Ch.16 Psychopathology Flashcards
Epidemiology
study patterns of disease in a population
Depression is more prevalent in what gender?
Females
Drug dependency is more prevalent in what gender?
Males
Alcoholism is more prevalent in what gender?
Males
Peaks for depression occurs at what age?
25 to 44 years old
Peaks for antisocial behavior occurs at what age?
25 to 44 years old
Cognitive impairment occurs especially in people of what age group?
Older than 65
What percent of the U.S. population report symptoms that match the defining features of a major psychiatric disorder.
33.33% or 1/3rd of the population.
What percent of people with Schizophrenia recover?
30-40%
Why is schizophrenia considered a “public” disorder?
B/c many who have it become homeless on our streets
What is the prevalence of Schizophrenia?
1% which is ~3 million people in the United States.
Dissociative thinking
The key symptom of schizophrenia
major impairment in logical structure and thought.
Key symptom of schizophrenia?
Dissociative thinking
Are Schizophrenia hallucinations usually visual and auditory?
No usually just auditory if some one has a visual hallucination it is usually associated with a drug such as LSP and not a schizophrenic episode.
What are the clinical features common to the varied forms of schizophrenia according to German Psychiatrist Emil Kraepelin?
Paranoia grandiose delusions abnormal emotional regulation (changes in emotion/affect) bizarre disturbances of thought auditory hallucinations
What are the associative symptoms of schizophrenia identified by Eugen Bleuler in his book “The Group of Schizophrenias”?
loosened associations
emotional disturbance
delusions (false thought)
hallucinations (auditory)
What are the clinical features common to the varied forms of schizophrenia according to German Psychiatrist Emil Kraepelin?
Paranoia grandiose delusions abnormal emotional regulation bizarre disturbances of thought auditory hallucinations
What are considered today’s symptoms of schizophrenia?
1) auditory hallucinations
2) Highly personalized delusions (false belief)
3) changes in affect (emotion)
Some investigators proposed major division of schizophrenic symptoms into what two groups?
1) Positive
2) Negative
Examples of positive symptoms in reference to schizophrenia?
hallucinations
delusions
excited motor behavior
The term negative symptoms refers to what
Behavioral functions that have been lost
The term positive symptoms refers to what
abnormal behavioral states that have been gained
What suggest that positive and negative symptoms arise from different neural abnormalities?
Positive and negative symptoms respond differently to drug treatments.
There are several kinds of schizophrenia that vary in related degree of what?
Paranoia, blunted effect, or cognitive impairment.
Role of genes in schizophrenia? All or nothing?
No instead they can simply affect the probability that an individual will develop the disorder.
Examples of negative symptoms in reference to schizophrenia?
slow and impoverished thought slow and impoverished speech emotional withdrawal social withdrawal blunted affect of emotional expression
What is Alogia?
reduced speech output, a negative symptom of schizophrenia
What is the Flat affect?
blunted emotional response, a negative symptom of schizophrenia
What is Anhedonia?
loss of pleasurable feeling, a negative symptom of schizophrenia.
What is Catatonia?
Reduced movement, a negative symptom of schizophrenia.
Is Schizophrenia an inheritable disorder?
it is partially heritable but environmental influences and developmental difficulties also play a role in the development of schizophrenia.
who has a higher risk of schizophrenia than general population?
parents and siblings of people with schizophrenia. Which supports the theory of it being partly genetic since the closer relatives share a greater number of genes.
What do they mean when they say the mode of inheritance of Schizophrenia is not simple?
It means it does not involve a single recessive or dominant gene. Rather multiple genes can play a role in the emergence of schizophrenia.
Monozygotic twins
identical; share an identical set of genes.
what type of monozygotic twins are more likely to be concordant for schizophrenia?
Monozygotic twins that share the same placenta are more likely to be concordant for schizophrenia than monozygotic twins with their own placenta.
Why can one twin with the same genetics have schizophrenia and not the other if schizophrenia partly has to do with genetics?
Genes can be expressed in different ways.
dizogotic twins
fraternal; have 1/2 their genes in common
Concordant for schizophrenia means what?
Concordant refers to when both twins in a pair express/suffer from the trait, in this case the trait being schizophrenia.
Discordant for schizophrenia refers to?
