essay plans Flashcards
describe and give examples of the 3 different types of symptoms of schizophrenia
negative (come first):
- absence of normal behaviours
- reduced emotional response, speech poverty, lack of initiative, anhedonia, social withdrawal
cognitive (second): reduced: sustained attention, psychomotor speed (fluent movement of the arms and legs), abstract thinking, problem-solving.
Weinberger 1988: ALL associated with frontal lobe HYPOfunction: decreased performance in Stroop tests (attention), sensory-motor gating tasks - P50 and PPI, oculomotor function
positive (last):
- additional behaviours
- though disorders, delusions, hallucinations
- though disorders: disorganised/irrational thinking, difficulty w though arrangement, jumping from topic to topic, rhyme over meaning
- delusions: beliefs contrary to fact –>
Persecution: false beliefs that others are plotting and conspiring against you
Grandeur: false beliefs about one’s power/ importance - god-like
Control: related to persecution - he/she is being controlled by others
Describe the structural differences of schizophrenic brains
Weinberger and Wyatt (1982)
CT scan of matched aged sample of schizophrenics vs healthy
- schizophrenic lateral ventricles 2x the size of controls
- but had reduced grey matter in temporal, frontal lobes and hippocampus
–> faulty cellular arrangement in the context and hippocampus
Discuss the heritability of schizophrenia
- twin and adoption studies lead to - yes there is a genetic component
- no actual schizophrenic causing genes
- but instead - multiple that increase susceptibility which can be triggered by environment
- DISC1 gene = disrupted in schiz
- involved in regulation of neurogenesis, neuronal migration and postsynaptic density on excitatory neurons + mitochondria function
- ^ chance by factor of 50
- as well as BD and ASD
- children with OLDER father = more likely to develop schizophrenia
- mutations in cells that produce sperm
- divide every 16 days so more time = more chance of mutation
statistics of schizophrenia
general pop: 1%
DZ: 17%
MZ: 48%
Both parents schizophrenic = 46%
describe the neurodevelopmental theories of schizophrenia with evidence
the ‘early’ neurodevelopmental model:
- early life events (prenatal) e.g. infection–> cause deviations from normal neurodevelopment –> these lie dormant until the brain matures + the affected systems are called into operation
Walker et al: Home movies 1994,96
- independent observers examined behaviour of families with schiz child
- subsequent schizophrenics –> ^ negative facial expressions and ^ abnormal movements
Schiffman 2004: Danish lunch tapes
- blind raters –> subsequent schizophrenics = less sociability and deficient psychomotor functioning
SUGGEST DEVIATIONS IN BRAIN DEVELOPMENT
CORRELATIONAL
The ‘late’ neurodevelopmental model: Feinberg ‘82/3
- abnormality/deviations in adolescence when synaptic pruning takes place
The ‘two-hit’ model: Fatemi & Folsom 2009 & Kehavan and Higarty 1999
- COMBINES THE TWO
- atypical development at both early brain development and adolescence
- early development –> dysfunction in specific neural networks = premorbid signs
- adolescence –> excessive synaptic pruning and loss of plasticity = emergence of symptoms
describe the neurochemistry theories of schizophrenia with evidence
DOPAMINE
The dopamine (DA) hypothesis):
- schiz is caused by abnormalities is DA functioning in the brain
- ^ overactivity of DA in mesolimbic system = positive symptoms
- v underactivity of DA is the mesocortical system = negative and cognitive symptoms
EVIDENCE:
- DA agonist drugs = schiz like symptoms e.g. amphetamine, cocaine, methylphenidate and L-DOPA –> symptoms can be reduced by antipsychotic drugs - ^ argument that the drugs block DA receptors
- chlorpromazine (CPZ) is a DA antagonist/inhibitor - first antipsychotic –> dramatic effects on schiz
- typical antipsychotics followed - D1-type family and D2-type family
- ^ all block D2 receptors
- IBZM = radiotracer that binds with the same D2 receptor as DA
- measured displacement of IBZM after amphetamine in striatum
- ^ displacement = more DA
- more DA in striatum correlated with positive symptoms
BASICALLY DRUGS ARE GOOD EVIDENCE
PROBLEMS:
- explains only positive symptoms
- the drugs that have weaker anti-dopamine mechanisms work better?
