Schizophrenia Flashcards
What are the 5 positive symptoms of SCZ? (overlaps with psychosis symptoms)
What are positive symptoms characterised by?
Why are they called positive symptoms?
What are negative symptoms characterised by?
What are the 4 negative symptoms of SCZ?
What are negative symptoms?
- Delusions - false beliefs
- Hallucinations - disturbance of sensory perception
- Disorganised thinking/speech
- Disorganised behaviour - meal planning, personal hygiene
- Lack of insight - unaware delusions aren’t real
Abnormal thoughts, perceptions, behaviour & language
Gain of symptoms - not seen in healthy people
Restrictions in emotional expression (intensity & range), communication, body language, interests & normal activities
- Blunted effects - decreased emotional expression, immobile facial appearance, reduced eye contact/body language
- Alogia - reduced speech - less fluid
- Avolition - lack motivation, spontaneity & initiative
- Anhedonia - lack pleasure/interest
Deficit in types of behaviour - loss of function
What happens in cognitive function in SCZ patients?
What do they lead to?
What is poor working memory linked to?
How can cognitive impairment in SCZ be caused?
Impairments of attention, working memory, learning, speech & motor speed
Impairment of skills & diminished functional capacity
Dysfunction of dorsolateral prefrontal cortex - inefficient to use it
Genetically - use for testing
What are the causes of psychosis? 9
What is SCZ?
Therefore what is a method of treating SCZ patients?
What does this not treat?
What are the onset trends?
What does an earlier age of onset mean about the disorder?
What 3 types of symptoms are looked at for SCZ diagnosis?
SCZ, BPD, severe stress/anxiety, severe depression, postnatal psychosis, lack of sleep, Encephalitis (brain inflammation), drug abuse, alzheimer’s
Form of psychosis (symptom) - but psychosis occurs in other diseases
Anti-psychotics - symptoms can be controlled
Severe loss of cognitive function & negative symptoms (only treats positive ones)
Symptoms begin in late teenage years/early 20s, more frequent in women but men have a more severe/earlier onset
More severe symptoms, more frequent & intense negative symptoms & more severe loss of cognitive function & symptom relapse
Positive, negative symptoms & cognitive deficits
What are the 6 criteria in the DSM-V for diagnosing SCZ?
What happens to patients who don’t show as many positive symptoms as negative/cognitive ones?
Why is there a high mortality/morbidity rate?
A: 2+ positive/negative symptoms >1 month (hallucinations, delusions, disorganised speech, anhedonia)
B: Functioning level decreased work, personal, relationships, care
C: Symptoms of disorder last >6 months
D: Excluding schizo-affective disorders (BPD, unipolar)
E: Symptoms not attributed to drug/medication use
F: 1 month of hallucinations/delusions if have pre-existing autism spectrum disorder
Long progressive deterioration & anti-psychotics don’t work
5-10% suicide rate
What environmental factors play a role? 4
With what relations is scz most common?
What does this suggest?
What are the two neurotransmitter systems involved in SCZ?
Is ETC a suitable therapy for scz?
- Urban populations more affected than rural
- Obstetric complications - Higher prevalence in pre-mature births, low birth weight, pre-eclampsia (high blood pressure), resuscitation at birth
- Prenatal nutritional deficiency
- Drug use
Identical twins 48%, fraternal twins 17%, children 13%, siblings 9%
Environmental and also genetic component
Dopamine (G-coupled) & glutamate (AMPA/NMDA)
No evidence that it works - not effective/recommended - used for depression treatment as relies on excitatory synapses
How do antipsychotic drugs treat psychosis/positive symptoms?
What are first & second generation drugs?
What is the D2 receptor coupled to?
How does Paclitaxel also block D2 receptors?
How is the potency of antipsychotics related to the affinity of D2 receptors?
How does cocaine produce psychosis-like symptoms?
How did the dopamine pathway of scz come about?
Dopamine antagonists - block D2 dopaminergic receptors
1st = chlorpromazine, haloperidol - causes extrapyramidal side effects include tremors, rigidity, dystonia (muscle spasms) & tardive dyskinesia (uncontrollable face movements)
2nd = atypical antipsychotics risperidone - fewer EP side effects & acts on serotonin receptors
clozapine - acts on 5HT2A less EPS but other severe side effects - only used in treatment resistant patients
G i/o - its inhibition allows for stopped inhibition adenylyl cyclase
Blocks Gi protein allowing for same effect
Higher potency = higher affinity
Targets dopamine transporter flooding the synapse with increased levels of dopamine - too much dopamine & activation of D2-receptor leading to psychosis similar state
Discovery of antipsychotics in the 1950s
What are the 4 main dopaminergic pathways, where is dopamine transmitted along & what are they related to?
