Let 14/15

Question 1

what is schizophrenia?

Answer 1

• -classified as psychotic disorder
• -means a loss of contact with reality
• -8 separate different disorders we classify as schizophrenia

Question 2

how many people does schizophrenia affect?

Answer 2

• -Schizophrenia affects approximately 1/100 people in North America.
• -The annual cost of schizophrenia in the US is estimated at around $60 billion, due largely to the cost of treatment and lost wages

Question 3

Who was Emil Kraeplin?

Answer 3

• -the first to thoroughly define the symptoms of schizophrenia, combining several elements of insanity into one disorder
• -Catatonia (means your frozen), hebephrenia (silly and immature emotionality), and paranoia had previously been as separate disorders.
• -called schizophrenia dementia praecox – “premature dementia” because the disorder usually appears in late adolescence and believed these symptoms were a result of premature aging of the brain

Question 4

Who was Eugen Bleuler?

Answer 4

• -introduced the term schizophrenia, replacing Kraeplin’s “dementia praecox”.
• -it shows that Bleuler believed that the core problem was not premature aging of the brain.
• -The word schizophrenia means “split mind”, and this comes from Bleuler’s belief in the “breaking of associative threads”(split from reality) – the various elements of the individual’s mind become disconnected from each other. Thoughts no longer have any logical connection to each other, or to reality in general.
• -the concept of “split mind” has lead to the popular but incorrect use of schizophrenia to refer to split/multiple personalities

Question 5

What are the positive symptoms of schizophrenia?

Answer 5

• -Delusions of grandeur (believing you are famous or important), delusions of persecution, erotomanic delusions (believes that another person, usually a celebrity, is in love with him or her)
• -Delusions can be classified as bizarre if they are clearly implausible (Belief that an outside force has removed the individual’s internal organs and replaced them with those from someone else)
• -Delusions can instead be non-bizarre, if they are somewhat plausible (Believing that the government is listening to the individual’s phone calls)
• -Delusions expressing a loss of control over mind and body are common (Belief that outside forces are inserting thoughts into one’s mind, or that one’s body is being manipulated by some outside force)
• -Hallucinations: the experience of sensory events without any input from the surrounding environment.
• -Hallucinations can involve any of the senses, but auditory hallucinations such as voices are the most common in schizophrenia (most are a running commentary but some are more sinister)

Question 6

What is a delusion a lot of people with schizophrenia have?

Answer 6

–Lots of people with schizophrenia think they have these transponders implanted in their brains by aliens or army
If you google transponder implants, there are many websites that support this belief

Question 7

What can produce hallucinations?

Answer 7

If people are completely deprived of sensory input, it produces hallucinations

Question 8

What does pathognomonic mean?

Answer 8

• -pathognomonic: symptom is unique to a given disorder

- -Paranoia, psychosis, hallucinations are not pathognomonic to schizophrenia

Question 9

What are the negative symptoms of schizophrenia?

Answer 9

• -Apathy: the inability to “get started”, to perform basic day-to-day functions
• -Autism: refers to the tendency to keep to oneself and lose interest in other people or the surroundings.
• -Ambivalence: emotional and social withdrawal.
• -Anhedonia – “without pleasure (G.)”: indifference to activities that are typically considered to be pleasurable.
• -Affective flattening: the absence of visible emotions, facial expressions, and emotional inflections in speech (25% of people with schizophrenia)

Question 10

What are the cognitive symptoms of schizophrenia?

Answer 10

• -Disorganized speech: people with schizophrenia have a confusing way of talking (They often jump about randomly from topic to topic, or go off on illogical tangents)
• -Inappropriate affect: occasionally, people with schizophrenia display emotions that are inappropriate for the current situation.
• -Disorganized behaviour: people with schizophrenia can show motor symptoms ranging from wild agitation to catatonic immobility (seem frozen in place, but may display waxy flexibility)

Question 11

What is the DSM-5 diagnostic criteria for schizophrenia?

