Affective Disorders

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What is depression?
One in ten, chance of at least one depressive episode of clinical proportions
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How many develop chronic depression?
20%
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What are the symptoms of depression?
Mood/emotional symptoms, thought/cognitive symptoms, motivational symptoms, somatic/physical symptoms
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What is bipolar depression?
Bipolar affective disorder with manic episodes, cyclothymia persistant instability of mood
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What is unipolar depression?
Mixed anxiety and depression, depressive episode, recurrent depressive, dysthymia peristant and mild
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What is increased in depression?
Metabolic activity in amygdala and orbitofrontal cortex
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Is depression inherited?
Yes to a large degree: Twin studies: McGuffin et al. 63%, Bierut et al (60)
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What is concordance rate higher for?
Bipolar depression
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Learned helplessness theory
Learned helpless animals show biological features of depression- REM sleep alterations, loss of bodyweight, diminished sexual activity elevated corticosterone.
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Linked to whay?
Cognitive function to biological function
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What is there controversy to?
Controversy is it cognitive or product of stress induced inactivity. Recovery in Seligmans after 48hrs. This recovery may be due to recovery of hypothalamic noradrenaline levels which is reduced in helpless animals
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What happens to noeadrenaline levels?
Noeadrenaline reduced shortly after exposure to inescapable shock, but recovers over the next 48 hours
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This suggests what?
Seligman's dogs did not exhibit helplessness when tested 48 hr after uncontrollable shock was because brain noradrenaline had returned to normal by this time. (Weiss et al 1975)
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Side effects of Monoamine oxidase inhibitors
Insomnia, weight gain, hypertension, drug interactions, tyramine effect
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Side effects of classic tricyclics
Sedation, anticholinergic effects, cardiovascular toxicity
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SSRI
Insomnia, Gastrointestinal disturbances, sexual dysfunction, serotonin syndrome
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Atypical anti-depressants
varies with individual mechanism of action
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Electroconvulsive shock
Memory impairment, confusion, amnesia
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Neurochemical hypotheses of depression
Depression due to depletion of monoamines esp. Noradrenaline , serotonin, dopamine originated as drugs that depleted such as reserpine neurotransmitters
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Noradrenergic hypothesis
reserpine depression is due to reduced levels of NA(noradrenaline)
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What is it supported by?
effects of antidepressants which increase NA metabolism
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The hypothesis expanded to what?
include receptor sensitivity
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By increased exposure of the receptor to what?
NA eventually the sensitivity of the receptor is decreased. B-receptors
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serotonin involved with?
Serotonin involved in pain sensitivity, emotionality and response to negative consequences
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Metabolite 5-HIAA showed what?
Reduced in cerebrospinal fluid
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What drugs were used to treat depression?
iproniazid developed in 1950’s interaction with certain foods Initially non-selective, newer selective for MAO A or B
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Drugs to treat depression
Inhibit re-uptake of noradrenaline and serotonin Effective, cheap, but dose related anticholinergic side-effects limit compliance
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What was the first stage in different anti-depressants ?
Inhibiting the enzyme monoamine oxidadase MAO that breaks down serotonin
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What happens next?
. Blocking the transporter protein for serotonin re-uptake
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How is this achieved?
This is achieved through presynaptic neurons via plasma membrane transporters. Dopamine (DAT) Serotonin (SERT) Noradrenaline (NET) These remove neurotransmitters from outside cells and recycle back into the releasing or neighbouring terminals
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What are these transporters?
targets of many psychostimulants and antidepressants, which interfere with transporter function
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Mice lacking what?
both SERT and DAT no place preference for cocaine suggesting SERT involvement in cocaine effects on reward.(Sora et al 2001)
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How do SRNR's work?
Different from tricyclics as little action on muscarinic cholinergics and histaminergic receptors (drowsy side-effects
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What was the antidepressants mechanism?
Participants rate faces for happiness. Depressed people are slower/later to rate face as happy (measured as reaction time)
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What is CRF?
major neuropeptide mediator of stress responses in the CNS
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It is expressed in what?
Paraventricular nucleus of the hypothalamus and co-ordinates the release of adrenocorticotrophin hormone (ACTH) from the anterior pituitary.
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CRF is increased in what?
CSF of depressed patients
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What is the HPA axis?
1.CRF is released in response to environmental stressor (uncertainty arousal) 2.ACTH is then released by the pituitary 3.Which in turn releases cortico-steroids 4.When stressor terminated-negative feedback occurs, shut down of the HPA axis
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Who has more glucocorticoids?
Depressed
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Elevated corticosteroids good index of stress:
elevated in times of threat 2) elevated chronically at times of loss of control
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Hwoever what?
However transient activation does not cause stress, seen following drugs such as amphetamine and novelty Excessive long term activation of HPA may induce long term damage
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Enlargment of the adrenal gland is seen in what?
patients have elevated levels of cortisol
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Antidepressants have lower what?
lower activity in the HPA axis
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Early experience can bias towards later what?
bias towards later protracted activity of the HPA (maternal separation) Corticosteroids are given for arthritis and cause depression
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Reuptake inhibitors boost what?
HPA system. Improvement in mental state associated with normalization of HPA activity
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What is cushings disease?
which involves excessive secretion of corticosteroids is commonly followed by depression
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When does neurogenesis occur?
occurs throughout life in hippocampus & olfactory bulb In rodent brain studies 9,000 new cells per day or 250,000 cells per month in adult, c. 50% go on to become neurons
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A protein that regulates what?
synaptic plasticity and neurogenesis is Brain Derived neurotrophic factor (BDNF). BDNF is reduced in depression and following chronic stress and increased by antidepressant drugs and exercise.
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What decreases neurogenesis?
Age, stress, sleep deprivation
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What increases neurogenesis?
Exercise, environmental enrichment, antidepressants
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Card 2

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How many develop chronic depression?

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20%

Card 3

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What are the symptoms of depression?

Back

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Card 4

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What is bipolar depression?

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Card 5

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What is unipolar depression?

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