Basic science of schizophrenia Flashcards
What are some aspects of schizophrenia that can be modelled in animals?
Locomotor changes, sensory gating abnormalities, impaired social interactions, alterations in neurotransmitter levels or actions, changes in cellular morphology or function
What can happen to speech in people with SZ?
- Loose associations - rapidly shifting between unrelated topics
- Perseveration - repeating the same things over and over again
- Use of rhyming words without reason
What actions can be affected in people with SZ?
- Difficulty starting or finishing tasks
- Behaviours that appear bizarre or lack purpose
- Unpredictable or inappropriate emotional responses
What impairment in SZ predicts language disturbances?
- Working memory and executive function are impaired in SZ
- fMRI studies reveal task dependent abnormalities in prefrontal activity
What is the link between the DISC1 gene and SZ?
- Located in a chromosomal region that contains susceptibiltiy genes for psychiatric illness in several populations
- Truncates (and inactivates) a gene called DISC1
- Affected members have greatly increased risk of psychiatric disorders including SZ but also depression and bipolar
What is the function of DISC1?
The DISC1 gene is necessary for pyramidal cell migration
What do subjects with induced expression of mutant human DISC1 show?
Hyperactivity, abnormal social behaviour, ventricular enlargement and reduced gamma synchrony
What are the features of the neurodevelopmental hypothesis of schizophrenia?
Hyperconnectivity, synaptic pruning failure, aberrant neuronal migration and synaptic changes
What are endophenotypes?
Simple, quantifiable and heritable biological or behavioural traits that segregate with an illness
What is the role of developmental oxidative stress in SZ?
Oxidative stress in cortical neurons causes altered parvalbumin interneurons which causes an excitation-inhibition imbalance, leading to altered EEG oscillations and cognitive deficits
Neonatal hippocampal lesions in rats causes what in adolescence?
Hyperactivity, hypersensitivity to stress, working memory deficits, reduced pre-pulse inhibition (PPI), reduced parvalbumin staining, changes in DA activity, altered cortical E/I balance
SZ is associated with abnormal early processing of sensory information, particularly auditory. What could this be related to?
- Difficulties in filtering out irrelevant stimuli
- Attentional deficits Impairments in language processing
What is sensory gating?
Neurological processes of filtering out redundant or unnecessary stimuli in the brain from all possible environmental stimuli
What proportion of people with SZ and people without SZ showed problems with sensory gating?
- 90% of people with SZ
- 8% of people without SZ
What is pre-pulse inhibition (PPI)?
Neurological phenomenon in which a weaker pre-stimulus (pre-pulse) inhibits the reaction to a subsequent strong reflex-eliciting stimulus (pulse), often using the startle reflex
What drug has been shown to reverse the impairment in PPI in rodents?
Haloperidol (DA D2 antagonist)
What is the problem with reduced PPI in SZ?
It is not specific to SZ, PPI deficits are seen in HD as well
What is mismatch negativity?
Mismatch negativity is a negative component of the event-related response in an EEG signal, elicited by any perceptible change in some repetitive aspect of an auditory stimulation e.g. stimulus pitch
How is mismatch negativity affected in SZ?
- Reduced in SZ
- Varies with symptom progression, i.e. chronic SZ there will be greater reduction in MMN compared to recent onset SZ
What is the P300 wave?
- The P300 wave is an event-related potential (ERP) component elicited in the process of decision making.
- It is considered to be an endogenous potential, as its occurrence links not to the physical attributes of a stimulus, but to a person’s reaction to it.
- It is modulated by attention
How is the P300 wave affected in SZ?
Reduced in SZ
What kind of drugs can cause psychosis via dopamine pathways?
Amphetamines can elevate brain DA levels and cause psychosis (positive symptoms of SZ)
What is some of the evidence for and against the DA hypothesis of SZ?
Evidence for:
- Anti-psychotics block D2 receptors
- Drugs such as amphetamines elevate brain DA levels and cause psychosis
- Elevated D2 receptor levels in people with SZ
Evidence against:
- DA-inhibiting drugs modify DA levels within minutes but can take much longer to be effective as anti-psychotics
- Abnormalities in other systems e.g. GABA and glutamate
What is thought to underlie the positive symptoms of SZ?
Hyperactivation of both the mesolimbic and nigrostriatal pathways