Answer 11

1) delusions
2) hallucinations
3) disorganized speech
4) grossly disorganized or catatonic behaviour
5) negative symptoms
- -individuals must have at least one of the first 3
- -long-lasting symptoms
- -not due to drugs or some other medical condition

Question 12

What is the development of schizophrenia?

Answer 12

• -schizophrenia is usually diagnosed in late adolescence or early adulthood
• —>It strikes right as people enter the world and begin to gain independence
• -In 85% of people, full-blown schizophrenia is preceded by a prodromal stage – a 1-2 year period where subdued symptoms begin to appear.
• —>Magical thinking (thinking they can do things they actually can’t) minor illusions (feeling of a presence when one is alone, etc.,), and ideas of reference (everything out there is a signal to you. It has personal meaning and has something dark associated) are common prodromal symptoms

Question 13

What is the prognosis of schizophrenia?

Answer 13

• -Complete remission is rare: most people (~78%) being treated for schizophrenia go through a pattern of relapse and recovery.
• -The prognosis for schizophrenia is poorer than for most other disorders, but recovery/remission is more likely given the following factors:
• —>Good social adjustment prior to onset of schizophrenia (high socioeconomic class).
• —>A low proportion of negative symptoms.
• —>A good social support system for patients
• -The symptoms of schizophrenia may decrease with age, or at least “level out

Question 14

What is the genetic etiology of schizophrenia?

Answer 14

• -Monozygotic (identical) twins share 100% of their genes.
• -Therefore, if schizophrenia was 100% caused by genetics, both twins would always have schizophrenia.
• -In reality, the risk is only 48%.

Question 15

What are the prenatal factors of schizophrenia?

Answer 15

–There is evidence that problems before and shortly after birth (the perinatal period) can increase the risk of developing schizophrenia
—->When mom is stressed while pregnant, the baby is stressed, and it puts the baby at a higher risk for schizophrenia (Stress kills of brain cells. the specific neurons that are affected by this are the ones in the hippocampus (the hippocampus is implicated in schizophrenia)
—->Fetal exposure to influenza and other virus-like diseases may subtly damage the fetal brain in a way that causes the symptoms of schizophrenia later in life.
Toxoplasmosis gondii (t.gondii): comes from cat litter so this is why pregnant women shouldn’t change cat litter
—->Famine – nutritionally deprived moms are stressed and the lack of nutrients along with the stress can affect the development of fetus/baby’s brain
—->Pregnancy and delivery complications are also correlated with the development of schizophrenia: ex prenatal hypoxia

Question 16

What is the stress etiology of schizophrenia?

Answer 16

• -Stress can act as an epigenetic factor to promote the incidence of schizophrenia to individuals who are at risk (the ones who have the genes for schizophrenia that puts them at risk for maybe developing it)
• —->Stress can unlock these genes through acetylation/methylation depending on where the genes are
• —>Numerous studies have shown that diagnoses of schizophrenia are often preceded by a stressful life event.
• —>Anecdotal evidence seems in favor of this as well. Schizophrenia often appears in the midst of the stressful transition to independent living that young adults undergo.

Question 17

How is the brain anatomy of patients with schizophrenia different?

Answer 17

–enlarged lateral ventricles
—->enhanced white matter and loss of grey matter
—->suggests that nearby parts of the brain either did not develop properly, or have atrophied (cell death).
–It is difficult to tell whether this observation causes schizophrenia, or if it’s simply a consequence of the disease.
—->Genetic studies suggest that enlarged ventricles are an inherited risk factor, present in both people with schizophrenia and their healthy siblings
–reduced dendritic spine density in the prefrontal cortex
–reductions in the size of the hippocampus
—->Hippocampus is most affected by stress because they have GR receptors that cortisol binds to
Hippocampus is also responsible for neurogenesis
—->reductions in hippocampal volume are due to degradation. Young patients who are just showing symptoms for the first time have normal sized hippocampi.
—->The degree of hippocampal degradation is correlated with illness severity – people with worse symptoms have smaller hippocampal volume
–Post-mortem samples show disorganized neurons in the hippocampus of schizophrenia brains

Question 18

What antipsychotic drug is used for schizophrenia and how was it an important breakthrough?

