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Biological basis of Abnormality (Depression (Genetic studies: Twin studies…
Biological basis of Abnormality
revision of transmission
AP arrives at presynaptic membrane. 2. Ca2+ channels open and Ca2+ diffuses into the cell. 3. Vesicles bind with receptors and release neurotransmitter 4. Transmitter binds with postsynaptic membrane and if Na+ channel causes depolarisation and EPSP. If Cl+ channel hyperpolarization and IPSP. EPSP/IPSP progates along the neuron
Depression
Genetic
studies: Twin studies Concordance rate for general depression is around 60% MZ and 20% for DZ (Breedlove & Watson). similar % for unipolar and bipolar. Biological parents higher rates of depression than adoptive parents
Monoamine Oxidase Inhibitors (MAOI)
first in 1950's the drug reserpine (reduced catecholamine) caused depression. MAOIs inhibit enzymes that break down monoamines. Lead to Catecholamine theory of Depression (Schildkraut, 1965) - depression caused by lack of catecholamine at synapse
Tricyclic Antidepressants (TAD) similar effects to MAOI as catecholamine agonist. Inhibits reuptake of monoamines so more to bind with receptors. Supports Monamine hypothesis
found depressed patients don't have reduced levels of other catecholamines: noradrenaline and dopamine BUT
Serotonin
is important neurotransmitter -> more broadly 'Monoamine theory of depression'
Selective Serotonin Reuptake Inhibitor
s (SSRI's) most common treatment of depression. Block reuptake of serotonin at synapses. More effective than MAOI and TADs and less side effects.
Problems with SSRIs: SSRIs only take few hours to increase serotonin but takes weeks to relieve depression. 1/3 taking placebo also feel better (Berton & Nestler, 2006). Possibly a 2nd response to increased levels of serotinin mediates 5HT effect only 50% cured. 20% no improvement (Bower, 2006).
Anti-depressants do work! Fourneir et al (2010) found anti-depressant medication more helpful the more severe symptoms compared to placebo
Imaging studies: Drevets (1998) Functional neuroimaging studies of depression found Studies generally find differences in prefrontal cortex. In some brain regions abnormalities are mood-dependent (reversible) and other regions are trait like (irreversible)
Anxiety
Panic disorder
Possible causes - lack of oxygen for metabolic activity due to
high carbon dioxide
. Amygdala reacts to these changes (Ziemann, et al 2009). Mice inhailing CO2 produce fear response
Possibly caused by temporal lobe (
amygdala
) abnormalities.- smaller amygdala related to severity of panic disorder (Hayono et al (2009)
Post traumatic Stress Disorder
Psychobiological model includes both neural mechanisms and fear conditioning
PTSD sufferers have increased number of Ca2 receptors and synapses and LTP is activated so impossible to forget because of the strength of stimulus
Fear conditioning in PTSD
- NMDA is essential in LTP and synaptic plasticity so mediate learning and memory. NMDA antagonists prevent extinction in amygdala. PTSD patients may have increase NMDA which mediate fear conditioning. increased learning (i.e. associations between stimuli and trauma). Hippocampus and PFC may less effective surpress fear response.
Shin et al (2004) found more
increased amygdala
response and
decreased medial prefrontal gyrus
to
fearful
stimuli compared to happy. PTSD patients showed more change in medial prefrontal cortex than controls. Also in PTSD more change in response to fearful stimuli than happy faces.
Treatment
o Benzodiazepines – potent class of anxiolytics
Schizophrenia
Genetic studies: genes code for schizophrenia. Family studies -> parents and siblings higher risk of schizophrenic than average. Risk increases the closer the relative because share more genes (Gotteman, 1991). Adoptive studies show biological parents more likely have schizo than adoptive parents.
Twin studies: 50% of MZ twins are concordant , DZ twins only 17% (DZ no different to normal sibling). But MZ not 100% so some environmental factors protect/risk gene expression: different development in womb; different environmental factors causing stress; affected twin more sensitive
Rosso (2000) suggests genetic influences -> brain abnormalities Developmental influences/birth complications may exaggerate such abnormalities.
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Brain abnormalities : MRI scans show consistent anatomical difference in patients
Grey Matter loss
patients have less matter in cerebellar vermis, thicker corpus callosum and frontal abnormalities
Ventricular abnormalities
Larger cerebral ventricals, not due to length of illness. Enlargement predicts poorer response to drugs. Discordant twins: affected has enlarged ventricles (Torrey, 1994)
Limbic system
- discordant twin has larger hippocampus and amygdala. Post mortem- schizophrenic patients had disorganised hippocampual pyramidal cells, due to abnormal synaptic arrangement of cell inputs and outputs. More impaired = more disorganised (Conrad, 1991)
Functional abnormalities
Hypofrontality Hypothesis
- less activity in frontal lobes in schizophrenia
Decreased activity in middle frontal gyrus during context processing task (Holmes, 2005).
Hypofrontality = decreased cerebral blood flow in ACC during auditory discrimination task (Holcomb et al 2000)
Differences in Brain activation (Breedlove & Watson) - frontal cortex impaired in schizo, impaired performance on tests involving frontal cortex. PET scans less activity in frontal than posterior lobes. Neurons in frontal cortex have less dense spines
Treatment
Dopamine Hypothesis
- pps with schizo have excess dopamine release of receptors
Neuroleptics- drugs reduce symptoms and block postsynaptic dopamine receptors
Drug abuse evidence- amphetamine (Dopamine agonist) cause psychosis similar to schizo . Amphetamine prolongs release of dopamine and prolongs action by blocking reuptake
Studies found increased dopamine receptors even when no longer taking neuroleptics
Dopamine receptor antagonists (chlorprozamine ) effect treatment but not everyone
Glutamate Hypothesis -
schizophrenia result under activation of glutamate receptors
Evidence NMDA receptor antagonists (PCP) produce positive and negative schizo-like symptoms in monkeys. Can't see effect of increasing glutamate activity as NMDA receptor antagonists cause seizures. Evidence of Glutamate receptor agonist improves positive and negative symptoms in schizo
changes at the synapse
everything we learn and memory and disorders due to Hebbian Plasictity, LTP and LTD
change in number of receptors, structure of synapse and efficacy of 2nd messenger can all lead to abnormality/
Neurotransmitter reuptake. IF neurotransmitter remains in cleft persistently causes EPSPs /IPSPs without more APs.
either reuptaked by presyamnptic membrane by transporters.
Or destroyed by enzymes
Drugs affect synapses
Increasing number of action potentials
Release transmitters from vesicles without impulses
Blocking re-uptake
Blocking receptorsProducing more transmitter
Preventing transmitter release
Psychoactive drugs (cocaine) bind to specific receptors in brain
Methods of studying abnormality
Genes are important in brain function. if something (enzyme/receptor) is incorrectly coded it will be expressed in behaviour
Human studies: twin studies, fMRI , PET, post-mortem studies