Lecture 78: Schizophrenia

Question 1

Age of onset of schizophrenia is typically ________ for women

Answer 1

Later

Question 2

Diagnosis for schizophrenia is based on…

Answer 2

Clinical symptoms

Question 3

Clustered groups of schizophrenia symptoms

Answer 3

Positive, negative, and cognitive

Question 4

Positive symptoms (3)

Answer 4

Hallucinations, delusions, disorganized thinking/speech/behavior

Question 5

Negative symptoms

Answer 5

Alogia (speech poverty), affective blunting, avolition, anhedonia

Question 6

Cognitive symptoms

Answer 6

Attention, memory, verbal fluency

Question 7

Formal schizophrenia dx requires

Answer 7

Several positive symptoms for at least a month + ongoing illness for at least 6 months

Question 8

Describe cognitive abnormalities in schizophrenia

Answer 8

Present prior to onset, pts generally perform below average

Question 9

Why are cognitive symptoms so important?

Answer 9

No pharmacological treatment available, but these symptoms are important for long-term dysfunction

Question 10

Four disorders often confused with schizophrenia

Answer 10

Bipolar manic episodes, schizoaffective, schizophreniform (shorter duration), delusional disorder (less bizarre, often fixed delusions)

Question 11

What symptoms start first? What is this phase called?

Answer 11

Cognitive symptoms; premorbid phase

Question 12

Describe prodromal phase of schizophrenia

Answer 12

“Attenuated psychotic symptoms,” which may include obsessions, sleep problems, negative symptoms, school/relationship trouble

Question 13

What happens at the end of the prodromal phase? What happens next?

Answer 13

Acute, active psychotic symptoms; treatment initiated

Question 14

What is the final phase, describe pos, cog, neg symptoms

Answer 14

Postpsychotic phase: positive symptoms decrease, cognitive symptoms fixed, and negative symptoms still existent, though somewhat better

Question 15

Patients with sustained remission (%). Do patients generally make it back to work?

Answer 15

77%; no

Question 16

Untreated psychosis is related to…

Answer 16

Poorer outcomes

Question 17

Medical co-morbidities of schizophrenia

Answer 17

Suicide, accidents, substance abuse, CV mortality (sedentary, obesity); ~15 year reduction in lifespan

Question 18

Environment risk factors for schizophrenia (7)

Answer 18

Prenatal infections, obstetrical complications, season of birth (winter), place of birth (urban), paternal age, drug use, head injury

Question 19

What is the largest risk factor for developing schizophrenia? Heritability (%)?

Answer 19

Family history; 80%

Question 20

Describe the Threshold Liability Model

Answer 20

Multiple genetic factors contribute –> the overall number inherited place you closer from a critical number of factors to reach the disease threshold

Question 21

What study methodology has been used to examine genetic risks for schizophrenia? What are two important findings from this work?

Answer 21

GWAS; 1. Risk factors are shared across SCZ, BD, and MDD; 2. DNA deletions and duplications are enriched in SCZ in patients (STRONG influence on risk)

Question 22

T/F: De novo mutations are enriched in schizophrenia

Answer 22

False: no increase in over all rate of mutations

Question 23

Where are de novo mutations found in schizophrenia? What about clinical presentations…

Answer 23

Synaptic genes; more common in patients who do poorly in school

Question 24

Three take home messages about genes and schizophrenia and final point

Answer 24

1. Rare, risk-increasing CNVs; 2. Common SNPs by GWAS; 3. Very rare SNPs by deep sequencing –> Highly polygenic participate in increasing individuals risk

Question 25

DA hypothesis (what it’s based on)

Answer 25

Based on fact that antipsychotic drugs block DA receptors and enhancing DA –> schizophrenic symptoms

Question 26

Positive symptoms related to what DA system?

Answer 26

Overactivity of mesolimbic system

Question 27

Glutamate hypothesis (5 supporting facts)

Answer 27

PCP and ketamine –> psychosis; increased sensitivity of schizophrenia to NMDA antagonists; dementia in schizophrenics; genetic risk in glutamate receptor genes; glutamate abnormalities found in patient cells

Question 28

Glutamate hypothesis take home…

Answer 28

Decreased inhibition

Question 29

Macroscopic changes (3)

Answer 29

Smaller hippocampus, amygdala, cerebellar vermis; enlarged ventricles; lower brain weights

Question 30

Histological changes (3)

Answer 30

Disarray of pyramidal cells in CA1/CA2 in hippocampus, increased neuronal density in PFC; reduced dendritic spines

Question 31

Neuroimaging functional finding

Answer 31

Reduced prefrontal activation during executive cognitive functioning = hypofrontality

Question 32

Neurodevelopmental hypothesis (background + hypothesis)

Answer 32

Structural abnormalities prominent in neurodevelopmental disorders and enriched in schizophrenia; SCZ might be related to an early defect –> later pathology

Question 33

What are the early defects of the neurodevelopmental hypothesis (3) and what is a histological correlation

Answer 33

Problems myelinating, WM abnormalities, problems with synaptic pruning; fewer dendritic spines