Schizophrenia Flashcards
Schizophrenia
- Reduces life expectancy by how many years?
Mental illness characterized by positive symptoms (addition of atypical exp and behavs), negative symptoms (loss/reduction in normal behavs), and cog dysfunction
- 10-20 years shorter than general pop
Positive symptoms of schizophrenia (3)
HALLUCINATIONS:
- Sensory exp in absence of stimulus (auditory most common, voices making commands and provide negative commentary on one’s thoughts/exps)
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DELUSIONS:
- Strongly held false beliefs, not changed even w/ conflicting evidence
- Persecutory: Believing others are out to harm them
- Referential: Believing gestures, comments, other cues have special meaning directed towards them
- Grandiose: Exaggerated sense of power, talent, knowledge, importance
- Control: Believing mind/body is being controlled by an outside source
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DISORGANIZED THINKING AND SPEECH:
- Difficulty processing thoughts logically and coherently
- Derailment/loose associations: Speech tends to slip off track, ideas are loosely related
- Clang associations: Choosing words based on sounds rather than meaning
- Incoherence: No discernible connection between words
Negative symptoms of schizophrenia (4)
What is catatonia (disorganized behaviour)? Is it a positive or negative symptom?
ALOGIA (Poverty of speech):
- Reduced spontaneous speech, reflects disruption in maintaining a line of thought
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BLUNTED AFFECT (Flat affect):
- Reduction or absence of emotional responsiveness
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AVOLITION:
- Lack of motivation to initiate and complete purposeful tasks
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ANHEDONIA:
- Lack of pleasure or interests in activities that were once enjoyable
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- Addition of strange, often repetitive or extreme behavs
- Loss of movement and responsiveness
- Both positive and negative
DSM-5 schizophrenia diagnosis requirements
- 2 or more of symptoms (delusions, hallucinations, disorganized speech, disorganized/catatonic behaviours, negative symptoms)
- But one must be delusions, hallucinations or disorganized speech
- Symptoms must last for at least 1 months and continuous disturbance for at least 6 months
Schizophrenia age of onset
Risk factors (6)
Late teens/early adulthood
- Women: 25-35 years old
- Men: 18-25 years old
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- Polygenic (genetic) factors
- Prenatal low vitamin D
- Prenatal viral infections
- Exposure to trauma/stress
- Urban place of birth/upbringing
- Cannabis use and variation in COMT gene (slower at breaking down dopamine in synapse)
Dopamine hypothesis (Schizophrenia)
- Evidence (2)
- Early models proposed that dysfunction of what pathway underlies positive symptoms + evidence (3)
- Recent models proposed what + evidence (3)
Hyperactive dopaminergic signal transduction leads to positive symptoms of schizophrenia
- Mesostriatal DA signaling is involved in marking salience of stimuli, so excess tags normally irrelevant internal/external stimuli and makes it harder to filter out
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Evidence:
- Amphetamine and other compounds that increase extracellular levels of dopamine can induce psychotic symptoms similar to schizophrenia
- Clinical effectiveness of typical antipsychotics was directly related to their ability to block dopamine (D2) receptors
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Dysfunction of mesolimbic pathway
- Seizures localized to limbic areas sometimes elicit psychotic symptoms
- Electrodes implanted in schizophrenia patients showed increased activity in limbic regions during active psychosis
- In rats, injections of antipsychotics into nucleus accumbens got rid of amphetamine-induced behavs
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Dysfunction of nigrostriatal pathway
- Meta-analysis of PET studies show increase in DA synthesis and release in dorsal striatum during psychosis
- Resting state fMRI studies show greater activity in dorsal striatum is correlated w/ psychotic symptoms in schizophrenia
- Dopaminergic dysfunction in schizophrenia is more within dorsal striatum (caudate and striatum) than ventral striatum (nucleus accumbens)
Glutamate hypothesis of schizophrenia
- Evidence (3)
Schizophrenia involves hypofunction of NMDA receptor, reducing activity of GABAergic interneurons
- Leads to disinhibition of glutamatergic neurons that project to midbrain and increase activity of dopaminergic neurons there
- Prefrontal cortex and hippocampus are potential sites for source of altered glutamatergic function
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- NMDA receptor antagonists produce effects that closely resemble symptoms seen in schizophrenia
- Longer-term administration of ketamine (NMDA receptor antagonist) to rats produce cognitive deficits similar to schizophrenia
- NMDA receptor agonists (glycine, D-serine) ameliorated residual positive and negative symptoms when combined w/ antipsychotic treatment
Enlargement of ventricles usually seen where in schizophrenia? (2)
Reduced metabolic activity found in which part of brain? Term for this?
