Schizophrenia Flashcards
What is schizophrenia co-morbid with?
depression, excessive nicotine, alcohol and substance use, and an increased risk of cardiovascular disease.
How many commit suicide?
5-10%
What are positive symptoms of schizophrenia?
delusions, hallucinations, thought disorders
What are negative symptoms of schizophrenia?
decreased motivation, diminished emotional expression
What are cognitive deficits of schizophrenia?
impairments in attention, executive function, certain types of memory
What are sensory abnormalities of schizophrenia?
gating disturbances
What are sensorimotor abnormalities of schizophrenia?
eye tracking disturbances
What are motor abnormalities of schizophrenia?
impaire posturing
What was schizophrenia once called?
dementia praecox
What are the 4 A’s of schizophrenia according to Bleuler?
Loosening associations
Autistic/ideosyncratic though and behavior
Ambivalence
Disturbance in affect
What is true about early views of schizophrenia?
positive symptoms were view as accessory or secondary
How do schizophrenics score against controls for cognitive deficits?
1.5-2 SD below the healthy controls and 73% rate as impaired vs 15% of general pop.
98% perform more poorly than predicted by parental educational level. Useful as an at risk predictor.
What happens to cognitive impairments prior to first break?
It gets worse. Ability declines in high school. This could be progressive, sudden shift, or they could start behind and just remain behind.
IQ also drops off from childhood to post diagnosis unlike with others.
What do monozygotic twin studies show about cognitive deficits?
affected twin is poorer than unaffected twin who is poorer than control twins.
Also, high risk children with two affected parents have attention deficits during childhood
How are psychotic features different from cognitive deficits?
They’re not persistent and they can burn out.
What is true about early vs late onset of first episode?
Early (youth) onset have larger deficits on most cognitive measures, but late onset have relatively preserved functions.
They both have deficits in attention, global cognition and IQ, but executive function and psychomotor speed and verbal memory are more affected in youth-onset.
Age of onset predicts severity.
What do measures of cognitive function predict?
Social functioning, employment, treatment adherence, relapse prevention, medical comorbidity.
They do not predict psychotic features.
What cognitive domains are most affected (or best studied) in schizophrenia?
vigilance and attention
verbal memory worse than visual memory
verbal fluency (list of words begins with letter A)
social cognition
working memory (verbal and non-verbal material, also mental rearranging of material)
What is shown about improvement of working memory with age in schizophrenia?
It declines on the same curve as other cognitive problems (or not declines, but fails to improve linearly) from 6-22
What is true about working memory and rewards in schizophrenia?
They have lower WM capacity and faster decay, but normal reinforcement learning so it’s not a reward system disturbance.
ie. they aren’t bad at the task because they don’t care about the reward. Their deficit is due to failure to learn outcomes which is a result of WM.
What area is associated with schizophrenia as a focus of this lecture? How do they know?
Dosrolateral prefrontal cortex as seen in fMRI, network oscillations by EEG, and GABA neurotransmission assessment postmortemly
How was decreased working memory shown in fMRI?
Lack of BOLD response in DLPFC for items present 2 back, but not 1 back.
What increases with working memory load in humans? What is true about schizophrenic patients?
DLPFC Gamma Band Power but these are practically nonexistant in fMRI studies of DLPFC.
I think this means more neurons are firing
What is critical for gamma oscillations and working memory?
Pyramidal neuron-parvalbumin GABA neuron circuitry in the DLPFC layer 3
How does the Pyramidal neuron-parvalbumin GABA neuron circuitry in the DLPFC layer 3 work?
I think there’s excitatory input to the PYR cell which passes through the PV cell and inhibits another PYR cell. This then excites the PV cell some or the original PYR cell. The second PYR cell can also be directly excited by the first.
This is all through glutamate.
What are the principal sources and targets of glutamate neurotransmission in the DLPFC?
In the DLPFC, pyramidal neu- rons (Figure 1C) are the principal source of glutamate neurotransmission, as well as the targets of the majority of glutamate-containing axon terminals.
What increases in the DLPFC in schizophrenia?
Neuronal density.
Increased cell packing density has been interpreted as evidence of a reduction in the amount of cortical neu- ropil, the axon terminals, dendritic spines, and glial processes that occupy the space between neurons.
What is true about dendritic spines in the DLPFC of schizophrenia?
Dendritic spines are the principal targets of excitatory synapses to pyramidal neurons. Although most dendritic spines present are stable in number during adulthood,23 they are subject to a number of neuroplastic changes, such as a loss of their presynaptic excitatory input. In schizophrenia, dendritic spine density in pyramidal neu- rons has been reported to be lower in the DLPFC24,25
How are pyramidal cells different in different layers of DLPFC?
For example, many pyramidal cells in layers 2 to 3 send axonal projections to other cortical regions, pyramidal neurons in layer 5 tend to project to the striatum and other subcortical structures, and pyramidal neurons in layer 6 furnish projections primarily to the thalamus.26 Studies of basilar dendritic spine density on Golgi-impregnated pyramidal neurons in each cortical layer of the DLPFC in the same cohort of subjects found a significant effect of diagnosis on spine density only for pyramidal neurons in deep layer 3 (Figure 2).25,27
In schizophrenia, somal bodies are smaller in deep layer 3, but not layer 5. The decrease indicates fewer dendritic spines
What puts off decline in schizophrenia until adolescence?
Thus, the presence of functionally mature synapses prior to adolescence supports the hypothesis that the excess in excitatory synapse number prior to adolescence might be able to compensate for a molecu- lar based dysfunction of these synapses in individuals with schizophrenia, and thereby forestall the appearance of the clinical features of the illness until synapse num- ber falls below some critical threshold.
What is true about GABA in schizophrenia?
Synthesis and reuptake are lower in the DLPFC
What determines oscillation frequency?
IPSC duration (inhibitory post synaptic current)
What does rhythmic interneuron firing produce?
Synchronized network oscillations.
How is synchrony affected in schizophrenia?
It’s impaired. PV Basket Neuron doesn’t seem to inhibit pyramidal neurons as well.
How is the GABA problem compounded?
1) Lower presynaptic strength of inhibition due to less GABA (less protein that makes GABA in terminals)
2) Lower postsynaptic strength of inhibition due to fewer GABA receptors
3) Cl- Less hyperpolarization due to lower CI- influx when GABA receptors open
What happens during treatment with a GABAa receptor alpha2/3-selective positive allosteric modulator?
More synchrony in DLPFC during short term retention of information for a cognitive task.
Doesn’t look normal but better than maybe first-degree relatives.
What does this lecturer think is hte primary problem in layer 3?
Problem with excitatory drive in pyramidal neurons.
How can primary deficit in the DLPFC account for psychosis?
Spine deficits in the DLPFC are upstream of subcortical hyperdopaminergia and this results in psychosis over time.
Less GABA disinhibits dopamine and causes psychotic impairment.
