessness
Demographics
Observed more often in women than men
Peak frequency between 25 and 44
About 19% of all people suffer a bout of depression at least once in their lives
Genetics
Depression does have a genetic link
Gene has not been located

15. Gender Differences in Depression
Age in Years
10% 8 6 4 2
Percentage
depressed
Females
Males

16. Mood Disorders- Suicide
Suicides per
100,000 people 70 60 50 40 30 20 10
Males
Females
The higher suicide rate
among men greatly
increases in late
adulthood

17. Depression Reactive Related to traumatic life event
Can be triggered by an event (ex: death of a loved one, birth of a child, etc)
Endogenous
Source from within
More likely to be related to neurochemical differences

18. Depression Physiology of Depression Two Conclusions
Mood depends on the effects of a combination of transmitters
Different depressed people have somewhat different transmitter abnormalities
Video

19. Mood Disorders-Depression
Altering any one component of the chemistry-cognition-mood circuit can alter the others
Brain
chemistry
Cognition
Mood

20. Tricyclics-prevent reuptake of serotonin or norepinephrine/epinephrine
Depression
Drug Treatments
Antidepressants
Tricyclics-prevent reuptake of serotonin or norepinephrine/epinephrine
MAO Inhibitors-block MAO from breaking down serotonin and norepinephrine/epinephrine
SSRI’s-Selective Serotonin Reuptake inhibitor: inhibits reuptake of serotonin

21.  Routes of action of antidepressants Tricyclics block the reuptake of dopamine, norepinephrine, or serotonin. SSRIs specifically block the reuptake of serotonin. MAOIs block the enzyme MAO, which converts dopamine, norepinephrine, or serotonin into inactive chemicals.

22. Serotonin and Depression
KW 6-11

23. Prozac

24. MDMA Casues Cell Damage
MDMA Changes the density of serotonin axons in monkeys
Normal brain on left
Brain on right 18 months following treatment

25. Depression: Other treatments
ECT
Applied every other day for two weeks
Muscle relaxants and anesthetics minimize discomfort
Memory loss can be a side-effect (limited if shock is given to right hemisphere only
Altered Sleep Patterns
Treat patient like someone with difficulty adjusting to changing time zones

26. Biomedical Therapies
Electroconvulsive Therapy

27. Seasonal Affective Disorder
Defined-depression that regularly recurs in a particular season
Usually treated by bright light therapy

28. Mood Disorders Manic Episode Bipolar Disorder
a mood disorder marked by a hyperactive, wildly optimistic state
Bipolar Disorder
alternates between the hopelessness of depression and the overexcited state of mania
formerly called manic-depressive disorder

29. Bipolar Disorder Defined-alternate between mania and depression
Demographics
May last only days or for a year or more
1% of people have a mild case at some time in life
Average age of onset is early 20’s
Genetics
Concordance rate is .50
No specific gene has been identified

30. Mood Disorders-Bipolar
PET scans show that brain energy consumption rises and falls with emotional swings
Depressed state
Manic state

31. Bipolar Disorder Treatments Lithium Stabilizes mood Mechanism unknown
Side effect: toxicity
Anticonvulsant drugs (like Depakote)
Mechanism of action on cortex (lower activity)

32. Schizophrenia Definitions
literal translation “split mind”
a group of severe disorders characterized by:
disorganized and delusional thinking
disturbed perceptions

33. Schizophrenia Symptoms
Delusions
false beliefs, often of persecution or grandeur, that may accompany psychotic disorders
Hallucinations
false perceptual experiences such as seeing something without any external visual stimulus

34. Prevalence
Schizophrenia affects about 1% of the population and range in severity.
Occurs in all parts of the world, but is 10 to 100 times more common in the United States and Europe than in third-world countries.
More common in men than in women by a ration of about 7 to 5.
More severe and earlier age of onset for men (early 20’s versus late 20).
Likelihood increases as the age of the father increases.

35. Characteristics of Schizophrenia
Deteriorating ability to function
Accompanied by delusions, hallucinations, thought disorder, movement disorder and inappropriate emotional expression
Behavioral Symptoms
Positive Symptoms-behavior that are present that should be absent
Delusions, hallucinations, thought disorders
Negative Symptoms-behavior that is absent that should be present
Weak social interactions, emotional expression, speech, and working memory

36.  Probabilities of developing schizophrenia The closer the genetic relationship to someone with schizophrenia, the higher the probability of developing it oneself.

