Week 11

Question 1

Schizophrenia

Answer 1

• is a severe mental disorder which affects around 1% of the population. It is characterized by disordered thoughts, delusions, hallucinations, and often bizarre behaviour
• The symptoms of schizophrenia usually appear gradually over time, beginning in late adolescence or early adulthood. The main symptoms can be classed as as being positive, negative or cognitive

Question 2

Positive symptoms of schizophrenia

Answer 2

are symptoms in schizophrenia that are evident by their presence including delusions, hallucinations or thought disorders.

Question 3

Delusions - schizophrenia

Answer 3

• are beliefs that are contrary to fact and that are not common in the groups, communities, or family to which the person belongs.
• Individuals can experience delusions of grandeur which are false beliefs in one’s power and importance (e.g., the conviction of having supernatural powers), as well as delusions of control where the person might believe that they are being controlled by others (through something such as an implant in their brain)

Question 4

Hallucinations - schizophrenia

Answer 4

• are perceptions of stimuli that are not actually present (e.g., hearing sounds that are not present).
• Auditory hallucinations are most common occurring in about 70% of individuals with schizophrenia.

Question 5

A thought disorder - schizophrenia

Answer 5

• refers to having irrational, disorganized thinking.
• This symptom results in individuals having difficulty arranging their thoughts logically and distinguishing plausible from improbable conclusion

Question 6

Negative symptoms - schizophrenia

Answer 6

are symptoms in schizophrenia characterized by the absence of behaviours that are normally present such as reduced emotional response, lack of speech, lack of initiative and persistence, anhedonia and social withdrawal.

Question 7

Cognitive symptoms - schizophrenia

Answer 7

• The cognitive symptoms of schizophrenia may be produced by abnormalities in the brain regions that overlap with those involved in negative symptoms
• For example, the symptoms can involve difficulty sustaining attention, low psychomotor speeds, deficits in learning and memory, poor abstract thinking, and poor problem types

Question 8

Schizophrenia and genetic factors

Answer 8

• Genetic studies generally suggest that heritability
plays a role in the development of schizophrenia
• There is no single “schizophrenia” gene, rather
research suggests that many genes appear to
increase the likelihood of having schizophrenia
• ‘Schizophrenia genes’ might impart a susceptibility
to develop schizophrenia, but the disease is
triggered by other factors

Question 9

Schizophrenia and genetic factors - mutations

Answer 9

• A rare mutation of the gene DISC1 (disrupted in schizophrenia
1) appears to be associated with schizophrenia.
• Mutation presence increases the likelihood of schizophrenia by a factor of 50 + increases chance of other conditions such as major depressive disorder.
• DISC1 is involved in regulation of embryonic and adult neurogenesis, neuronal migration during embryonic development, function of postsynaptic density in excitatory neurons and the function of mitochondria.

Question 10

Schizophrenia and genetic factors - twin and adoption studies

Answer 10

• Twin and adoption studies suggest that schizophrenia is a heritable trait
• Past research assumed that discordance for schizophrenia in monozygotic (identical) twins must
have been due to environmental exposure differences after birth.
• However, the prenatal environment of monozygotic twins is not always identical (i.e. they can have the same or different placenta)

Question 11

Schizophrenia and genetic factors - twin studies with separate placenta

Answer 11

• The placenta transports nutrients, removes waste products and provides a barrier to toxins that could affect fetal development
• Davis et al. (1995) found the concordance rate for schizophrenia among twins who shared a placenta
was 60%, but only 10.7% for twins who did not share a placenta

Question 12

Schizophrenia and genetic factors - paternal age

Answer 12

• The effect of paternal age further suggests that genetic mutations impact schizophrenia incidence
• Children of older fathers are more likely to develop
schizophrenia
• Increased likelihood of mutations in chromosomes of cells that produce sperms

Question 13

Schizophrenia and genetic factors - epigenetics

Answer 13

• Epigenetic factors may predispose people to
schizophrenia
• Epigenetic mechanisms control the expression of genes and are influenced by an individual’s experiences
• Many epigenetic changes are initiated by environmental events such as exposure to toxins, and some epigenetic changes can be transferred to offspring

Question 14

Epidemiology

Answer 14

is the study of the distribution and causes of

diseases in populations

Question 15

Epidemiology and schizophrenia

Answer 15

Evidence from epidemiological studies suggests that
schizophrenia incidence is associated with:
• Season of birth
• Viral epidemics
• Vitamin D deficiency
• Population Density
• Prenatal Malnutrition
• Substance Abuse
• Complications of Birth and Pregnancy

Question 16

Seasonality effect

Answer 16

People born during the late winter and early spring are more likely to develop schizophrenia

Question 17

Viral epidemics and the seasonality effect

Answer 17

• Why would the seasonality effect occur?
• Perhaps pregnant women are more likely to contract a viral illness during a critical phase of development if they are pregnant during autumn or winter
• Results in brain development being impacted by a toxin produced by the virus (or antibodies fighting the virus) which crosses the placenta barrier.