How does the use of amphetamines or L-Dopa support the dopamine hypothesis?
How does the use of anti-psychotics relate?
What was the original hypothesis for why scz occurs?
What has been observed now?
What could this mean?
- Mesolimbic - dopamine transmitted from ventral tegmental area VTA (midbrain) to ventral striatum (includes NAc) - reward, pleasure
- Mesocortical - VTA to prefrontal cortex - executive functions
- Nigrostriatal - Substantia nigra (zona compacta) to caudate nucleus & putamen - motor function, reward & associative learning
- Tubero-hypophyseal - hypothalamus to infundibular/pituitary gland - controls hypophyseal (secretion hormones & prolactin)
Amphetamines is a monoamine oxidase inhibitor - increases amount of dopamine & mimics scz symptoms
L-Dopa is precursor of dopamine - also increases dopamine levels
Alleviates symptoms caused by amphetamines
Excessive dopamine release & D2-receptor activation
Increased D2-receptor binding
Suggests dopamine dysfunction in scz patients or loss of synapses
How is the NMDA receptor linked to scz?
How are NMDAR autoantibodies linked?
How was NMDAR & scz studied in mice in 1999 by Mohn?
Antagonists (PCP, ketamine) produce psychotic & cognitive abnormalities similar to scz - whereas agonists (D-serine, glycine) improve scz symptoms
Higher numbers of them (bind to NMDAR) seen in psychosis patients - suggesting that they perhaps block the receptor
Reduced NMDAR expression - displays scz symptoms
What are the changes in brain volume in scz patients?
When does this happen?
Is there cell death?
What is in the white matter?
Ventricles enlarged with cerebrospinal fluid, reduced volume of basal ganglia, medial temporal lobe, prefrontal cortex & hippocampus - hence loss of synapses
Preceeds scz - some say it’s progressive but debatable
No - no inclusion bodies, plaques
What are the changes in brain volume in scz patients?
When does this happen?
Is there cell death?
What is in the white matter?
What else is reduced?
Ventricles enlarged with cerebrospinal fluid, reduced volume of basal ganglia, medial temporal lobe, prefrontal cortex & hippocampus - hence loss of synapses
Preceeds scz - some say it’s progressive but debatable
No - no inclusion bodies, plaques
Aberrant/abnormal neurones suggesting disordered cortical neuronal migration
Neuropil (synaptically dense regions), pyramidal neurone size, dendritic arborisations (branching), spine density, synaptic connectivity
if individuals with scz have a reduction in dendritic spines - what does this result in?
Therefore, what are the two neurotransmitters in scz doing?
What does glutamate do in healthy brains?
How can synaptic density be measured & what are the results?
Where are the synapses lost at first?
Fewer glutanatergic synapses & therefore decrease in glutamate function
Glutamate hypofunction & dopamine hyperfunction
Binds to SV2A (synaptic vesicle glycoprotein) involved in neurotransmitter release
PET imaging - more SV2A = higher synaptic density (lost in scz patients as fewer synapses & less glutamate function)
Pre-frontal cortex
How would lower glutamate (NMDA) levels lead to psychosis symptoms?
How was this supported?
Therefore what drugs are required to treat positive symptoms?
What drugs cause psychosis like syndromes?
How do genetics play a part in scz?
What 2 mutations can increase your risk?
Low levels fail inhibit mesolimbic neurones - producing excessive dopamine release
Blocking NMDA receptors in rats in VTA showed dopamine increase in nucleus accumbens
Agonists of NMDAR
PCP/angel dust & ketamine - binding site & block NMDAR
No mendelian genetics (i.e dominant allele) but mix of common & rare mutations can increase the risk of developing scz along with environmental factors
Cacna1a loss of function - cognitive impairment
Neuregulin1 mutation (EGF) leading to hypofunction of glutamate (involved in glutamate signalling pathway)
What is the scz GWAS study?
What do some of these loci relate to?
What is the path to scz? 4
What is the problem with current drugs?
Genome wide associated study - searching genomes & identified 108 scz-associated loci
D2 dopamine receptor mutations (hyperactivity), glutamate receptor mutations (hypoactivity)
- Genes/environmental factors leading to subtle motor/cognitive/social deficits
- Social anxiety, delusions/hallucinations & depression (can be brought on by chronic stress)
- Dopamine dysregulation (can be brought on by drug abuse & mutations of neurotransmitter genes)
- Psychosis
Don’t target negative symptoms so need to find other pathways outside of dopamine/glutamate for positive
