Lecture 10 Flashcards
Depression and Anxiety
fear
An emotional state aroused by specific external stimuli that gives rise to defensive and escape behaviours
anxiety
A generalized response to an unknown threat or internal conflict. Some argue that anxiety occurs when a person recognizes that they are not in control of the outcome of a threatening situation
anxiety disorders
Psychiatric conditions characterized by overactivity of the autonomic nervous system (fight or flight), expectation of an impending threat, and continuous vigilance for danger. (Not caused by drug intoxication or drug withdrawal)
Panic Disorder
- characterized by episodic periods of intense fear and ANS over activation (fast heartbeat, short breath, patients sincerely believe they are dying).
- Its brief and not continuous
Generalized anxiety disorder
persistent state of excessive worry and anxiety serious enough to cause a disruption in normal activities
anticipatory anxiety
a fear of having a panic attack; may lead to the development of agoraphobia.
agoraphobia
a fear of being away from home or other protected place.
○ Social interactions
Think of the lady from Grey’s who couldn’t get off the plane
social anxiety disorder
excessive fear of being exposed to the scrutiny of other people that leads to avoidance of social situations
PTSD
a reaction to a terrifying event that occurs to or is witnessed by the patient. Characterized by flashbacks, nightmares, anxiety, compulsive thoughts about event
Epidemiology of anxiety disorder
most prevalent psychiatric condition, with a lifetime prevalence of at least 20%.
○ 1/5 people will experience Anxiety Disorder in their lifetime
- Gender norms may also make it less acceptable for men to seek out a diagnosis for anxiety
- women are twice as likely as males to develop an anxiety disorder
role of genetics and gender in anxiety disorders
- Females are twice as likely as males to develop an anxiety disorder. This emphasizes the biological nature of disorder but gender may also play a role.
○ Diagnosed twice as often - Genetics does play a role in these disorders based on family and twin studies, but heritability is low compared to other psychiatric conditions (0.3).
- Few genes have been identified. For example BDNF (brain derived neurotrophic factor) may play a role in PTSD. The common variant Val66Met allele found in some humans impairs the ability to forget a fear memory in humans (and in mice)
Chronic psychological stress persistently increases
cortisol and affects neuron synapse numbers
- chronic stress is highly correlated with increased anxiety and depression
how do fMRIs work
Brain regions that are activated have increased blood flow that can be detected.
Detects changes in blood flow because the blood has iron
patients with anxiety disorders show an
over activation of the amygdala (region for fear / anger / negative emotions)
DTI (diffusion tensor imaging) can
study white matter tracts and connectivity
What do DTIs reveal about anxiety
- DTI shows reduced connectivity between frontal cortex and amygdala.
- Research focuses on the stress response, effect of chronic stress. Chronic stress increases cortisol, decreases synapse number in hippocampus and cortex
first line therapy for anxiety disorders
Selective Serotonin Reuptake inhibitors (SSRIs)
Why SSRIs over other antidepressants
Other antidepressants have also been shown to be effective.
○ SSRIs are considered to be quite safe
○ Adverse effects are not life threatening
- Benzodiazepines are used as alternate treatment for GAD and PD, but have limitations due to tolerance, withdrawal, rebound effect, abuse liability
MDD aka Unipolar Disorder characteristics
- Depressed mood most of the day.
- Diminished interest or pleasure in all or most activities.
- Significant unintentional weight loss or gain.
- Insomnia or sleeping too much.
- Agitation or psychomotor retardation noticed by others.
- Fatigue or loss of energy.
- Feelings of worthlessness or excessive guilt.
- Diminished ability to think or concentrate, or indecisiveness.
- Recurrent thoughts of death
Genetic Risk of MDD
- Genetic risk is low compared to other psychiatric brain disorders
- Heritability is 0.3-0.4 = 30-40% of risk is due to genetic factors
Environmental Risk of MDD
- Environmental risk - psychological stress
- Prevalence varies and is influenced by:
○ AGE - onset often in early adulthood but can occur anytime
○ GENDER - more females than males
○ MARITAL STATUS - divorced, widowed, single, married
§ Being divorced has a higher rate of depression than being widowed
○ EDUCATION
○ Socioeconomic Status
how does stress reduce synapses
- Chronic stress induces depression.
