Define illusion

Severely distorted perceptions or misinterpretations of stimuli

Define delusion

Fixed, false beliefs that are not shared by others in an individual's culture

Define 'ideas of reference'

Beliefs that ordinary objects, such as license plates, contain
specific messages for the person
When the person is unable to question these beliefs, they are called
delusions of reference

Where, besides schizophrenia, might psychotic symptoms occur?

Mood disorders such as mania and in the most severe cases of depression

Describe schizoaffective disorder

When chronic schizophrenia-like symptoms predominate and are coupled
with mood disorders such as depression and mania
- Highly heterogenous grouping

Describe schizophreniform disorder

When schizophrenia-like symptoms are developed acutely, experienced
transiently, and a full recovery is made
- Classified as a "noneffective psychotic disorder

Describe delusion disorder

When individuals harbor chronic delusions without other symptoms of
schizophrenia such as hallucinations or cognitive symptoms

Outside of a disorder, psychotic symptoms may occurs as a result of:

1. Drugs of abuse
2. Toxins
3. Metabolic derangements

Delusions and hallucinations may also occur in....

Neurogenerative disorders such as Alzheimer's and Huntington's disease

What are the three major clusters that the symptoms of schizophrenia form?

1. Positive
2. Negative
3. Cognitive

List and describe positive symptoms associated with schizophrenia

Mental phenomena (psychotic symptoms) that are absent in healthy individuals
- Hallucinations: Most commonly auditory and perceived as sounds or voices
- Delusions: Most commonly bizarre or paranoid

List and describe negative symptoms associated with schizophrenia

Loss or significant impairment of normal psychological functions
- Amotivation
- Asociality
- Inattention to self-care
- Blunting of affect
- Impoverishment of the content of thought and speech

Define hypofrontality

The view that negative symptoms of schizophrenia involve impaired
functioning of the prefrontal cortex

List and describe cognitive symptoms associated with schizophrenia

Deficits in executive function
- Impairment in working memory
- The ability to hold information "on line" that can be
used to guide thought or behavior
- Deficits in episodic memory

Schizophrenia most often manifests during what time in life?

The late teens or early 20s, although earlier or later may occur

There is a period of ______ symptoms preceding the diagnosable onset
of schizophrenia
What do these symptoms consist of?

Prodomal
- Difficulty at school or work
- Becoming socially isolated
- Becoming increasingly eccentric
Diagnosis usually made with the appearance of psychotic symptoms

Antipsychotic drugs work to:

Treat acute episodes of psychosis and extend the period between relapses

The global mean of the prevalence of schizophrenia is

Somewhere between .5% and 1%

What is the approximate ratio of the gender disparity in schizophrenia?
Which gender tends to have earlier onset of the illness?

1.4 Male:1 Female
Males tend to have earlier onset of the illness

Schizophrenia exhibits a strong genetic basis, specifically a

Epigenetic basis (as reinforced by studies done on DZ twins)

Describe schizotypal personality disorder

Blood relative of schizophrenics who do no shave psychotic symptoms
but may exhibit some degree of social isolation, suspiciousness,
eccentric beliefs, or magical thinking

The two genes that have thus far been implicated in gene studies of
schizophrenia are:

1. DISC1
2. NRG1 and its receptor erbB-3

What are a couple functions implicated in schizophrenia-like
behaviors that NRG1 helps regulate?

#NAME?

Potential environmental risk factors for schizophrenia include:

- Urban brith
- Increasing paternal age
- Intrauterine exposure to viral infection (particularly the flu)
- Maternal starvation during pregnancy
-- Cortical and hippocampal development are in a "critical
period" during the 2nd trimester of a pregnancy, when neuronal
differentiation and migration occur

Describe some of the cognitive deficits associated with schizophrenia

Tasks that require symbolic or verbal representation
Difficulty integrating novel stimuli with older memories or concepts
Treating familiar associations as though they were unusual
Treating new situations as if they occurred in the recent past

The disorganization of speech and loosening of associations that
characterize schizophrenia may stem from:

An inability to keep recent thoughts or words in mind

Describe working memory

The ability to represent information, manipulate it, and order it
thus permitting a person to exert "cognitive control" over
thoughts, emotions, and behavior

What specific area of the brain has been implicated through human and
primate studies in the area of working memory?

The dorsolateral prefrontal cortex

Describe the Wisconsin Card Sorting Test (WCST) and the difference in
performance between neurotypical and schizophrenic test subjects

The WCST has subjects sort cards based on color, shape or number. The
subject must learn the correct sorting criteria based on responses
given by the experimenter.
At some point, the experimenter changes the criteria and subjects
must notice and adapt to this.
Due to their inability to suppress automatic responses to familiar
stimuli, schizophrenics do not perform as well as neurotypical
subjects once the criteria has been changed

Describe the Stroop test and why schizophrenics do not perform well
in it

The Stroop test presents cards with the name of a color written in
ink of a different color. Subjects are supposed to provide the name of
the color of the ink, rather than the name of the color that is written.