Answer 18

• -chlorpromazine (trade name: Thorazine) is the first discovered member of the phenothiazine family of first-generation antipsychotics.
• -Chlorpromazine was tried as an anesthetic and for various other purposes, but it produced amazing success when given to psychotic patients.
• -they reduce psychotic symptoms without producing too much general sedation.
• —>This breakthrough allowed patients to finally leave their institutions and resume normal life
• —>The deinstitutionalization movement was kick-started by the discovery of chlorpromazine.

Question 19

How do antipsychotic drugs work on schizophrenia?

Answer 19

–The dopaminergic neurons in the VTA of the midbrain project dopamine to various areas of the forebrain (the cell bodies are in the VTA and the axons are spread out to other areas to project dopamine) including the striatum. The ventral striatum is also known as the nucleus accumbens (NAc) which is involved in reward and the dorsal striatum is involved in movement
–seems that the striatum (part of basal ganglia) is the most important for schizophrenia.
–The dopamine binds to D2 receptors in these regions.
Chlorpromazine blocks these D2 receptors it matches the shape of dopamine but it sits and occupies the receptor so dopamine cannot bind to it (antagonist) so these antipsychotics are D2 receptor blockers/D2 antagonist
–The better its binding to the D2 receptor site, the more it’s able to reduce the psychosis

Question 20

What causes the positive symptoms of schizophrenia?

Answer 20

• -caused by excessive stimulation of dopamine D2 receptors in the striatum.
• -blocking dopamine D2 receptors in the striatum with drugs like chlorpromazine relieves the positive, psychotic symptoms of schizophrenia.
• -these first-generation antipsychotics only reduced the positive symptoms of schizophrenia but were not good at treating the negative and cognitive symptoms

Question 21

How does dopamine play a role in schizophrenia?

Answer 21

• -It turns out that stimulant drugs such as cocaine and amphetamine can, when taken in high doses, produce psychosis in drug users
• -So in general, drugs that decrease dopamine signaling reduce psychosis, drugs that increase dopamine signaling cause psychosis
• -It turns out that schizophrenia may also involve under-stimulation of dopamine D1 receptors in the prefrontal cortex.
• —>This condition is called hypofrontality, and it can explain why people with schizophrenia often struggle with planning, problem solving, and high-level reasoning.
• -The ideal drug would be able to block D2 receptors, but activate D1 receptors
• -We’re realizing that it might be a dysregulation of GABA and glutamate (they modulate activity of monoaminergic projections such as dopamine and serotonin) so they can’t control the output of the dopamine system

Question 22

How do PET scans work?

Answer 22

• -detects changes in blood flow by measuring changes in the uptake of compounds such as oxygen or glucose
• -Inject with a radioactive ligand
• -We can tag that radioactive ligand to specific proteins so we can have a radioactive ligand for the D2 receptor so it will bind to the D2 receptor and it will image that D2 receptor when we put the person through the scanner
• -We’re measuring changes in blood-glucose because when cells are active, it will take up glucose
• -Temporal resolution: we can quickly see which populations of cells are active
• -Poor spatial resolution: can’t tell exactly which population of cells are active

Question 23

What are the side effects of antipsychotics?

Answer 23

• -While the antipsychotics can often be very successful in relieving patients of the symptoms of schizophrenia, patient non-compliance is a huge concern.
• —>approximately 40-50% of patients on antipsychotic medication stop taking them within the first year.
• —>Reasons: Side effects (e.g., sedation, excess salivation, motor function), feeling of “being fine”
• —>Quitting these drugs can have disastrous effects. The full spectrum of schizophrenia symptoms can return after only a few days.
• —>A relapse into psychosis can quickly destroy years’ worth of therapy and attempts to build a stable life.
• —>Quitting these drugs can have disastrous effects. The full spectrum of schizophrenia symptoms can return after only a few days.
• -Ideally, patients should be supervised to ensure that they take their medications appropriately.
• —>even in institutional settings, “cheeking” pills is common
• —>Moreover, there are ethical concerns with forcing people to take medications (with the possible exception of violent criminals).