Question 18

Vitamin D deficiency and the seasonality effect

Answer 18

• Cold weather could contribute to the seasonality effect via viral infections, but another factor could be Vitamin D, which plays a role in brain development
• Taking a Vitamin D supplement during the first year of a child’s life was associated with reduced incidence of
schizophrenia among boys

Question 19

Population density and the seasonality effect

Answer 19

• The seasonality effect is more prevalent in cities compared to rural areas (3 times higher likelihood of developing schizophrenia)
• Could be because viruses are more readily transmitted in high density populations (prenatal influences)
• Furthermore, Pederson and Mortensen (2001) found that up to the age of 15 years, the longer the person lives in a city, the more likely they are to develop schizophrenia (postnatal influences)

Question 20

Prenatal stress and schizophrenia

Answer 20

• Malnutrition and Stress seem to play a role
• Underweight women are more likely to give birth to babies who later develop schizophrenia
• Prenatal stressors such as exposure to a terrorist attack are associated with increased incidence of schizophrenia in offspring
• Complications during pregnancy and birth can contribute to Schizophrenia

Question 21

Substance abuse and schizophrenia

Answer 21

• Maternal substance abuse, and in particular, smoking is a risk factor
• Paternal and Maternal tobacco use has been associated with increased risk of schizophrenia
• Excessive alcohol intake increases the risk of schizophrenia

Question 22

Mesolimbic dopamine pathway

Answer 22

• Evidence from pharmacological studies reveal
biochemical differences in the brains of people
diagnosed with Schizophrenia
• Positive symptoms perhaps the result of increased
activity of dopaminergic synapses in the mesolimbic
pathway

Question 23

Mesolimbic dopamine pathway - chlorpromazine

Answer 23

• Chlorpromazine is an antipsychotic drug that
dramatically reduces the positive symptoms of
schizophrenia
• These drugs are antagonists for D2 and D3 dopamine receptors

Question 24

Mesolimbic dopamine pathway - result of too much dopamine

Answer 24

• Mesolimbic pathway (VTA to the NAC) is a vital link in the process of reinforcement
• Agonist drugs for this pathway (Cocaine, L-DOPA)
strongly reinforce behaviour and produce the positive
symptoms of schizophrenia
• These effects are related. If reinforcement mechanisms are activated at an inappropriate time, then behaviours such as delusional thoughts might be reinforced – this could be associated with paranoia.

Question 25

Consequences of long-term drug treatment of schizophrenia

Answer 25

• antipsychotic drugs can have serious side effects. For example, if you block dopamine transmission, you can end up with symptoms resembling Parkinson’s disease (slowness in movement, weakness, lack of facial expression). This makes sense, as you may recall that Parkinson’s results in the death of cells that release dopamine.
• Another side effect that can occur is Tardive Dyskinesia (TD). TD is a movement disorder that is characterized by involuntary movements of the head and neck (opposite of Parkinson’s disease). It may occur due to supersensitivity

Question 26

Supersensitivity

Answer 26

refers to the increased sensitivity of neurotransmitter receptors due to compensatory mechanisms from long-term drug use

Question 27

Mesocortical dopamine pathway - antipsychotic medication

Answer 27

• Newer antipsychotic medications (atypical
antipsychotics) do not have as many side effects as
chlorpromazine (classic antipsychotic).
• The newer drugs also seem to reduce the positive,
negative and cognitive symptoms of schizophrenia
• Clozapine is an atypical antipsychotic that blocks D4
receptors in the NAC
• How do atypical antipsychotics work?

Question 28

Mesocortical dopamine pathway - hypofrontality

Answer 28

• Converging evidence suggests that the negative and
cognitive symptoms of schizophrenia are the result of
brain abnormalities in the prefrontal cortex (the target of the mesocortical pathway)
• Negative symptoms caused by hypofrontality:
decreased activity in the dorsolateral prefrontal cortex
• This hypofrontality might also be related to the
hyperactivity in the mesolimbic pathways responsible for positive symptoms (dlPFC exerts inhibitory control on the mesolimbic pathway normally)

Question 29

Mesocortical dopamine pathway - typical antipsychotics

Answer 29

• Classic antipsychotics do not reduce cognitive and
negative symptoms of schizophrenia
• One of the causes of negative and cognitive
symptoms is decreased activation of dopamine
receptors in the PFC, so drugs that block dopamine
receptors would, if anything, make symptoms worse

Question 30

Mesocortical dopamine pathway - atypical antipsychotics

Answer 30

• Atypical antipsychotics increase dopaminergic activity in the PFC and decrease dopaminergic activity in the mesolimbic system
• Aripiprazole is a partial agonist. This means it has a very high affinity for a particular receptor, but activates that receptor less than the normal ligand (NT does).
-> Therefore, it can serve as an agonist in regions of low concentration of the normal ligand (PFC), but as an antagonist in regions of high concentration (mesolimbic system)

Question 31

The role of glutamate in schizophrenia

Answer 31

• Some studies suggest that decreased glutamate activity, resulting in hypofrontality, may contribute to the cognitive and negative symptoms of schizophrenia
• Reduced concentration of glutamate in the CSF of those with schizophrenia
• PCP (indirect antagonist for glutamate NMDA receptors) can produce cognitive and negative symptoms in those who are not diagnosed with schizophrenia. It suppresses activity of several brain regions, including the dlPFC.
• PCP also reduces level of dopamine utilization in dlPFC