Lecture 16 (Cut off for Exam 4) Flashcards
Depression/Mania/SCZ (49 cards)
1
Q
Major Unipolar Depression
A
- Changes in mood
- Not related to life experiences usually
- Cannot experience pleasure, loss of interest in normal activities, insomnia, loss (or sometimes gain) of appetite
2
Q
Unipolar Depression Screening
A
SALSA S - Sleep disturbance (insomnia with 2-4 AM waking) A - Anhedonia LS - Low Self Esteem A - Appetite Decreased
3
Q
Mania
A
- Elevated euphoria, self esteem, and grandiosity
- Restlessness with high energy and activity levels
- Hypomania = less severe form of mania
4
Q
Manic-Depression Disorder
A
- Aka Bipolar Disorder
- Bipolar I - Mania and major depression
- Bipolar II - Hypomania and major depression
- Cyclothymic - Hypomania and mild to moderate depression
- Dysthymic - Mild to moderate depression most of the time with not discrete episodes
5
Q
Monoamine Theory of Depression
A
- Depression due to lack of 5-HT (Serotonin) and NE
- Reserpine depletes biogenic amines and induces depression
- B-Blockers have high lipid solubility and cause depression as a side effect
6
Q
Effective Antidepressants
A
Increase 5-HT or NE Levels
- TCA
- SSRI
- MAOI - Monoamine Oxidase Inhibitors
- Drugs that increase 5-HT or NE release
Require 2-6 weeks of chronic treatment to reap the benefits
7
Q
Neurogenesis Theory of Depression
A
- Stress-induced decrease of hippocampal neurogenesis that leads to depression
- Increased neurogenesis via antidepressants can take weeks
- Stress, genetics, and growth factors all effect this
8
Q
BDNF
A
Neuropeptide that regulates growth, survival, and differentiation of neurons for synaptic plasticity
9
Q
Depression Facts
A
- Affects ~19 million Americans
- Affects women more than men
- Genetics - you are 2-3x more likely to develop depression if a close relative also has depression
- 76% of identical twins both had depression in a study
- About 50% of those with bipolar disorder have a clinically depressed parent
10
Q
Antidepressants (6)
A
- TCA - Amitriptyline (Elavil)
- SSRI - Similar efficacy and better side effect profile, Citalopram, Sertraline, Fluoxetine, Lexapro, Paxil
- SNRI - similar efficacy, Atomoxetine (Strattera), Venlafaxine, Duloxetine
- MAOI - tyramine interaction, do not combine with TCA or SSRI. Phenylzine (Nardil)
- Increase 5-HT or NE levels - Trazodone & Mirtazapine
- Electroconvulsive Therapy - most rapid and effective in severe, suicidal depression
11
Q
Mood Stabilizers for Bipolar Disorder (3)
A
- Lithium - prevents manic and depressive phases
- Anticonvulsants - Gabapentin, Topiramate, Lamotrigine, Valproic Acid (Depakote)
- Antipsychotics - Quetiapine, Risperidone, Abilify, Olanzapine (Zyprexa)
12
Q
Psychoses
A
- Disorders of Thought
- Impaired behavior with inability to think coherently or comprehend reality
- May include hallucinations and delusions
- Most telling symptom is “lack of insight”
- People are unaware that they are acting unusually not matter how outrageous their delusion may be
- Lack of insight varies from patient to patient and doesn’t occur in everyone
13
Q
Disorders + Psychoses (7)
A
- Brain Damage
- Alzheimer’s Disease
- Bipolar Disorder
- Mania
- Schizophrenia
- Parkinsons on high dose L-DOPA
- Amphetamine and cocaine psychoses
14
Q
Best Psychoses Treatment
A
- Antipsychotics
- Best choice no matter what the cause may be
- May need to use in conjunction with antidepressant, anticonvulsants, or other drugs
15
Q
Drug Induced Psychoses
A
- Causes from overstimulation of brain by stimulants (amphetamine or cocaine)
- Can experience excitation after withdrawal from a strong sedative
- Treat with Benzos, though antipsychotics are also effective
16
Q
Schizophrenia History
A
- Documented back to 3000 BC - possessions and exorcisms, some of which were drilling holes in head
- “Bedlam” hospital in 1330 London held lunatics and you could pay a penny to watch them in their cells (“Show of Bedlam”)
- Dr. Emile Kraepelin - named it a discrete mental illness in 1887, termed “dementia praecox” (early dementia) and believed it to be a disease of the brain
