Addiction, Tumours and Genetic Influences Flashcards
1
Q
Reinforcement
A
- Process by which an event increases the probability of a given response
- Positive reinforcement: use drugs to feel relaxed
- Negative reinforcement: use drugs not to feel withdrawal symptoms
2
Q
Habit
A
- Impact of conditioned negative and positive reinforcement
- relapse due to stress or environmental causes
3
Q
Tolerance
A
Neuronal Changes:
- changes in receptor populations
- desensitisation of receptors
- changes in neurotransmitter vesicle content
- changes in signalling pathways
4
Q
Criteria for substance use disorder
A
- A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring with a 12 month period
- Larger amounts or over longer period
- Persistent desire or unsuccessful efforts to cut down
- Time
- Craving
- Failure to fulfil major role obligations at work, school or home
- Continued use regardless of problems (social etc)
- Physically hazardous situations eg. drink driving
5
Q
Stimulants
A
- amphetamines, cocaine, nicotine
6
Q
Depressants
A
- Heroin, alcohol
7
Q
Composite addiction cycle
A
- use/intoxication -> withdrawal -> craving
- Each stage involves discrete neuronal circuits
8
Q
Addiction Involvement
A
- All involve mesolimbic dopamine pathway, either directly or indirectly effected
- Brain areas: VTA, nucleus accumbens, prefrontal cortex, amygdala, hippocampus
- Many neurotransmitter systems
- Stress axis (CRF, CORT)
- Autonomic regulation (vagal)
- Immune system (glia, cytokines)
9
Q
Symptoms: Brain Tumour
A
- Headache (morning)
- Seizure
- Sensory deficits: vision impaired, taste, smell
- Motor deficits
- Nausea/vomiting
- Behavioural/personality changes
10
Q
Diagnosis
A
- Neurological exam
- Imaging: MRI and DWI
- Biopsy
11
Q
Grade and Prognosis
A
I - excellent - juveniile pilocyctic astrocytoma
II - variable - astrocytoma
III - poor - anaplastic astrocytoma
IV - aggressive - glioblastoma
12
Q
Types: Brain Tumour
A
- Glial: astrocytoma, oligodendroglioma, ependymoma
- Metastatic: lung, breast, melanoma, colorectal
13
Q
Astrocytoma
A
- 80% of all adult primary brain tumours
- Pilocytic astrocytoma (I) -> fibrillary astrocytoma (II) -> anaplastic astrocytoma (III) -> glioblastoma multiforme (GBM - IV)
14
Q
Pilocytic astrocytoma
A
- low grade, relatively benign
- children and young adults
- located in the cerebellum and sometimes the cerebral hemispheres
- very slow growing
- good prognosis
15
Q
Fibrillary astrocytoma
A
- Grade II
- 10-15% of astrocytic brain tumours
- Peak incidence 30-40yrs
- Mean survival 6-8 years
- Length of disease affected by rate of progression to GBM
- No current predictor of when or whether progression will occur
16
Q
Genetics: brain tumours
A
- > 60% show TP53 mutation
- > 80% in germistocytic astrocytomas
- PDGFR-a increase mRNA expression - gene amplification specific to low grade astocytomas
17
Q
Anaplastic Astrocytoma
A
- Stage III
- multinucleated cells, abnormal mitosis
- High frequency of TP53 mutations similar to diffuse astrocytomas in addiction
- Intermediate stage on the way to GBM
- Strong tendency to progress
18
Q
GBM
A
- Grade IV
- Most common adult primary neoplasm
- 45-75 yrs
- variable in appearance
- haemorrhage and necrosis present
- poor prognosis of 8-10 months
- 10% have 2 year survival rate
19
Q
Phenotype
A
- Observed genetic trait eg. chronic pain
- Functional effect of genetic changes
- Something that can be measured in a person
20
Q
Genotype
A
- Trait at gene level
- Determined by direct testing of DNA
21
Q
Central Immune System: Glia
A
- 90% of CNS cells: Microglia and astrocytes
- Immunocompetent cells: respond to different signal and mount an immune response
- Important in modulating neuronal responses:
- Pain signalling: neurological disease -> chronic pain
- Infection/sickness: neurological disease -> epilepsy
22
Q
Glial Neuronal Cross talk
A
- TLR4 (innate immune receptor) on glial cells get activated
- > release IL-1 (-> activates other glial cells to also release IL-1)
- > IL-1 activated neurones -> response
23
Q
Stages of Glial Cells
A
- Naive glia
- Priming signals: stress, drug, infection - Primed glia
- > release proinflam cytokines - Neuronal response
- Primed glia
- Activator signals: stress, infection, drugs - Activated glia: increased expression of TLR4 -> increased release of cytokines
- Increased neuronal response
24
Q
Chronic Pain
A
- Immune/non-classical component
- Glia:
- Pivotal role in generation and maintenance of enhanced pain states
- Activation of TLR, innate immune receptors
- release of inflammatory factors
25
Q
Chronic Pain: Contributing Factors
A
- Sex: females
- Environmental triggers: sleep patterns
- Genetic variability: SNPs in inflammatory factors
26
Q
Immune genetics and pain severity
A
- Worst day: no SNPs were related to pain severity
- Best day: 28% pain related to immune genetics
27
Q
Summary points for pain study
A
- Environmental factors explained a higher proportion of pain score variability in patients with FMS
- Immune genetics explained more pain score variability when patients had least amount of pain ie best day
- Genetic variability in number of genes: TGF-b and MYD88 and pain scores: support immune system involvement in pain
28
Q
Glia and epilepsy
A
- Role of TLR4 activation and glial signalling in two models of epilepsy: decreased no and frequency of seizures with TLR4 antagonist
- IL-1B expression increases after seizures: epileptic focus and frontal brain