Left superior temporal gyrus
Medial temporal lobe
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Bilateral frontal cortex
Hypofrontality; underlies negative and cognitive symptoms
Triple network model of psychopathology (schizophrenia):
- Default mode network (DMN)
- Frontoparietal network (FPN)
- Salience network (SN)
Compare normal functioning vs Dysfunction
DMN: Self-related, internally oriented thoughts (Posterior cingulate, medial prefrontal cortex)
FPN: Executive functioning (Dorsolateral PFC, posterior parietal cortex)
SN: Salience processing (Anterior insula, dorsal ACC)
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Normal:
- DMN decreases in activity and FPN increases in activity during goal-directed behav
- SN facilitates switching between FPN and DMN (disengage from self-referential mental processes to respond to current task goals)
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Dysfunction:
- Reduced functional connectivity between and within SN, FPN, and DMN; FPN increases in activity but DMN doesn’t decrease
- Leads to inappropriate assignment of saliency (leads to referential delusions, misattribution of internally generated thoughts)
Schizophrenia cognitive dysfunction symptoms
- Processing speed
- Working memory
- Attention
- Declarative memory
- Social cognition
PROCESSING SPEED:
- Speed at which an individual can perceive a given stimulus, interpret info, and produce response
- Mental processing and behav execution esp impaired (seen in negative symptoms)
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WORKING MEMORY:
- Limited capacity system involving temporary storage and manipulation of info necessary for complex processes including comprehension, learning, reasoning; 3-4 capacity
- Involves central executive (attentional controller; dorsolateral PFC), visuospatial sketchpad (short teem storage buffer for visual info), phonological loop (short term storage buffer for verbal info), episodic buffer (integrates and store multi-modal info, links WM to long term memory; inferior frontal and posterior parietal regions for all buffers)
- Frontoparietal regions important for WM, parietal cortex specifically for WM capacity limitation
- Central executive impacted in schizophrenia (reduced activity in dorsolateral PFC and dorsal parietal cortex); intact ventral parietal cortex and ventrolateral cortex shows phonological loop is intact
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ATTENTION:
- Ability to focus awareness on relevant stim and shift awareness when needed
- Low global alertness leads to internal mind wandering and related to difficulty inhibiting DMN
- Impaired attentional control when focusing on low-salience stimuli in presence of highly salient stim; dependent on FPN
- High selective attention even on unnecessary stim; Hahn et al (2012) study shows schizo ppl struggled in task when four locations cued compared to one, but no problem with healthy controls; Any impairment most likely from psychosis
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DECLARATIVE MEMORY:
- Episodic memory impairment and deficits in recall
- Relational memory (relationships between items/elements) more impaired than item memory (distinctive features of individual items); Relational relies on dorsolateral PFC but less activity in schizo
- Ragland et al (2015) study w/ relational and item-specific encoding (RiSE) paradigm shows item recognition was worse following relational encoding + overall worse in associative recognition test phase
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SOCIAL COGNITION:
- Processes that are involved in perception, encoding, storage, retrieval, and regulation of information about other ppl and ourselves
- Domains include emotion processing (identify emotions in others, manage own emotions), social perception (identify social roles, rules, context from nonverbal cues), attributional bias/style (way in which we explain causes and make sense of social events/interactions), mentalizing (represent mental states of others, make inferences about their intentions/beliefs/emotions)
- Includes medial prefrontal cortex, fusiform gyrus, amygdala
- Emotion processing (esp identifying facial expressions), mentalizing, and social perception (misinterpretation of others’ intent, social withdrawal, impaired daily social functioning) impaired
Schizophrenia treatments:
- Typical antipsychotics (haloperidol, chlorpromazine)
- Atypical antipsychotics (clozapine, risperidone, olanzapine)
- NMDA receptor co-agonists (glycine, D-serine)
- Transcranial magnetic stimulation (TMS)
- Cognitive remediation (CR)
TYPICAL:
- Blocks dopamine D2 receptors
- No effect on negative on cog symptoms; mainly positive only
- Has side effects like weight gain, muscle stiffness, tardive dyskinesia, Parkinsonian like symptoms
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ATYPICAL:
- Blocks dopamine D2 and serotonin 5HT2A receptors
- Less effective than typical antipsychotics and more likely to cause metabolic side effects (weight gain, high BP, insulin resistance); but less likely to cause Parkinsonian like symptoms
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- Targets glutamate system
- Mixed results in effectiveness
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- Applies alternating magnetic fields to induce electrical current to stimulate brain in frontal or temporoparietal cortices
- Frontal shows limited success in reducing symptoms but temporoparietal has some success
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- Behavioural training intervention to improve cognitive functioning
- Compensatory training: Learning strats to compensate for cognitive deficits (like use of external memory aids)
- Restorative training: Techniques aimed at enhancing/restoring cognitive function (like computerized paper-and-pencil exercises of varying length and intensity)
- Small to moderate effects but unclear if improvements sustained or work in daily activities
Subcortical structures and cognitive dysfunction in first episode schizophrenia (Fan et al., 2019)
Are deficits in subcortical grey matter kinked to neurocognitive dysfunction w/ first-episode schizophrenia
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- Reasoning/Problem solving and Positive symptoms of psychosis positively correlated w/ amygdala and nucleus accumbens volume
- Dose of antipsychotic medication was +vely correlated w/ vol of amygdala, nucleus accumbens, caudate, putamen, pallidun
Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills? (Moritz et al,. 2017)
Do lack of motivation and negative attitudes towards cog assessment result in poorer secondary neuropsychological performance?
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Performed worse than all controls on tested neurocognitive domains BUT displayed more subjective momentary impairment, more fears about outcome, and less motivation