Discordant refers to when only one of a pair of twins suffers from/expresses a trait, in this case the trait being schizophrenia.
what is the percent of monozygotic twins of people with schizophrenia are concordant for the disorder?
~1/2 or 50%
What percent of dizogotic twins of people with schizophrenia are concordant for the trait?
17%
What is strong evidence of the genetic factor of schizophrenia?
The percent of concordant of schizophrenia for monzygotic twins of people with the disorder is significantly higher than the percent concordant for dizogotic twin. Monozygotic zwins are twice as closely related by genetics than dizogotic twins. Also the environmental and variables like family structure and socioeconomic stress factor would be presumably comparable for twins.
What typically tended to be the characteristics of the twin that developed schizophrenia, in twins that were discordant for the trait?
tended to be more abnormal throughout life
frequently weighed less at birth
Early developmental history including more instances of physiological distress.
during development more submissive. tearful, sensitive than the other twin and seen by the parents as more vulnerable.
In childhood impairments of motor control and other neurological signs
behavioral developmental difficulty during childhood
Cognitive development difficulty during childhood
How can an eye tracking measurements (neuropsychological test) show if you may have schizophrenia?
In an eye tracking measurement the eye movements are recorded while the eyes follow a moving target on a computer screen. These measurements are abnormal in schizophrenic patients. Schizophrenic patients tend to be unable to use normal smooth muscle movements of the eyes to follow the moving target and instead show an intrusion of rapid, jerky eye movements.
endophenotype
Behavioral or physical characteristics accompany susceptibility to a particular disorder, which may be used to identify those risks.
Genetic analyzing suggest genes influencing the development of schizophrenia are scattered across many different human chromosomes. However there have been a few genes identified that appear to be abnormal in a substantial proportion of schizophrenic cases. These genes include?
encoding for neuregulin 1 dysbindin catechol-O-meth-yltransferase (COMT) G27 disrupted in schizophrenia 1 (DISC1)
genes encoding for neuregulin 1 participatein?
NMDA, GABA and ACh receptor regulation.
abnormality identified in schizophrenics
dysbindin is a gene implicated in what?
synaptic plasticity
abnormality identified in schizophrenics
catechol-O-meth-yltransferase (COMT) is a gene involved in what?
metabolizing dopamine
abnormality identified in schizophrenics
G27 is a gene thought to contribute to what?
to glutamatergic activity.
Abnormality identified in schizophrenics
How does paternal age play a role in schizophrenia?
Older fathers are more likely than younger men to have children with schizophrenia.
Why may paternal age play a role in schizophrenia?
Perhaps the sperm of older men, which are the product of more cell divisions than the sperm of younger men, have accumulated more mutations by errors in copying the chromosomes; these mutations may increase likelihood of schizophrenia.
what are the ventricular abnormalities in patients with schizophrenia?
Many have enlarged cerebral ventricles especially the lateral ventricles.
How does duration of hospitalization and length of illness affect the size of the ventricles in schizophrenics?
It does NOT affect it at all.
How does ventricular enlargement predict the responsiveness to anti-psychotic drugs?
Patients with more enlarged ventricles tend to show poorer response to these drugs.
What happened to transgenic mice with a mutated version of the gene DISC1?
They developed enlarged lateral ventricles.
What is the significance of enlarged ventricles of schizophrenics?
Since the overall size of the brain does not increase the enlarged ventricles must come at the expense of brain tissue.
Among twins who are discordant for schizophrenia, the twin that is ill tends to have two brain structures smaller than the healthy one. what are they?
1) Hippocampus
2) Amygdala
How does the size of the ventricles and the size of hippocampus and amygdala correlated in schizophrenia?
The hippocampus and amygdala help form the walls of the lateral ventricles. Atrophy of the hippocampus and amygdala would cause enlargement of lateral ventricles and smaller hippocampus and amygdala structures. Which is what you see in schizophrenics.
Besides the hipocampus, amygdala and ventricles what other brain structures seems to be abnormal?
parahipocampal regions/cortex , entorhinal cortex, and cingulate cortex
When comparing the structure of the hippocampus of a schizophrenic to a person of the same age without the illness what were the differences discovered?