What other neuropsychological test was discussed that shows decreased
prefrontal cortex abilities in schizophrenics?

The delayed match-to-sample test
The smooth pursuit eye-movement tracking test (with the pendulum)

What receptor has been implicated in working memory and exhibits a
U-shaped dose response curve?

The D1 dopamine receptor
- depends on the cAMP pathway, is Gs linked
Explains why antipsychotic drugs (may of which have D1 dopamine
receptor antagonist properties) may worsen working memory performance
in schizophrenics

List the neurantomic differences between neurotypical and
schizophrenic subjects

- Thinning of gray matter in the prefrontal (especially the
dorsolateral prefrontal cortex - responsible for working memory) and
temporal regions of the cerebral cortex
- Compensatory enlargement of the third and lateral ventricles
-- The above neuroanatomical differences seem to be more pronounced
in males than in females
- Abnormal functioning of the anterior regions of the hippocampus
(esp. the CA1 region)

A loss of what seems to be responsible for the loss of volume in the
frontal and temporal cortical regions?

Neuropil, a substance composed of dendritic and axonal processes
- Accompanied by loss of dendritic spines and very likely loss of synapses

A lack of loss of what indicates that schizophrenia is not a
neurodegenerative disorder?

Cell loss, gliosis, or inflammation
Schizophrenia is then most likely to be the result of abnormal brain development

Describe how the typical age of onset of schizophrenia supports the
neurodevelopmental hypothesis

It is during this time that the brain undergoes its last significant
period or maturation
- Completion of the myelination of the axon fibers in frontal
regions of cerebral cortex
- Significant synaptic pruning (The maintenance of synaptic
connections used effectively during development and the discarding of
those that have not)
-- May be a particularly robust process in the prefrontal cortex
Coincides with major changes in dopamingeric neurotransmission in
this brain area during late adolescence

Schizophrenia may result from an aberration in glutamatergic function

#NAME?

Phencyclidine (PCP) - Angel Dust
&
Ketamine - special K

Drugs that block NMDA glutamate receptors (functions as open channel blockers)
- Produce a sense of depersonalization and dissociation of
subjective experience from sensory stimuli (nociceptive signals might
not be experienced as aversive)
- Can produce visual and auditory hallucinations
- PCP can cause profound retrograde amnesia

The receptor thought to implicated in the major actions of PCP

The sigma receptor
- Originally thought to be an opioid receptor, but is not blocked by
naloxone and binds diverse drugs unrelated to opioids

Describe neuroleptic medications

The first generation of antipsychotics which cause remission of
hallucinations and delusions, but cause motor side effects such as
tremor and rigidity
i.e. they block dopamine receptors, leading to a compensatory
increase in dopamine release in the striatum and thereby to an
increase in dopamine breakdown products such as HVA
- Cause an increase in the dopamine metabolite homovanillic acid
(HVA) in the striatum
Examples: Chlorpromazine and reserpine

How does chlorpromazine work and what is it classified as?

Acts as a D2 antagonists
Classified as a neuroleptic

How does reserpine work and how is it classified?

Targets the vesicular monoamine transporter, reduces levels of
dopamine, norepinephrine, and seratonin
Classified as a neuroleptic

This antipsychotic has a high affinity for D2 and D3, but not D1 receptors

Haloperidol

The D1 binding site consists of what receptors?

D1 & D5

The D2 binding site consists of what receptors?

D2, D3, and D4

What explains the slow efficacy of antipsychotics?

Slowly accumulating adaptations of cells, synapses, and neural
circuits to sustained blockade of D2 receptors

Explain side effects of antipsychotics related to the D2 receptor antagonism

#NAME?

What are the four major categories that extrapyramidal side effects
can be divided into? Describe each of them.

1. Symptoms that resemble Parkinson disease
- Rigidity, difficulty in initiating movements, mask-like facial
expressions, and a resting tremor
2. Acute dystonia
- Sudden and spastic contraction of muscles - often of the face and neck
3. Akathisia
- Subjective sense of anxiety and intense restlessness (commonly
mistaken for psychotic agitation)
4. Tardive dyskinesia
- Late onset involuntary abnormal choreiform movements

What test would be used to judge affinity and receptor occupancy of
antipsychotics in humans?

A PET scan

Psychotic symptoms are generally congruent with a person's elevated
or depressed mood when they occur in _____

Mood disorders
- Elevated: Prophet/superhero
- Depressed: Hear thoughts telling them they are worthless

Of the three categories of symptoms schizophrenia produces, which is
the most resistant to medication?