37. Schizophrenia and Genetics
Concordance rate is 50%
However, genes are not the only influence
A gene has not been located for schizophrenia

38. Hypotheses of Causation in Schizophrenia
Neurodevelopmental
Either genes or difficulties early in life impair brain development in ways that lead to schizophrenic-like symptoms in early adulthood
Dopamine Hypothesis-Excess dopamine activity causes behavioral changes associated with schizophrenia
Supported by drug treatments that target dopamine
Glutamate Hypothesis-the problem is deficient glutamate activity

39. Neurodevelopmental
The neurodevelopmental hypothesis suggests abnormalities in the prenatal or neonatal development of the nervous system.
Leads to subtle abnormalities of brain anatomy and major abnormalities in behavior.
Abnormalities could result from genetics, difficulty during birth, or a combination of both.

40. Causation
Supporting evidence for the neurodevelopmental hypothesis includes:
Several kinds of prenatal or neonatal difficulties are linked to later schizophrenia.
People with schizophrenia have minor brain abnormalities that originate early in life.
Abnormalities of early development could impair behavior in adulthood.

41. Prenatal Risk Factors
Prenatal risk factors increasing the likelihood of schizophrenia include:
Poor nutrition of the mother during pregnancy.
Premature birth.
Low birth weight.
Complications during delivery.
Head injuries in early childhood are also linked to increased incidence of schizophrenia.

42. Season of Birth
Certain viral infections may be an alternative or supplement genetic influences.
The seasoned-of-birth effect refers to the tendency for people born in winter to have a slightly (5% to 8%) greater probability of developing schizophrenia.
More pronounced in latitudes far from the equator.
Might be explained by complications of delivery, nutritional factors, or increased likelihood of viral infections

43. Schizophrenia and Brain
Schizophrenia is associated with mild brain abnormalities:
Strongest deficits found in the left temporal and frontal lobe of the cortex.
Larger than normal ventricles.
Especially common in those with complications during birth.
Areas that mature slowly such as the dorsolateral prefrontal cortex.
Schizophrenics have deficits in working memory.

44. MRI Scans of Schizophrenia
Normal Twin Schizophrenic Twin
MRI Scans of Schizophrenia

45. CBF in Schizophrenia

46. Treatment
Antipsychotic/neuroleptic drugs are drugs that tend to relieve schizophrenia and similar conditions.
Chlorpromazine (thorazine) is a drug used to treat schizophrenia that relieves the positve symptoms of schizophrenia.
Relief usually experienced 2-3 weeks after taking the drug, which must be taken indefinitely.

47. Schizophrenia Treatment
Antipsychotic Drugs-All block postsynaptic dopamine receptors
First Generation Antipsychotics (FGA’s)
Phenothiazines-chlorpromazine
Butyrophenones-haloperidol

48. Dopamine and Psychosis
KW 6-10

49. Antipsychotics

50. Dopamine hypothesis
The dopamine hypothesis of schizophrenia suggests that schizophrenia results from excess activity at dopamine synapses in certain areas of the brain.
Substance-induced psychotic disorder is characterized by hallucinations and delusions resulting from repeated large doses of amphetamines, methamphetamines, or cocaine.
Each prolongs activity of dopamine at the synapse, providing further evidence for dopamine hypothesis.

51. Pathways affected
The mesolimbocortical system is a set of neurons that project from the midbrain tegmentum to the limbic system.
Site where drugs that block dopamine synapses produce their benefits.
Drugs also block dopamine in the mesostriatal system, which project to the basal ganglia.
Result is tardive dyskinesia, characterized by tremors and other involuntary movements.

52. Fig. 15-20, p. 479 Figure 15.20: Two major dopamine pathways.
Overactivity of the mesolimbocortical system is linked to the symptoms of schizophrenia; the path to the basal ganglia is associated with tardive dyskinesia, a movement disorder. (Source: Adapted from Valzelli, 1980)
Fig , p. 479

53. SGA’s
Second-generation antipsychotics (atypical antipsychotics) are a class of drugs used to treat schizophrenia but seldom produce movement problems.
Examples: clozapine, risperidone.
More effective at treating the negative symptoms and are now more widely used.
Have less effect on dopamine D2 receptors and more strongly antagonize serotonin type 5-HT2 receptors.

54. TGA’s? Third Generation Antipsychotics. Abilify® (aripiprazole)
Act on both dopamine and serotonin.
Regulates, rather than blocks, dopamine.
May help both positive and negative symptoms.
Side effects: restlessness, constipation, sleepiness, involuntary movement.

55. Schizophrenia Conclusions
Schizophrenia cannot be explained by a single gene or single transmitter.
Dopamine and glutamate may play important roles in schizophrenia to different degrees in different people.
Schizophrenia involves multiple genes and abnormalities in dopamine, glutamate, serotonin and GABA.