The Pyramidal cells of schizophrenic were disorganized, possibly resulting from abnormal synaptic arrangements of both the inputs and outputs of these cells. The most impaired individuals exhibited greatest disorganization.
The cellular disorganization of schizophrenia probably arises when?
during early cell development but because new neurons are made throughout life, especially in the hippocampus, abnormal neurogenesis or disordered integration of newly born cells could contribute to development of schizophrenia.
How do schizophrenics and controls differ structurally in the corpus callosum?
Schizophrenics tend to have a more accelerated loss of gray matter at adolescence than controls
What has test sensitive to frontal cortical lesions told us about schizophrenics?
Schizophrenics tend to be impaired on neuropsychological test that are sensitive to frontal cortical lesions. Raising the possibility that the frontal cortex was impaired in schizophrenics.
PET scans indicate what about schizophrenic patient’s frontal lobes?
That there is is relatively less metabolic activity in the frontal lobes compared to the posterior lobes. While in control subjects there is more-equal activation of frontal and posterior cortex.
In schizophrenic discordant twins frontal blood flow is reduced in which twin?
Only in the one with schizophrenia
Neurons in the frontal cortex of schizophrenic patients compared to controls?
the neurons in schizophrenic patients have dendrites with a reduced density of synaptic spines compared with control subjects., which may contribute to less active frontal cortex.
hypofrontality hypothesis for schizophrenia
Suggest that schizophrenia may be caused by the underactivation of the frontal lobes.
Cortical abnormalities in schizophrenics include what?
thicker corpus callosum and
altered function in this structure
lobotomy
surgical separation of a portion of the frontal lobes from the rest of the brain, as a treatment for schizophrenia.
Did lobotomies cure schizophrenia?
No, they may have made the patients easier to handle but they were rarely able to leave the mental institution.
How many lobotomies were performed in the United States?
~40,000 people. Used for almost all mental disorders not just Schizophrenia
What replaced lobotomies in 1954 as treatment for schizophrenia?
Chlorpromazine (trade name Thorazine)
Did Chlorprozamine actually work?
yes and in fact the symptoms that responded to chlorprozamine were exactly those that kept people in the mental institution.
Chlorproamazine could powerfully reduce what symptoms of schizophrenia?
Positive symptoms of schizophrenia, including: auditory hallucinations delusions disordered thinking *ONLY POSITIVE SYMPTOMS
What is the dopamine hypothesis for schizophrenia?
People with schizophrenia suffer from an excess or either dopmaine release or dopamine receptors.
Neuroleptics
antipsychotic drugs
chlorpromazine is an example of a neuroleptic
Chlorprozamine and later antipsychotic drugs that came along were found to share what specific action?
They block post synaptic dopamine receptors, particularly dopamine D2 receptors. Which lead to dopamine hypothesis.
How did drug abuse of amphetamines support the dopamine hypothesis?
people who took extremly large amount of amphetamine (as much as 3000 mg a day instead of 5 mg used to combat sleepiness) developed symptoms of schizophrenia. It turns out amphetamines promote the release of dopamine and prolongs the action of the released transmitter by blocking reuptake.
amphetamine psychosis
When individuals take such large dosages of amphetamine they develop symptoms of schizophrenia.
Can amphetamine psychosis be reversed?
yes; chlorpromazine treatment rapidly reverses amphetamine psychosis.
Drugs like LSP and mescaline produce some perceptual, cognitive and emotional changes but what is the difference between these hallucinations and schizophrenic hallucinations.
Drugs like LSP and mescaline produce perceptual hallucinations while schizophrenic hallucinations are auditory.
All typical neuroleptics are what?
D2 blockers; D2 receptor antagonist
How can the clinically effective dose of a typical neuroleptic be predicted?
By its affinity for D2 receptors, as the dopamine hypothesis would predict.
Which typical neuroleptic has a greater affinity for D2 receptors chlorpromazine or haloperidol?
Haloperidol, which quickly became the new widely used drug.
How can the treatment of parkinson induce schizophrenia-like symptoms
Those treated with L-dopa (metabolic precursor of dopamine) may induce schizophrenic-like symptoms, presumably by boosting the synaptic availability of dopamine.