- negative symptoms = underactivity is mesocortical so it underactivity rather than over
describe the neurochemistry theories of schizophrenia with evidence
Glutamate
- glutamate = major excitatory neurotransmitter in the central nervous system
- many brain neurones - ALL from cerebral cortex = use glutamate as neurotransmitter
- balanced with GABA - the main inhibitory neurotransmitter
- NMDA receptor (Glutamate receptor) = ionotropic, at rest blocked by magnisum at open = calcium influx
- activation = learning and memory –> too much = excitotoxic (cell death)
- critical for neural survival, migration, plasticity
- HYPOTHESIS: schiz is due to NMDA receptor hypofunction = explains why there are treatment-resistant negative symptoms, onset is early in adulthood, association with structural changes and cognitive deficits
- explains all 3 symptoms, accounts for lack of effectiveness of DA
- hypofunction NMDA receptors account of excessive DA release in mesolimbic and reduced in mesocortical
- when glutamate is low GABA interneuron isn’t activate to decrease release of dopamine - explains pos
- loss of glutamine = loss of cortical function = negative functions
EVIDENCE:
- PCP drug and Ketamine = pos, neg, cog symptoms of schiz
- BOTH are NMDA receptor antagonists
- glutamate agonists (mimic) = improve pos and neg symptoms
- animal studies and genome studies
- ket and PCP symptoms = caused by decrease in metabolic activity of frontal lobes
- PCP to monkeys 2x day 2 weeks
- task that relies on PFC function = monkeys = severe deficit if PCP
describe the neurochemistry theories of schizophrenia with evidence
neuroinflammatory hypothesis
- brains immune cells = hyperactive in schizophrenia risk people
- animals studies = link pro-inflammatory agents and schiz symptoms
- reversed upon treatment with antipsychotics OR antibiotics that reduce microglial activation
- supports the evidence of prenatal/perinatal infection = increased schizophrenia risk
- Genome study found dopamine-receptor gene and glutamate receptor subunits = increased risk
BUT
- most significant association = chromosome 6 which includes region of genes involved in acquired immunity
MIcroglia:
healthy humans: ramifies state & survey brain for pathogens/debris –> identify = activation - change morphology
- involved in lots of homeostatic functions
- this function grows throughout lifespan
- THUS pre or perinatal primes the micrgolia –> may interact w cells in the development nervous system
- could subtly rearrange circuitry –> behavioural impairment in adolescence
describe the neurochemistry theories of schizophrenia with evidence
estrogen
- female sex hormone
- ovaries, fat, breasts and brain
- women = second peak onset of schiz at the menopuase
- estrogen protects/buffers schizophrenia
women have reduced negative symptoms, later onset, better response to antipsychotics , fewer disability/hospitalisations
- support hypothesis that sex hormones play a role
typical antipsychotics stats/symptoms
- 20-30% of patients do not respond to the drugs
- Long term use leads to symptoms that resemble Parkinson’s disease
-1/3 of the patients developed tardive dyskinesia –> cannot stop moving
atypical antipsychtoics
- Do not have Parkinson’s side effects as they have lower affinity for D2 receptors -
- Helps positive and negative symptoms rather than just positive
Clozapine - lower D2 affinity and higher other DA receptors
- use it when others fail
- reduces suicide rates too
- BAD side effects - weight gain, sedation, salivation, hypotension, etc
Parental behaviour
MOTHERS:
- a combination of hormones and experiences trigger maternal behaviour
i.e., hormones and the passage of pups through birth canal
Hormones:
- influence NOT control
- e.g. nest building is facilitated by progesterone - but continues after birth when progesterone is lower
- The Medial preoptic area (MPA) = which regulates social behaviours and social reward = crucial for maternal behaviour - lesions disrupt maternal behaviour
- The VTA-NAC pathway is involved in the reward system = also necessary –> it is activated when mothers encounter their pups
- In lactating females encountering their pups is more rewarding that cocaine (FERRIS 2005)
- Humans show activation of the reward systems when presented with pictures of their babies (BARTELS & ZEKI 2004)
PATERNAL:
- in mammals few fathers show care for offspring
- MONOGOMOUS prairie voles - share offspring care
- POLYAMOROUS meadow voles - leave the female post mating
- The size of the MPA is less sexually dimorphic in prairies voles than meadow voles
- lesions = disrupt paternal behaviour in rat and voles so it is also involved in paternal behaviour
Affiliative behaviours
- positive social behaviours within the same or different species
- neuropeptides: oxytocin and vasopressin are key for complex social behaviours (both produced in the hypothalamus)
- released as hormones from the pituitary gland
- or from axons towards specific brain regions as neurotransmitters
Affliliative behaviours
in animals
Pair Bonding in Voles
- 3-5% of mammals are monogamous
- biparental species = females and males raise their young
- voles:
- prairies voles = bond for life
- meadow voles = polyamorous - male leaves female post-mating
Exposure to partner when injected with VP vs OXT
- males and females paired for 1H
- one received administration of OXT or VP - partner preference test:
- 180 mins
- choose to enter room with stranger, with partner from earlier when they had the drug or alone
Results:
- VP and OXT increased partner preference in both females and males
–> preference is mediated by hormones
Why?
- after mating male prairie voles tended to spend significantly more time with partner than woith a stranger
- prairie vole had more VP receptors in the rewarding areas of the brain
- as well as more OXT receptors in the prefrontal cortex
- PRAIRIES GET PLEASURE OUT OF BONDING
- if we block the activation of OXT and VP
- pair preference is stopped in both sexes
- overexpression of VP receptor in the meadow voles enhanced mate preference compared to controls
how much can we generalise this ?