- Term “Schizophrena” coined by Dr. Eugen Bleuler in 1911
17
Q
Schizophrenia Epidemiology
A
- Global prevalence is ~1%
- Men and women have it in equal frequency
- Men show in late teens or early twenties, women show in late twenties or early thirties
- Higher comorbid incidences including hypertension, diabetes, cardiac concern, STDs, smoking etc. with Schizophrenic patients
- Increases the natural causes of death in these patients linked to these other disease states, possibly due to reduced use of medical services, disorganized behavior, or drug therapy utilized
- Mortality is higher in this disease state, 10% incidence of suicide
18
Q
Schizophrenia (SCZ)
A
Characterized by delusions, hallucinations, disorganized speech and behavior, and other symptoms
19
Q
SCZ Diagnosis
A
States by APA - Diagnostic Manual of Mental Disorders
- Disorder lasts at least 6 months
- Includes at least 1 month of active-phase symptoms
- Should have at least two of characterized symptoms
- Subtypes no longer identified
20
Q
Delusions
A
- Erroneous beliefs - involve misinterpretation of perceptions or experiences
- Can be persecutory (tormented, spied on)
- Alien thoughts placed into mind and judged to be bizarre
21
Q
Hallucinations
A
- Auditory is most common
- Voices distinct from person’s own thoughts
- Hearing, seeing, feeling, and smelling something not there
22
Q
Disorganized Speech
A
- Thinking as well
- Conversations or thinking that slips off track
- Loose associations, unrelated, disorganized
23
Q
Grossly Disorganized
A
- Inability to function in society
- Restless, angry, agitated, disheveled, difficulties in daily activities, repeating the same activity
24
Q
Other Negative SCZ Symptoms (Four A)
A
- Affective Flattening - unresponsive face and diminished emotions
- Alogia - poverty of speech, brief & empty replies
- Avolition - inability to initiate/persist in work/social activities
- Anhedonia - without please, inability to experience pleasurable emotions from pleasurable activities
25
SCZ Complexity
- Combination of positive, negative, mood, and cognitive symptoms
- Comorbid substance abuse
- Combinations of these lead to disruptive everyday life (social and occupational)
26
SCZ Etiology
- Remains unknown, many theories
1. Neurodevelopmental - fetal, childhood, adolescence, teens)
2. Neurodegenerative - Progression over lifetime?
3. Genetic Susceptibility - Multiple Alleles
27
SCZ + Genetics
- Risk of SCZ in general population is ~1%
- ~10% if you have a first degree relative with SCZ
- 48% of indentical twin pairs both will have SCZ
**Must be pre/post natal environment, psychosocial, and/or physical environment factors as well**
28
Neurodevelopment Hypothesis of SCZ
Normal Brain Development
- Newborn to adult: about a 50% decrease in neurons
- On average, about 35% of dendrites at two years of age are pruned by mid-adolescence
Possible Development Problems
- Fetal disturbance (infection, hypoxia, etc.) leads to abnormal neuron migration in developing brains
- May be excessive pruning or excessive loss of neurons from start which would explain SCZ development
- Development disturbances may lead to abnormal neuron migration and the pruning may lead to loss of neurons and could produce disorganization
29
Neurodegenerative Hypothesis of SCZ
- Progressive nature of illness - indicates that underlying cause isn't static and previously completed pathological process
- Excessive glutamate stimulation
- May be a combination of theories, so it is recommended to start early, aggressive, sustained treatment from first break to keep disease under control
30
Glutamate + SCZ
- In excessive amounts, glutamate can cause excitotoxicity where the neurons are "excited to death"
- Starts as a normal process, overstimulation of brain leads to first break damage
- Calcium channels remain open and the influx of calcium causes the formation of free radicals that cause toxic actions on organelles and membranes which can lead to cell death
* *NO GLUTAMATE ANTAGONISTS FOR SCZ, ONLY ALZHEIMER'S**
31
SCZ + Lesions