What are the problems with the dopamine model?
there is no correspondence between the speed with which drugs block dopamine receptors (quite rapidly-within hours) and how long it takes symptoms to diminish (usually on the order of weeks). Thus the relation is more complex than just hyperactive dopamine synapses.
Some schizophrenics do not respond at all to dopamine antagonist.
dyskinesia
a symptom of typical neuroleptics
maladaptive motor symptoms; distortion in voluntary movement
when does dyskinesia occur
If dosage is to high when reduced they go away
Prolonged drug treatment, sometimes after months and sometimes years can cause drug induced motor changes. At this point they are effectively permanent.
tardive dyskinesia
characterized by repetitive, involuntary movements, especially involving the face, mouth, lips and tongue.
What are common uncontrollable movements involved in tardive dyskinesia?
incessant rolling movements of the tongue
sucking or smacking of the lips
twisting
sudden jerking movements of arms and legs
When does tardive dyskinesia occur?
frequently takes a long time to develop and tends to be irreversible.
Difference between D1 and D2 receptor binding of patients with tardive dyskinesia and those without symptom?
There is no difference.
What does prolonged blockage if dopamine receptors using antipsycotics tend to do to the number of dopamine receptors?
seems to increase the number of dopamine receptors and lead to receptor supersensitivty.
What type of drug treatment tends to have fewer dyskinesia side effects than typical neuroleptics?
atypical neuroleptics but are more likely to cause weight gain.
Why do atypical neuroleptics tend to have the motor side effects of typical neuroleptics?
atypical neuroleptics generally don’t have high affinity for dopamine receptors like typical neuroleptics but instead have a high affinity for other types of receptors.
Clozapine
an atypical neuroletic that selectively block serotonin receptors (especially 5HT2A receptors) as well as other receptor types.
Are atypical neuroleptics just as effective as typical neuroleptics?
Yes
clozapine increases _____ in the ______
dopamine; frontal cortex
How do atypical neuroleptics not support the dopamine hypothesis?
Atypical neuroleptics like clozaprine actually release dopamine and infact supplementing neuroleptics with L-dopa (increasing dopaminergic activity) actually helps reduce symptoms of schizophhrenia.
Are atypical antipsychotics better treatment fro schizophrenia than typical antipsychotics?
No they were found to be equally as effective. Although atypical neuroleptics are less likely to cause side effects in motor control but more likely to cause weight gain.
The Glutamate Hypothesis of schizophrenia
schizophrenia results from underactivity of glutamate receptors.
psychotomimetic
A drug that induces a state resembling schizophrenia
what is Phencyclidine (PCP)
is a potent psychotomimetic; produces phenomena strongly resembling both the positive and negative symptoms of schizophrenia.
Users of PCP usually experience what?
auditory hallucinations
strange depersonalization
disorientation
May become violent as a consequence of their drug-induced delusions.
PCP acts as a ______ receptor _____.
NMDA receptor antagonist
What happened when moneys were treated with PCP for 2 weeks?
produced schizophrenic-like syndrome, including poor performance o a test sensitive to prefrontal damage.
PCP as a NMDA receptor antagonist
PCP blocks the NMDA receptor’s central calcium channel, thereby preventing the endogenous ligand-glutamate- from having its usual effects.
Ketamine
Have similar affects as PCP and is another NMDA antagonist.
If glutamate hypothesis is true than compound that increase glutamatergic activity would be effective antischizophrenic drugs?
No these NMDA receptor agonist tend to produce seizures, so it is not an option.
symptoms of amphetamine psychosis?
These symptoms include: delusions, auditory hallucinations, paranoia, suspicious and bizarre motor behavior.
what are the affects of amphetamine on dopamine?
Amphetamine promotes the release of dopamine and prolongs the action of the released transmitter by blocking reuptake.
chloropromazine is a treatment for what?
amphetamine psychosis
when can super sensitivity psychosis emerge?
can emerge when drug doses are lowered; this reflects upregulation of receptors during treatment.
Clozapine does what to dopamine release?
Increases dopamine release in frontal cortex hardly what would be expected if the problem of schizophrenia was an over stimulation of dopamine receptors since Clozapine is an atypical neuropletic.