The cognitive symptoms - tend to be unremitting

The lifetime prevalence of psychosis of all cause may be between

3% and 4% of the population

Although schizophrenia is well documented as having a genetic basis,
it has not been shown to exhibit

Typical Mendelian patterns of dominant or recessive transmission

Even in monozygotic twins, what percentage of the pairs are
discordant (i.e. one twin develops schizophrenia and the other does
not) ?

50%
- This underscores the important role of nongenetic factors

The increase in dizygotic twin concordance over sibling concordance
(both of which share approximately 50% of their DNA) can be explained through:

Epigenetic factors
- Epigenetic modification of the genome by such processes as
methylation of DNA or covalent modification of the histone proteins
that are the major constituent of chromatin
-- Changes in gene expression that could strongly influence brain development

Psychostimulants such as amphetamine and cocaine, and L-dopa cause:

Paranoid delusions, ideas of reference, and auditory hallucinations
- But only after prolonged use at high doses
- Supposedly by increasing synaptic levels of dopamine

The risk an antipsychotic seems to display in producing
extrapyramidal side effects and elevated prolactin levels seems to be
related to

The affinity of a drug for the D2 dopamine receptor and the dose used

A drug that can be given with an antipsychotic to help ameliorate
extrapyrdamidal side effects are drugs that exhibit these properties

anticholinergic (antimuscarinic) properties
- This does not help hyperprolactinemia

List and describe the cause of the off-target side effects associated
with antipsychotic medications

Sedation
- Results form the blocking H1 histamine receptors, muscarinic
cholinergic receptors, and possibly alpha1-adrenergic receptors in the CNS
Hypotension
- Antagonism of alpha1-adrenergic receptors in the CNS
Dry mouth, blurred vision, urinary retention, and constipation
- Antagonism of muscarinic cholinergic receptors
Delirium
- Blockade of muscarinic cholinergic receptors in the CNS

Describe clozapine

A second generation (atypical) antipsychotic medication
- Has far fewer extrapyramidal side effects when compared to other
antipsychotics and can significantly improve negative symptoms
- Can result (in about 1% of patients) in agranulocytosis (a
decrease in white blood cells)
- May also produce sedation, weight gain, drooling, and a decrease
in seizure threshold

Where does Clozapine have a high affinity for? Where are these
receptors found?

D3 and D4 receptors
- Low levels in the dorsal striatum
- Higher levels in the ventral striatum and in the prefrontal cortex
5HT-2a receptors - High affinity antagonist
5HT-2c, 5HT-3, and 5HT-6

A selective antagonist for this receptor failed to exhibit
antipsychotic properties

D4

This ratio became a design principle for many second-generation antipsychotics

A high 5HT2a : D2 receptor affinity

Describe Ariziprazole

A second generation antipsychotic with a high affinity antagonist at
5HT2a receptors and a partial agonist at D2 receptors, serving as an
agonist in dopamine-poor environments and an antagonist in
dopamine-rich environments
- Low extrapyramidal liability and does not elevate prolactin

A higher D2 receptor affinity typically means an elevated risk for what?

Extrapyramidal side effects

While they have a decreased risk of extrapyramidal side effects,
second generation antipsychotics have their own plethora of side
effects. List them.
What could these side effects be caused by?

- Weight gain
- Elevate serum glucose and cholesterol
- Drug-induced metabolic syndrome could produce a high risk of
diabetes and cardiovascular disease
May be caused by a blockade of 5HT-2c receptors in
melanocortin-expressing neurons of the hypothalamus

The hypothesis surrounding glutamatergic functioning and NMDA
receptor functioning has led to the use of this to treat schizophrenia

Glycine
- Promotes NMDA receptor function by bindng to a positive allosteric
regulatory site on the receptor complex
Specifically, D-cycloserine, a partial agonist at this glycine site

These, who's binding sites propose a whole new basis of antipsychotic
activity, have also been considered because of their influence in
glutamatergic activity

mGluR2 & mGluR3
- Gi-linked receptors
- Activation of these receptors decreases glutamate release
- Devoid of any binding activity at dopamine or other monoamine receptors

Neuroleptics target these receptors in (predominantly) these pathways:

D1 & D2
Nigrostriatal
Mesolimbic

Atypical antipsychotics target these receptors in (predominantly)
these pathways:

D3 & D4
Mesolimbic
Mesocortical

Describe the hippocampal dysregulation of dopamine system functioning
in a schizophrenic individual

Under normal conditions, the ventral palladium produces some tonic
inhibition of VTA DA neurons
- When something rewarding happens only the neurons that are not
being inhibited can be excited
- A theory for schizophrenics, is that none (or significantly less)
of their DA neurons in the VTA are being inhibited