Lecture 16 (Cut off for Exam 4) Flashcards
Depression/Mania/SCZ
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
Q
SCZ Complexity
A
- Combination of positive, negative, mood, and cognitive symptoms
- Comorbid substance abuse
- Combinations of these lead to disruptive everyday life (social and occupational)
26
Q
SCZ Etiology
A
- Remains unknown, many theories
1. Neurodevelopmental - fetal, childhood, adolescence, teens)
2. Neurodegenerative - Progression over lifetime?
3. Genetic Susceptibility - Multiple Alleles
27
Q
SCZ + Genetics
A
- 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
Q
Neurodevelopment Hypothesis of SCZ
A
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
Q
Neurodegenerative Hypothesis of SCZ
A
- 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
Q
Glutamate + SCZ
A
- 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
Q
SCZ + Lesions
A
- 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
Q
SCZ + Surroundings
A
- 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
Q
Course of Illness
A
- 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
Q
Neurochemical Circuits
A
- Potential therapeutic sites for antipsychotic drugs
- Dopamine neurons in ventral tegmental area project nucleus accumbens which stimulate DA2 receptor
35
Q
Dopamine Agonism
A
Stimulant, Cocaine & Amphetamine
36
Q
Dopamine D2 Antagonist
A
First Generation (Haloperidol)
37
Q
D2 & 5-HT Antagonist
A
Second Generation (Olanzapine, Risperidone, Quetiapine, Ziprasidone)
38
Q
Dopamine Theory of Psychoses
A
- Psychoses is due to excessive dopamine activity in brain from things like cocaine, amphetamine, levodopa, and increased DA in brain
- DA antagonists are clinically effective antipsychotics
39
Q
Dopamine Regulation in SCZ & Antagonists
A
- Mesolimbic pathway - hyperactivity of DA neurons causes positive symptoms. Therapeutic D2 blockade
- Mesocortical pathway - negative symptoms, cognitive effects, increased DA levels. Therapeutic DA2 receptor blockers
- Nigrostriatal Pathway - regulates motor movement, side effects = pseudoparkinson
- Tuberoinfundibular pathway - regulates prolactin release, side effect = hyperprolactinemia
40
Q
SCZ Treatment Options
A
- First Generation Antipsychotics (FGA) - typical antipsychotics, conventional agents, neuroleptics
- Second Generation Antipsychotics (SGA) - atypical antipsychotics
ALL ARE DOPAMINE D2 RECEPTOR ANTAGONISTS
41
Q
D2 Receptor Antagonism + SCZ
A
- 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
Q
First Generation Antipsychotics
A
- Phenothiazine - Chlorpromazine (Thorazine)
- Non-phenothiazine - Haloperidol (Haldol)
- D2 antagonist to decrease positive symptoms of SCZ
43
Q
FGA Side Effects
A
- Extrapyramidal Symptoms - block of striatal D2 receptors which leads to acute dystoria (involuntary movement), pseudoparkinsons, Tardive dyskinesia (involuntary movements long term)
- Prolactin Increase - lactation and breast swelling
- Other - antihistamine, anticholinergic (dry mouth, constipation, tachycardia), sedation, weight gain
44
Q
Second Generation Antipsychotics
A
- 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
Q
Are Antipsychotics only used for SCZ?
A
No, they have many uses. SCZ, bipolar disorder, plus others.
46
Q
SGA Beneficial Therapeutic Effects (3)
A
- Treats negative and positive symptoms (increased efficacy)
- Decrease in extrapyramidal side effects and tardive dyskinesia
- Less prolactin elevation
47
Q
SGA Side Effects (3)
A
- Weight gain - longer treatments lead to more weight gain
- Diabetes Mellitus - increased with long term treatment and may be related to weight gain
- Increased cholesterol levels up to 10% in a short amount of time with some drugs
48
Q
SGA + Cholesterol Levels
A
- Olanzapine - high likelihood of side effect
- Quetiapine & Risperidone - Moderate likelihood
- Abilify - low to no side effect
49
Q
How to choose between SGA & FGA?
A
Depends on which symptoms one is trying to prevent and which side effects one is trying to avoid.
