mood disorders

Symptoms and features of major unipolar depression

Symptoms :

-              Low mood

-              Change in appetite

-              Sleeping problems

-              Fatigue

-              Worthlessness feeling

-              Lethargy (lack of energy)

Has to be persistent and debilitating – not easily explained by outside factors

Is depression more common in women or men

Twice as common in women than men

How does depression link with the hpa axis

Disregulated HPA axis is common in affective disorders. Can’t always say in which direction.

Pathological increases and decreases in cortisol can lead to depressive symptoms 

A big risk for depression is chronic stress. What is the positive feedback system

Positive feedback - the amygdala stimulates the HPA axis and glucocorticoids activate locus coeruleus which activates the amygdala

Chronic stress means this system is self stimulated

Locus coeruleus controls alertness  

What contributes to the positive feedback loop

The reduced negative feedback - when stress response activated for long time it reduces the negative feedback .

Repeated stimulation by glucocrticoids reduces the sensitivity of receptors in the hippocampus.

Chronically high glucocorticoids also damage hippocampal neurons, leading to a further reduction of negative feedback in long term

How are depression and sleep linked

-              Sleep latency (time taken to fall asleep shorter)

-              Rem sleep entered too early

-              Many depressed patients typically have more rem sleep and rem earlier in the night

-              Also more interrupted sleep

-              Don’t go into slow wave sleep

-              Rem sleep deprivation can help for some

-             Many anti – depressants suppress rem sleep

Which NT are especially low during rem sleep

Noradrenaline and serotonin are low during rem sleep

If deprive from rem sleep, noradrenaline and serotonin higher

Monoamine and chronic stress - which are low

Depletion of noradrenaline from locus coeruleus

Depletion of serotonin from raphe nuclei

Depletion of dopamine from ventral tegmental area to n accumbens and PFC

What is reserpine and how does it show evidence that low monoamines lead to depression

Patients taking reserpine. – prevents Monoamine from being released into synapse. (Monoamine antagonist). Was given to people to reduce blood pressure, but 15% taking this developed depression.

What is 5-HIAA and how is it evidence for low Monoamine and depression

5 – HIAA is the breakdown product of serotonin, when measured in fluid of spinal cord and brain,depressed patients have lower concentrations

Targeting monoamines - what are ssris

Anti-depressants - usually taken as pills

All very lipophilic – blood brain barrier not a problem

How do ssris work

SSRIs only work after several weeks (4-6 weeks)

They block serotonin re uptake channels

NT is in synapse for longer

Why dont SSRIs work immediately (for first couple weeks)

Due to autoreceptors for first couple weeks

How do autoreceptors work in stopping ssris from working immediately

When serotonin released, auto receptors serve a negative feedback function. When serotonin binds, it prevents cell from releasing more serotonin. Reuptake channels bring serotonin back into cell for reuse

When take ssri – we block these reuptake channels. If serotonin can’t be recycled, concentration should increase outside the cell. But because the autoreceptors detect higher serotonin levels, they prevent cell from releasing as much as usual and bring to normal levels. This lasts for about two weeks, only with repeated stimulation of the autoreceptors, they slowly adapt to higher concentration of serotonin.

Other than targeting Monoamines, what other pharmacological treatment can be used

Ketamine

What is ketamine

Ketamine is an anaesthetic and analgesic

Injected for clinical use but can also be snorted, taken in pills

Short half life of 10-15 mins – good to control

Ketamine short term effects

Disconnections

Euphoria

K-holing (hallucinating, unresponsive)

Physiological action of ketamine

Antagonist of NMDA receptors

Responsible for :

-              Anaesthesia

-              Hallucinations

-              Amnesia (NMDA receptors important part of memory formation in hippocampus)

-              Analgesia (pain circuitry in spinal cord)

Which other drug is an Nmda receptor antagonist

Alcohol – blocks Nmda receptors and increasing inhibition at gaba receptors

Ketamine as anti depressant

Been used as an anaesthetic for surgery but if give people as sub anaesthetic (lower dose that doesn’t make lose consciousness) can have strong effects of reducing depression within a few hours

Typically several doses per week for a few weeks

Doesn’t last more than a few months

Seems to work through synapse formation in anterior cingulate cortex

Long term effects of ketamine

Memory/cognitive problems – possibly reversible

Bladder and kidney damage – irreversible

Abdominal cramps

Physical addictiveness of ketamine

-              Tolerance builds up

-              Withdrawal symptoms – includes psychotic features

Psychological addictiveness of ketamine

-              Less known about this

-              NMDA – R antagonists can influence dopamine release in n Acc

Symptoms and features of anxiety disorders

Extreme worry , fears, chronic stress

Comorbid with depression

Has to last more than 6 months, debilitating to life and be inappropriate to situation

Twice as common in women

Treatments for anxiety

-              Talking therapies e.g. CBT

-              Exposure therapies

-              Drug treatments: SSRIs, beta-blockers and benzodiazepines

What do beta blockers block

Receptors for noradrenaline,

What are benzodiazepines

A group of drugs that have two effects : put you to sleep and reduce anxiety (sedatives and anxiolytics)

Usually taken as pills

About an hour for max blood concentration

Lipid soluble get through blood brain barrier

Short term effects of benzodiazepines

Sleepiness

Anterograde amnesia (make it harder to form new memories)

Muscle relaxation

Mental confusion

Physiological action of benzodiazepines

GABA agonists – they make the effect of gaba stronger. Increase inhibition caused by gaba

Examples of gaba receptors in brain - what areas benzodiazepines would effect

Cerebral cortex and hippocampus (amnesia)

Spinal cord, brainstem (muscle relaxant)

Cerebellum (muscle relaxant, anti epileptic) - good for seizures

Amygydala, orbitofrontal cortex, insula (anxiolytic)

Which other drug is a gaba – a agonist

Alcohol, can use benzodiazepines to reduce withdrawal effects of alcohol . Shouldn’t combine alcohol and sleeping pills.

Physical dependence of benzodiazepines

Will develop even with therapeutic doses

Withdrawal symptoms include maybe higher anxiety, more insomnia, agitation etc  

Psychological dependence of benzodiazepines

Alcoholics can be sensitive to benzodiazepine addiction as well

GABA a receptors in VTA and n accumbens as well