Lecture 78: Schizophrenia Flashcards
Age of onset of schizophrenia is typically ________ for women
Later
Diagnosis for schizophrenia is based on…
Clinical symptoms
Clustered groups of schizophrenia symptoms
Positive, negative, and cognitive
Positive symptoms (3)
Hallucinations, delusions, disorganized thinking/speech/behavior
Negative symptoms
Alogia (speech poverty), affective blunting, avolition, anhedonia
Cognitive symptoms
Attention, memory, verbal fluency
Formal schizophrenia dx requires
Several positive symptoms for at least a month + ongoing illness for at least 6 months
Describe cognitive abnormalities in schizophrenia
Present prior to onset, pts generally perform below average
Why are cognitive symptoms so important?
No pharmacological treatment available, but these symptoms are important for long-term dysfunction
Four disorders often confused with schizophrenia
Bipolar manic episodes, schizoaffective, schizophreniform (shorter duration), delusional disorder (less bizarre, often fixed delusions)
What symptoms start first? What is this phase called?
Cognitive symptoms; premorbid phase
Describe prodromal phase of schizophrenia
“Attenuated psychotic symptoms,” which may include obsessions, sleep problems, negative symptoms, school/relationship trouble
What happens at the end of the prodromal phase? What happens next?
Acute, active psychotic symptoms; treatment initiated
What is the final phase, describe pos, cog, neg symptoms
Postpsychotic phase: positive symptoms decrease, cognitive symptoms fixed, and negative symptoms still existent, though somewhat better
Patients with sustained remission (%). Do patients generally make it back to work?
77%; no
Untreated psychosis is related to…
Poorer outcomes
Medical co-morbidities of schizophrenia
Suicide, accidents, substance abuse, CV mortality (sedentary, obesity); ~15 year reduction in lifespan
Environment risk factors for schizophrenia (7)
Prenatal infections, obstetrical complications, season of birth (winter), place of birth (urban), paternal age, drug use, head injury
What is the largest risk factor for developing schizophrenia? Heritability (%)?
Family history; 80%
Describe the Threshold Liability Model
Multiple genetic factors contribute –> the overall number inherited place you closer from a critical number of factors to reach the disease threshold
What study methodology has been used to examine genetic risks for schizophrenia? What are two important findings from this work?
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)
T/F: De novo mutations are enriched in schizophrenia
False: no increase in over all rate of mutations
Where are de novo mutations found in schizophrenia? What about clinical presentations…
Synaptic genes; more common in patients who do poorly in school
Three take home messages about genes and schizophrenia and final point
- Rare, risk-increasing CNVs; 2. Common SNPs by GWAS; 3. Very rare SNPs by deep sequencing –> Highly polygenic participate in increasing individuals risk
DA hypothesis (what it’s based on)
Based on fact that antipsychotic drugs block DA receptors and enhancing DA –> schizophrenic symptoms
Positive symptoms related to what DA system?
Overactivity of mesolimbic system
Glutamate hypothesis (5 supporting facts)
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
Glutamate hypothesis take home…
Decreased inhibition
Macroscopic changes (3)
Smaller hippocampus, amygdala, cerebellar vermis; enlarged ventricles; lower brain weights
Histological changes (3)
Disarray of pyramidal cells in CA1/CA2 in hippocampus, increased neuronal density in PFC; reduced dendritic spines
Neuroimaging functional finding
Reduced prefrontal activation during executive cognitive functioning = hypofrontality
Neurodevelopmental hypothesis (background + hypothesis)
Structural abnormalities prominent in neurodevelopmental disorders and enriched in schizophrenia; SCZ might be related to an early defect –> later pathology
What are the early defects of the neurodevelopmental hypothesis (3) and what is a histological correlation
Problems myelinating, WM abnormalities, problems with synaptic pruning; fewer dendritic spines
