Slide 1

Slide 2

The Drug Revolution for Mental Health Medicine for Madness

Slide 3

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

Slide 4

A hole in the head: Trepannation

Slide 5

Benjamin Rush (1745-1813) Treated mentally ill at Pennsylvannia hospital Madness as disease Used talk therapy Humane treatment Holistic approach

Slide 6

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

Slide 7

Pinel freeing patients

Slide 8

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

Slide 9

Early Treatment The spinning chair One of Rushs invention Treatments not very effective

Slide 10

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

Slide 11

Deinstitutionalization KW 6-9

Slide 12

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

Slide 13

Drug can Modify KW 6-5

Slide 14

Mood Disorders 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

Slide 15

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

Slide 16

Gender Differences in Depression 12-17 18-24 25-34 35-44 45-54 55-64 65-74 75+ Age in Years 10% 8 6 4 2 0 Percentage depressed Females Males

Slide 17

Mood Disorders- Suicide 15-24 25-34 35-44 45-44 55-64 65-74 75-84 85+ Suicides per 100,000 people 70 60 50 40 30 20 10 0 Males Females The higher suicide rate among men greatly increases in late adulthood

Slide 18

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

Slide 19

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

Slide 20

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

Slide 21

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

Slide 22

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.

Slide 23

Serotonin and Depression KW 6-11

Slide 24

Prozac

Slide 25

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

Slide 26

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

Slide 27

Biomedical Therapies Electroconvulsive Therapy

Slide 28

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

Slide 29

Mood Disorders Manic Episode 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

Slide 30

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 20s Genetics Concordance rate is.50 No specific gene has been identified

Slide 31

Mood Disorders-Bipolar PET scans show that brain energy consumption rises and falls with emotional swings Depressed stateManic stateDepressed state

Slide 32

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

Slide 33

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

Slide 34

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

Slide 35

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 20s versus late 20). Likelihood increases as the age of the father increases.

Slide 36

Characteristics of Schizophrenia Characteristics 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

Slide 37

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

Slide 38

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

Slide 39

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

Slide 40

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.

Slide 41

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.

Slide 42

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.

Slide 43

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

Slide 44

Schizophrenia and Brain S chizophrenia 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.

Slide 45

MRI Scans of Schizophrenia Normal Twin Schizophrenic Twin

Slide 46

CBF in Schizophrenia

Slide 47

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.

Slide 48

Schizophrenia Treatment Antipsychotic Drugs-All block postsynaptic dopamine receptors First Generation Antipsychotics (FGAs) Phenothiazines-chlorpromazine Butyrophenones-haloperidol

Slide 49

Dopamine and Psychosis KW 6-10

Slide 50

Antipsychotics

Slide 51

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.

Slide 52

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.

Slide 53

Fig. 15-20, p. 479

Slide 54

SGAs 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 D 2 receptors and more strongly antagonize serotonin type 5-HT 2 receptors.

Slide 55

TGAs? 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.

Slide 56

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.