Stress and Mood Disorders Flashcards
What does the stress response do?
- Mobilise energy stores
- Increase blood flow to brain and muscles
- Decrease blood flow to digestive and reproductive systems
- No energy wasted on growth, reproduction, and healing
- Ignore pain
Metabolic Stress response
Insulin is suppressed but glucagon is released. This causes the release of glucose and energy
Catecholomines and glucocorticoids are also released.
Long term response is weakness and fatigue
Suppression of the HPA axis - Feedback of cortisol on the PVN
- Cortisol binds to glucocorticoid receptors
- This triggers release of endocannabinoids
- These inhibit release of glutamate from pre-synaptic terminals onto PVN
Suppression of the HPA axis - Hippocampus
- Indirect inhibition
- Contains many mineralocorticoid receptors
- Intermediate-term feedback: returns psychogenic stress response back to baseline
Pituitary Gland
Beta-endorphins is released from the pituitary gland as a hormone to suppress pain. Also releases vasopressin
Cardio-vascular stress response
Vasopressin recovers more water in the kidneys leading to an increase in blood volume.
Sympathetic nervous system causes increased heart rate and vasoconstriction, which in turn increases blood pressure.
Long term leads to coronary heart disease
Major Depression symptoms
- Depressed mood
- Sleeping problems
- Fatigue
- Change in appetite
- Lethargy
- Feelings of worthlessness
Depression and the HPA axis
Dysregulated HPA axis is common in affective disorders
Both pathological increases and decreases in cortisol can lead to depressive symptoms
Chronic stress is a major risk factor for depression
Chronic Stress
Amygdala –> HPA Axis –> cortisol
Glucocorticoids (cortisol) –> Locus Coeruleus –> noradrenergic projections –> amygdala
How do glucocorticoids damage the hippocampus?
They reduce adult hippocampal neurogenesis and shrink dendritic arbors. They also reduce glucose uptake and in the long run kill hippocampal neurons.
All this leads to smaller hippocampal volume
Other effects of chronic stress
- Depletion of noradrenaline from locus coeruleus
- Depletion of serotonin from Raphe Nuclei
- Depletion of dopamine from Ventral Tegmental Area to nucleus acumen and prefrontal cortex
Sleep in Major Depressive Disorder
Shorter REM and short sleep latency (fall asleep straight away).
Can be caused by some anti-depressants that suppress REM sleep.
Lowering mood with sleep
Phase shift between endogenous circadian rhythm and externally imposed sleep-wake cycle can lead to lower mood/depression
Depression and circadian cycle
Circadian cycle is often advanced with depressed patients. Going to sleep with circadian clock, then slowly shifting the clock may help with depression.
Bright Light Treatment
Seems to have positive effects for non-seasonal depression. Could be related to the advanced circadian clock.
Evidence of connection between melanopsin-containing RGCs and vIPOA
What mono-amine induces depression?
Reserpine (mono-amine antagonist) induces depression
Lower levels of 5-HIAA (what is made by serotonin) in cerebrospinal Fluid also induces.
Same with tryptophan.
SSRIs
Usually ingested through pills
Very lipophilic
Different pharmacokinetics for different drugs: (Prozac - slow uptake, half life of 1-4 days; Faverin - bit faster, half-life 8-28 hours; Cipramil: bit faster, half life of around 36 hours)
Negatives of SSRIs
SSRIs only work after several weeks as the first 2 weeks use an adaption of auto receptors.
In further weeks they could have the opposite effect and normalise HPA axis feedback
Adult hippocampal neurogenesis
Anti-depressants increase neurogenesis
Time course of increase = time course of effectiveness
Destroying adult neurogenesis prevents anti-depressant effects
Exercise increases adult neurogenesis and improves depression symptoms
Other uses of SSRIs
- Anxiety Disorders
- Panic Disorder
- OCD
- Eating Disorders
Ketamine
Dissociative anaesthetic and analgesic
Taken as a snorted powder, in pills, or injected
Half-life of 10-15 minutes and lasts 45 minutes
Short term effects of low doses of ketamine
Lightness and euphoria
Disconnection of thoughts and from the world
Strange perceptions
Short term effects of high doses of ketamine
Mind-body disconnect and K-holing (unresponsive to the world and having hallucinations)
Ketamine physiological action
NMDA-R Antagonist
Responsible for anaesthesia, dissociation and hallucinations, amnesia and analgesia (in the spinal cord)
Ketamine as an antidepressant
Sub-anaesthetic dose can have a profound effect on depression within hours of injection.
Typically a course of several doses per week for a few weeks
Does not last more than a few months
Why does ketamine help limit depression?
Seems to work through new synapse formation in anterior cingulate cortex
Ketamine long term effects
Memory/cognitive problems (possibly reversible)
Bladder and kidney damage (irreversible)
Abdominal cramps (k-cramps)
Ketamine physical addictiveness
Tolerance does build up
Withdrawal symptoms include psychotic features
Ketamine psychological addictiveness
Less known about it but NMDA-R antagonists can influence dopamine release in n-Acc
Anxiety disorders
A range of disorders, characterised by extreme worry, fear and chronic stress.
Often comorbid with depression and other disorders
To be a disorder it has to last more than 6 months, be inappropriate to the situation, and be debilitating
Twice as common in women than men
Treatments for anxiety
- Talking therapy like CBT
- Exposure therapies
- Drug treatments (SSRIs, beta-blockers, benzodiazepines)
Benzodiazepines: Sedatives and Anxiolytics
Usually ingested
Reach maximum blood concentration in about an hour
Lipid solubility varies from drug to drug
Depending on the exact chemical, half-life can be 90 minutes-6 days.
Benzodiazepines short term effects
Sleepiness Reduction of anxiety Anterograde amnesia Muscle relaxation Mental confusion Overdose can be lethal if taken with alcohol
Benzodiazepines Physiological Action
Facilitation of GABA-A receptors (increases inhibitory processes)
Benzodiazepines Short Term effects - Clinical use
Sleeping pills against insomnia
Anxiolytic against anxiety and panic disorders
Recovery from alcohol withdrawal
Anticonvulsant in combination with other drugs
Benzodiazepines long term effects
Mental confusion
Induction or extension of dementia
Learning problems
Can improve after medication stops
Benzodiazepines Addictiveness - Physical
Will develop even with therapeutic doses
Withdrawal symptoms include anxiety, insomnia, restlessness, agitation, and irritability
Benzodiazepines Addictiveness - Psychological
Alcoholics can be sensitive to benzodiazepine addiction as well
There are GABA-A receptors in the Ventral Tegmental area and the N Accumbens.