The glutamate hypothesis has been expanded to suggest that underactivation of ALL glutamate receptors, not just the NMDA subtype, contributes to schizophrenia. How may this help explain the effectiveness of atypical neuroleptics?
atypical neuroleptics act on 5HT2A serotonin receptors, because some metabotropic glutamate receptors form complexes with 5HT2A receptors. A typical neuroleptics that block 5HT2A receptors seem to make nearby mGluR’s more effective. So perhaps they reduce schizophrenia symptoms indirectly by boosting mGluR responsiveness. If so, then direct stimulation of the proper class of mGluR’s (there are atleast 8 subtypes) might provide a third generation of antipsychotics.
PCP act as a _____ and prevents _____ from acting normally?
acts as a NMDA receptor antagonist and prevents glutamate from acting normally.
What produces similar effects as PCP?
ketamine
An integrated model suggest that schizophrenia will develop if a compromised brain is exposed to _______
environmental stressors.
What environmental stress during pregnancy can cause an increase risk of schizophrenia?
If the mother has an infection while carrying the child, especially influenza. A baby that contracts influenza in the first trimester is 7 times more likely to develop schizophrenia.
Does a baby that contracts influenza have a greater risk for schizophrenia?
Yes a baby that contracts influenza in the first trimester is 7 times more likely to develop schizophrenia.
Does the season in which a baby is born correlate to increases of schizophrenia?
yes; People born in the late winter and early spring are more likely to develop schizophrenia probably due to mothers getting sick previous winter at some fetal stage that was particularly vulnerable.
Does blood type between mother and baby affect changes of schizophrenia?
yes; Babies who have mothers with incompatible blood types have a higher risk for schizophrenia?
Does the development of diabetes in a pregnant woman affect chances of baby developing schizophrenia?
Yes; if the mother develops diabetes during pregnancy the baby is at higher risk for schizophrenia.
Is birth weight of a baby correlated to schizophrenia?
Yes babies with low birth weights have higher chances of developing schizophrenia
Do birth complications that deprive a baby of oxygen increase probability of schizophrenia?
Yes, higher probability of development.
What age is the prevalence of schizophrenia?
age groups between 18-25
Is there evidence suggesting that living in a city or the country affect risks of developing schizophrenia?
yes; People born and raised in a medium-city are about 1.5 times as likely to develop schizophrenia than people living in the country. People in a big city are even more susceptible
Does the length of time in the city affect changes of developing schizophrenia?
Yes; the longer in the city the higher the risk of development.
Does moving out the city affect risks of developing schizophrenia?
yes; those that move out of the city have a reduced risk of development.
What are specific features (main features) that increases susceptibility of schizophrenia at the different life stages besides genetics.
before birth- infection
at delivery- delivery complications (reduced O2)
adolescence- social stress
adulthood- social stress
Depression is most common in people over the age of ____
40
Is depression more common in men or women?
women
Depression is characterized as what?
an unhappy mood; loss of energy, interest and appetite; difficulty in concentration; restless agitation. Pessimism seems to seek into every act.
what is unipolar depression?
depression that alternates with normal emotional states.
Does unipolar depression occur due to stress?
No it can occur with no readily apparent stress.
Without treatment how long can depression last?
last for several months
Depressive illness is estimated to afflict how much of the population?
13-20% at any one time
Is inheritance a factor of depression?
yes; for monozygotic twins is ~ 60% and for dizygotic twins its ~ 20%. The concordance rate is ~ the same rather the twins are reared together or apart.
Adoption shows that there is a higher rate in depression of (biological or foster parent)?
Higher rate in biological parents
If it is genetic than what genes cause it?
No specific genes but an array of genes that make one more susceptible to depression
about _____% of all suicide victims are profoundly depressed
80%
What suggesting that suicides appear to be impulsive acts?
Of the 500 people who were prevented from jumping off the Golden Gate bridge only 6% later went on to commit suicide. Also in great Britain when coal gas containing deadly monoxide was replaced with natural gas for heating and cooking suicide went down and has stayed down for last 40+ years
A more common name for manic-depressive disorder
bipolar disorder
What characterizes bipolar disorder?
repeated fluctuation between depressive periods and episodes of euphoric, sometimes grandiose, positive mood (or mania).
