How is the hippocampus altered in schizophrenia?
Disorganised pyramidal cell layers of the hippocampus (usually organised, allowing efficient inputs from entorhinal cortex and outputs to brain regions) leading to memory abnormalities, etc.
What genes of the glutamatergic system are linked to schizophrenia?
Genes linked to NMDA function: - ErbB4 neuregulin receptor (regulates kinetic properties of NMDARs, induces NMDAR activation) - RGS4 (molecule found in PSD, inhibits mGluR5s)
What four pathways to dopaminergic neurones project through?
1 - mesolimbic pathway 2 - mesocortical pathway 3 - nigrostriatal pathway 4 - tuberoinfundibular pathway
What are thought disturbances defined as?
Difficulty keeping track of thoughts , thoughts drifting from one idea to another
What prefrontal cortex structural abnormalities are associated with schizophrenia?
- enlargement of cerebral ventricles by ~20% - decrease in PFC volume (therefore neuronal loss - ⬇️ dendritic field and ⬇️ spine density) - decrease in cortical grey matter by ~2%
What neurotransmitters are implicated in schizophrenia?
Dopamine and glutamate
What is the “flat effect” of schizophrenia defined as?
A lack of emotional reactivity (i.e. no emotional ups or downs)
What can schizophrenia symptoms be classified as?
1) POSITIVE symptoms - levels are above normal 2) NEGATIVE symptoms - levels are below normal
What are the DA receptor families?
- D1 family (D1 + D5): postsynaptic GPCRs that ✅ adenylyl cyclase - D2 family (D2, D3 + D4): pre/post synaptic GPCRs that
What is the evidence for a genetic cause for schizophrenia?
% lifetime risk of developing schizophrenia if: no/distant relative = 1-2% secondary relative = 2-6% primary relative = 6-17% monozygotic twin = 48%
What are the brain regions involved in schizophrenia?
The prefrontal cortex and the hippocampus
What is the prodromal period of schizophrenia?
A symptomatic period starting years before first acute schizophrenic episode occurs
What is avolition defined as?
A lack of motivation
What genes are implicated in schizophrenia?
- schizophrenia is a developmental disorder therefore genes linked to development are implicated, e.g. genes linked to myelination, atonal guidance and neuronal migration - genes linked to synaptic plasticity, e.g. neuregulin function (alters activity of NMDARs and AMPARs) - genes linked to DA metabolism and DA signalling, e.g. COMT (alters DA release)
What is the dopamine hypothesis of schizophrenia? Is this hypothesis true?
Schizophrenia is a result of abnormalities to the DA system, i.e. an abnormal increase in central DA release There is evidence for this hypothesis, but it is too simplified to explain schizophrenia
What can a psychotic episode be characterised by?
1) disturbances in reality and perception 2) impaired cognitive functioning 3) inappropriate affect
Is there a simple genetic inheritance of schizophrenia?
No, there is not one gene/gene defect that causes schizophrenia
What is the nigrostriatal DA pathway? How is this affected in schizophrenia?
DA neurones from the substantia nigra projecting to the dorsal striatum This is part of the extrapyramidal motor system, involved in initiation and control of movement - D2 receptors in the SN are blocked by antipsychotics, leading to a decrease in motor control and Parkinson’s symptoms
What is alogia defined as?
“Poverty of speech”, i.e. a general lack of additional, unprompted contributions to normal speech
What factors allow a schizophrenia diagnosis?
1 - two or more key positive/negative symptoms 2 - social/occupational dysfunction 3 - these disturbances much be continuous for at least 6 months 4 - drug abuse must be excluded
What is the tuberoinfundibular DA pathway? How is this affected in schizophrenia?
DA neurones projecting to the hippocampus and anterior pituitary. Antipsychotic drugs acting on this pathway linked to unwanted milk production side effect. (DA released into the perivascular spaces here is taken up by capillaries and transported to pituitary, where it acts on cells to inhibit prolactin release and regulate milk production and lactation)
Give four examples of positive symptoms of schizophrenia
Hallucinations, delusions of grandeur/persecutions, thought disturbances and bizarre behaviour
When are symptoms of schizophrenia first seen?
Disease onset is ADOLESCENCE but may see PRODROMAL SYMPTOMS (early symptoms indicating disease onset before specific symptoms occur)
What is the glutamate hypothesis of schizophrenia? What is the evidence for this hypothesis?
Schizophrenia linked to hypo function in the glutamatergic system.