- May be connected to brain disease where lesions form on cortical areas of brain that may exhibit cortical thickness in enlarged ventricles
- Lesions are disorganized neural networks that have fewer neurons and excess loss of cortical gray matter
- Leads to overstimulation of brain, difficulty filtering out extraneous stimuli, and delusions/hallucinations
32
SCZ + Surroundings
- SCZ patients have a decreased capability to filter out unimportant environmental features
- Attention is drawn impulsively and unpredictably to many details that others ignore
- Can lead to misinterpretation of their environment and could cause hallucinations and/or delusions
33
Course of Illness
- Ideal - Initial psychotic episode is quickly detected and treated so that further illness can be prevented by prophylatic treatment
- Chronic Relapsing - Each psychotic exposure decreases global function
34
Neurochemical Circuits
- Potential therapeutic sites for antipsychotic drugs
| - Dopamine neurons in ventral tegmental area project nucleus accumbens which stimulate DA2 receptor
35
Dopamine Agonism
Stimulant, Cocaine & Amphetamine
36
Dopamine D2 Antagonist
First Generation (Haloperidol)
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D2 & 5-HT Antagonist
Second Generation (Olanzapine, Risperidone, Quetiapine, Ziprasidone)
38
Dopamine Theory of Psychoses
1. Psychoses is due to excessive dopamine activity in brain from things like cocaine, amphetamine, levodopa, and increased DA in brain
2. DA antagonists are clinically effective antipsychotics
39
Dopamine Regulation in SCZ & Antagonists
1. Mesolimbic pathway - hyperactivity of DA neurons causes positive symptoms. Therapeutic D2 blockade
2. Mesocortical pathway - negative symptoms, cognitive effects, increased DA levels. Therapeutic DA2 receptor blockers
3. Nigrostriatal Pathway - regulates motor movement, side effects = pseudoparkinson
4. Tuberoinfundibular pathway - regulates prolactin release, side effect = hyperprolactinemia
40
SCZ Treatment Options
- First Generation Antipsychotics (FGA) - typical antipsychotics, conventional agents, neuroleptics
- Second Generation Antipsychotics (SGA) - atypical antipsychotics
**ALL ARE DOPAMINE D2 RECEPTOR ANTAGONISTS**
41
D2 Receptor Antagonism + SCZ
- Correlations between therapeutic potency of antipsychotics and their affinity for D1 or D2 binding
- The higher the affinity the lower the dose and vice versa
42
First Generation Antipsychotics
- Phenothiazine - Chlorpromazine (Thorazine)
- Non-phenothiazine - Haloperidol (Haldol)
- D2 antagonist to decrease positive symptoms of SCZ
43
FGA Side Effects
1. Extrapyramidal Symptoms - block of striatal D2 receptors which leads to acute dystoria (involuntary movement), pseudoparkinsons, Tardive dyskinesia (involuntary movements long term)
2. Prolactin Increase - lactation and breast swelling
3. Other - antihistamine, anticholinergic (dry mouth, constipation, tachycardia), sedation, weight gain
44
Second Generation Antipsychotics
- Olanzapine
- Quetiapine
- Risperidone
- Aripiprazole (Abilify)
-Atypical Antipsychotics and have D2 antagonism to decrease positive symptoms AND 5HT antagonism to decrease negative and cognitive symptoms by increase DA release in cortex
45
Are Antipsychotics only used for SCZ?
No, they have many uses. SCZ, bipolar disorder, plus others.
46
SGA Beneficial Therapeutic Effects (3)
1. Treats negative and positive symptoms (increased efficacy)
2. Decrease in extrapyramidal side effects and tardive dyskinesia
3. Less prolactin elevation
47
SGA Side Effects (3)
1. Weight gain - longer treatments lead to more weight gain
2. Diabetes Mellitus - increased with long term treatment and may be related to weight gain
3. Increased cholesterol levels up to 10% in a short amount of time with some drugs
48
SGA + Cholesterol Levels
- Olanzapine - high likelihood of side effect
- Quetiapine & Risperidone - Moderate likelihood
- Abilify - low to no side effect
49
How to choose between SGA & FGA?
Depends on which symptoms one is trying to prevent and which side effects one is trying to avoid.