In depressed individuals there is an increase in blood flow to the ______ and _____
an increase in blood to the prefrontal cortex and amygdala
In depressed individuals there is a decrease in blood flow to the _____, _____, and ____, systems implicated in _____
a decrease in blood flow to the parietal cortex, posterior temporal cortex and anterior cingulate, systems implicated in attention
Fear is mediated by the ____
amygdala
after depression is alleviated over time blood flow to the ____ persist
amygdala, which mediates fear.
Descendants of people with severe depression have thinner cortex across large swaths of the _____ hemisphere.
Right
Many report reduced volumes in the _____ in people with depression and reduced activation in this area in depressed people during ______ tasks
hippocampal; during memory task.
what is Electroconvulsive shock therapy (ECT)
the intentional induction of a large-scale seizure by passing an electric current through the brain.
ECT was first used to help those suffering from _____ but clinical observations soon revealed it could rapidly reverse severe _____.
schizophrenia; depression.
ECT is now used only for _____ depression since medication treatment is now a thing.
severe, drug-resistant depression.
Transcranial magnetic stimulation (TMS)
alters coritcal electrical activity, used for treating depression
What is the most common treatment for depression today?
the use of drugs that affect monoamine transmitters.
what do Monoamine oxidase (MAO) inhibitors do?
they are a treatment for depression; they inhibits the enzyme that inactivates the monoamines.: norepinephrine, dopamine and serotonin
What are the three main monoamines?
Norepinephrine
dopamine
Serotonin
MAO inhibitors ______ the raise the level of monoamines present in synapses suggests that depressed people do not ______ at those synapses.
raise; do not get enough stimulation
reserpine
reduces norepinephrine and serotonin (both monoamines) release in the brain, can cause profound depression.
tricyclics
second generation of antidepressants, conform to the monamine hypothesis because they inhibit the reuptake of monoamines, boosting their synaptic.
Selective serotonin reuptake inhibitors (SSRIs)
a major class of modern antidepressants; such as prozac. These drugs are more effective than MAO inhibitors and tricylics and have fewer side effects.
Prozac
Selective serotonin reuptake inhibitors (SSRIs)
In rats, SSRIs ______ neurogenesis in the _____
increase; hippocampus
SRRIs ____ production of brain steroids
Increase
allopregnanolone
Is a brain steroid
What may be a role of brain steroids?
It may contribute to the effectiveness of SSRIs by stimulating GABA receptors and reducing anxiety.
zoloft
an SSRI
Paxil
SSRI
Nardil
MAO inhibitor
Marplan
MAO inhibitor
Parnate
MAO inhibitor
SSRIs increase the risk of what is both adults and adolescents?
increase risk of suicide
If serotonin levels get too high it can trigger what?
Serotonin syndrome
Problems with theory of serotonin reduction as a cause of depression
- Long lag time between treatment and reduction of symptoms.
- Not everyone is helped, and there is also a large placebo effect.
How many people in a drug trial for the depression treatment SSRIs feel better on a placebo?
1/3rd
what percent of depressed patients respond better to SSRIs than placebo
13% and these are the most sever cases
% of patients on SSRI completely “cured”
50%
% patients who have no improvements when on SSRIs?
20% so no improvement at all
What is the problem with SSRIs and over-the-counter drugs?
A variety of over the counter drugs can synergize with the drugs to push synaptic serotonin levels too high, triggering serotonin syndrome
What are symptoms associated with serotonin syndrome?
confusion muscle spasms, and fever.
How many cases/deaths due to serotonin syndrome are reported each year?
Thousands of cases are reported, causing over 100 deaths.
The glutamate receptor ketamine may be related to depression how?
It may be a potent antidepressant
Vagal nerve stimulation
a treatment for depression; electrodes are surgically wrapped around the vagus nerve in the neck, and a pacemaker provides mild electrical stimulation at intervals
Dexamethasone
a synthetic glucocorticoid, can suppress cortisol release in normal people but not in depressed patients.
Phototherapy
administered in the morning can suppress melatonin, a hormone that is normally released from the pineal gland at night
Melatonin
may aid SAD if given in the afternoon.
In Cyclothymia
milder form of bipolar disorder—patients cycle between dysthymia (mild depression) and hypomania (increased energy).
PTSD victims have decreased volume in the
right hippocampus
