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biological basis of psychological abnormality (DEPRESSION (Unipolar…
biological basis of psychological abnormality
synapses
Electrical synapse
gap junctions- 2-4mm
facing membrane have large channels that allow ions to move from one cell to the other
transmission from one neuron to the next is like action potential along an axon - VERY FAST
chemical synapse
synaptic communication mediated by the physical movement of chemicals (neurot)
gap between the axon of one neuon and dendrite of the next
small gap - larger than the electrical (20-40mm)
neuron has typically many - like 1000 synapses - slower
transmit chemical signals from one neuron to the other (presynaptic to the postsynaptic)
neurons separated by the synaptic cleft !
the connections and means of communication between nerve cells
each neuron has thousands of different synapses with other neurons
POST SYNAPTIC RECEPTORS
receptors are membrane proteins that bind to a specific transmitter - LOCK AND KEY
transmitter molecule binds to the receptor - the receptor changes shape= ion channel opens
post synaptic cleft- receptor molecules- on the post synaptic cleft specific for single neurotransmitter
receptors
ionotrophic
metabotrophic
the receptor causes a separate ion channel to open using G - proteins coupling (slow)
leads to depolarisation or hyperpolarisation of the postsynaptic membrane
neurotransmitters gate ion channels
the recognition of the neurotransmitter by the receptor controls the opening of the ion channels in one of two ways
IONOTROPHIC
ions released from the cell - NeuroT binds to the cell and then the chnnel opens and ions flow across the membrane
Control ion channel directly - when bound to the transmitter the ion chnnel opens and ions flow across the membrane- LIGAND _GATED ION CHANNELS
3) ions flow across the membrane from inside to outside the cell
2) Ion channel opens in the receptor
ESPS and ISPS spread to the axon hillock - where the axon leaves the cell body - membrane rich in gated channels
1)Neurotransmitter binds to the receptor
once ESPS reach axon hillock - net charge below the threashold (<-40mV) nothing happens if above this AN Action potential is elicited along the axon
this leads to release of NT along to next postsynaptic neuron
METABOTROPHIC
1)neurotransmitter binds to the receptor
2) G protein within the receptor is activated
3) g protein submits or intracellular messengers modulate ion channels
4) ion channel opens
5) ion flow across the membrane
BIND with the neurotransmitter but do not open the ion channel- activate g proteins that subsequently control ion channel
Neurotransmitters
amino acids
glutamate, GABA
Neuropeptides
Endorphins, enkephalin
monoamines
serotonin, Catecholomines = dopamine, adrenalin, noradrenalin
NT reuptake - continued prescence of the T in the synaptic cleft would lead to persistant ESPS or ISPS without further action potentials in the pre-synaptic neurone
avoid this nt either moved back to the presynaptic or other cells by transporters or degraded by enzymes
changes at synapses - underlie memory formation and disorders, hebbain plasticity , long term potentiation, long term depression etc.
change in receptor numbers , change in amount of transmitter release, etc
change in the structure of a synapse
change in efficacy of second messenger systems
drugs, depression and reuptake
psychoactive drugs work by binding too specific receptors in the brain - cocaine, morphine, heroine
SSRIS- treatment of depression - some types due to lack of serotonin - IE - PROZAC- work by increasing the amount of serotonin that binds to postsynaptic receptors
drugs effect synaptic transmission in many ways
increase number of AP , release Transmitters from vesicles without impulses
blocking reuptake, blocking receptors, producing more transmitter , preventing transmitter release
shown in animals:
genetic studies - IE gene 'Knockouts'
Pharmacological studies
lesion studies
measured through behavioural monitoring , neural recordings and anatomical techniques ie cell counts - neurochemistry
Genetics
play role in brain function
role varies over time - some influences apparent from birth others manifest later
environmental factors determine whether a gene becomes switched on or not
code for receptors and enzymes , NT etc
methods to studying abnormality
optogenetics- but most people with these disorders will b taking brain altering drugs
human studies- genetics
post mortem studies
structural and functional MRI
PET
DEPRESSION
Unipolar
alternating depression and normal emotional states
MZ=40%, DZ=15%
adoption studies show higher rates of depression in biological than adoptive parents
no single gene
Bipolar
fluctuation between depressive moods and euphoric, positive mood and mania
MZ=70%
DZ= 15%
geneetics
#
MOI's
inhibit enzymes which break down monoamines rasing levels at the synaptic cleft
1950's: Iproniazid, 1960s developed reserprine causing depression
SSRI's
problems with this model:
DO ANTIDEPRESSANTS REALLY WORK?
Fournier et al. (2010)
obejective was to find the relative benefit of the medication vs placebo across the initial symtptoms in severity
medication vs placebo differences varied as a function of baseline severity - superiority of medication over placebo increased with increases in baseline depression severity and crossed the threashold defined by NICE
magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or non existant in mild or moderate depression
in severe depression the benefit of medication over placebo is substantial
SSRIS increase serotonin levels in hours, relief from depression takes weeks - SSRI effect is via an intermediary response in the brain to the increased levels of serotonin
modern- Prozac, sertraline- more effective than MOAIS- fewer side effects
Tricyclic antidepressants
similar to MAOIs but different action
act to inhibit reuptake of neurot's leaving more to bind with receptors
Catecholamines
dopamine
there are normal levels of these in depressed patients
this theory ignores other important Nt like serotonin (5HT)
Noradrenaline
MOnoamine theory of depression
imaging depression:
Drevets (1998)
resting cerebral bloodflow and glucose metabolism
major depression is linked to reversiable , mood state dependant , neurophysiological abnormalities in other structures
abnormal metabolic activity is in part related to anatomical abnormalities seen in MRI studies of depression
the amygdala- is a structure which regional brain function and glucose metabolism correlate with positively with depression severity.
during drug treatment with antidepressants drug treatment that ameliorates the depressive symtoms and prevents relapse - amygdala metabolism decreases to normal.
abnormally activated amydala responses may trigger relapse and reccurrance of depressive episodes
abnormal resting metabolism in the amygdala is not linked to other conditions - specific to primary mood disorders.
single unit and lesion studies - assigning emotional significance to experimental stimuli and in organising the metabolic response
need to intergrate FMRI data with data from other sources like pet to refine understanding of anatomical correlates with depression and melancholia
Functional neuroimaging studies of depression:
studies find differences in the prefrontal cortex
bi polar depression standardly treated with Lithium - standard antid have no effect- without lithim cylcel every 14 months - with lithium every 9 years - detailed mechanism unknown - could stabalise the glutamate system
Schizophrenia
DSM IV definition:
modern approaches
Negative symptoms : social withdrawal flat effect , blunted emotional response , anhedronia , reduced motivation , poor focus on tasks and cata tonia
Positive symptoms
gained behaviour , hallucinations , delusions of grandeur
done by (andreasan (1991)
two or more of delusions, hallucinations disorganised speech , disorganised or catatonic behaviour - affective flattening - etc - must be continuous for a month perios
Brain abnormalities in patients with diagnosed schizophrenia
Grey matter loss:
Shrinkage in the cerebellar vermis, thicker corpus callosum and frontal lobe abnormalities
Thomson et al (2001) mapping adolescent brain change revels dynamic wave of accelerated gray matter loss in very early onset sxhizophrenia
Ventricular abnormalities
enlargement not related to length of illness or duration of time in hospital
Cellular disorganisation in the hippocampus in the chronic schizophrenic
most impaired individuals show the greatest disorganisation (Conrad, 1991)
Genetics : Family studies - closer related biologically the greater the chance of having a relative with schizophrenia
there are specific genes implicated in schizophrenia
Neuregluin 1: participates in glutamate, GABA and ACh receptor regulation
COMT- catecholamine production
G72: glutamatergic activtiy
Twin studies - Concordance MZ= 50% and 17% in DZ
the symptomatic twin weighs less at birth due to differentiation in the womb
more psychological distress ( affected twin has experienced different environmental factors
twins act differently due to this so receive different treatment- affected twin more sensitive and tearful
Glutamate hypothesis
NDMA receptor - postsynaptic glutamate receptor
NDMA receptor agonists- resemble + and - symptoms when induced
not one system involved
functional abnormalities
the hypoofrontality hypothesis: less activity in frontal lobes of schizophrenics
decreased activity in right middle frontal gyrus- during a context processing tsk in schizophrenic patients - Holmes et al (2005)
DEF: schizophrenics show decreased cerebral blood flow in the anterior cingulate cortex (ACC) during the performance of an auditory discrimination task (Holcomb et al, 2000)
Dorsal ACC and the PFC like the effects of ostracism on dACC ( eisenberger et al, 2003)
The dopamine Hypothesis
the dopamine hypothesis- increased d = schizo
large doses of amphetamine ( strong DA agonist ca cause psychosis with symptoms similar to schizophrenia
eatment of parkisons using L-Dopa precursor to dopamine may induce psychotic symptoms
dopamine receptor antagonists like chlorpromazine - effective antipsychotic drugs - -
bind to dopamine D2 receptors some of which associated with projections form the mesolimbic dopamine systems
studies found increase in dopamine receptors in schizophrenics including those no longer taking neuroleptic drugs
(-) TOO SIMPLISTIC
some patients show no improvement when treated with DA antagonists
Atypical neuroleptics affects many receptor types , ie serotonin and D2 receptors - more effective at relieving negative symptoms than typical neuroleptics
clozapine can also increase dopamine activity in the Frontal cortex
studies on D2 receptor levels in schizophrenics are inconistant
Synthesis of schizophrenia
genetic influences lead to 'brain abnormalitles'
Developmental influences / birth complications may exaggerate abnormalities
the emergence of schizophrenia is dependant on whether the 'damaged' brain is exposed to environmental stressors: (Rosso et al, 2000)
Panic disorder:
overwhelming fear of being about to die, general sympathetic nervous system activation
causes :green_cross:
psychological factors
general stress , life transitions
stimulants
caffeine and SSRI's
metabolic hypothesis of panic- triggers are lactate and Co2
temporal lobe abnormalities in the AMYGDALA
amydala is the fear system link in the brain
(Ziemann et al, (2009) amyggdaa is a chemosensor that reacts to changes in the body's PH produced by high levels of CO2
enhaling C02 produces fear responses in mice and the same responses produced by reducing Ph of the amydala
Hayano et al. (2009) : smaller amydala is associated with anxiety in pateients with panic dosrder
PTSD : people exposed to particularly traumatic events may show clusters of symptoms - ie intrusive memories and thought
hypervilgillance, intense physiological arousal, flashbacks triggered by innocuous stimuli
PSYCHOBIOLOGICAL MODEL of ptsd
incorporates neural mechanisms with theories of conditioning , extinction and behavioural sensitisation