- Production of cortisol causes a decrease in Brain Derived Neurotrophic Factor.
- Decrease in BDNF causes a decrease in new neurons and retraction of dendrites.
8 Treatments for Depression
- Psychotherapy - cognitive behavioural therapy
- Pharmacotherapy
- Tricyclic antidepressants (TCA’s)
- Monoamine oxidase inhibitors (MAOi’s)
- Selective Serotonin Reuptake Inhibitors (SSRI’s)
- Serotonin/Norepinephrine Reuptake Inhibitors (SNRI’s)
- Hallucinogens (ketamine, psilocybin, MDMA)
- Electroconvulsive therapy (ECT & TMS) and deep brain stimulation (Helen Mayberg)
what are monoamine examples
Monoamines include dopamine (DA), norepinephrine (NE), and serotonin (5HT). Melatonin, histamine, and trace amines are also monoamines
what do monoamines regulate
mood, sleep, appetite, digestion, arousal, sexual function, cognition, reward, motivation, aggression – sometimes with opposing effects between dopamine and serotonin
monoamine transporters and the MAO enzyme are
targets for antidepressants
Phenelzine
irreversible MAOi (monoamine oxidase inhibitors)
- once it binds the enzyme it permanently inactivates it and there is no more enzyme until the cell makes more.
- Highly effective, but not used unless everything else fails because of numerous drug-drug interactions that cause hypertensive crisis (too much adrenaline) & serotonin syndrome (too much serotonin) that can be fatal.
- Hypertensive crisis (really high blood pressure) can also occur with foods that contain tyramine (cheese, wine, beer, sauerkraut).
Reversible MAOI
moclobemide
- are also effective and are much safer, but doctors are reluctant to prescribe (and pharma isn’t pushing).
Monoamine oxidase degrades
serotonin, norepinephrine, adrenaline, dopamine, tyramine
two examples of tricyclic antidepressants
chlorpromazine and imipramine
targets of TCAs
- TCAs have several targets: primary therapeutic benefit is thought to be due to blocking the reuptake of both serotonin and norepinephrine (inhibit NET and SERT).
- Antagonists for multiple serotonin receptors (5HT2A, 5HT2C, 5HT6, 5HT7) also antagonist at adrenergic receptor, histamine receptor, acetylcholine receptor.
- Also inhibits some sodium channels and calcium channels – cause of death from overdose is from cardiotoxicity – prolonged heart rhythms
adverse effects of TCAs
Histamine receptor antagonist - causes drowsiness. Anti-muscarinic cholinergic receptor - dry mouth, dry eyes
Four examples of SSRIs
- Fluoxetine – Prozac – least selective, first line for adolescents
- Paroxetine – Paxil – anti-cholinergic effects, most weight gain
- Citalopram – Celexa – most selective for SERT
- Sertraline – Zoloft – also antagonist of DAT (dopamine transporter)
Adverse effects of SSRI
Headache, Insomnia, GI disturbances (nausea, cramping, diarrhea), Sexual dysfunction (reduced libido, anorgasmia). Also weight gain, dizziness, weakness, fatigue, tremor, agitation, anxiety
- Many or most of the adverse effects diminish with continued use
discontinuation syndrome for SSRIs
anxiety, insomnia, headache, nausea. Taper off treatment by reducing dose and then taking on alternating days
what are SNRIs
The first tricyclic antidepressants actually inhibited both SERT and NET (and are more effective than SSRIs for depression)
- serotonin and norepinephrine reuptake inhibitors
SNRI Venlafaxine (Effexor), duloxetine (Cymbalta) both
block (antagonizes) both SERT and NET
SNRI Bupropion
little action at SERT, but blocks DAT and NET. So not an SSRI or a SNRI – in a class of its own
what is Serotonin Syndrome
too much synaptic serotonin
symptoms of serotonin syndrome
- Agitation or restlessness, hyper-reflexes, diarrhea, fast heartbeat and high blood pressure, hallucinations, increased body temperature, loss of coordination, nausea, vomiting
- Can be fatal –hyperthermia, tachycardia, lactic acidosis from muscle contraction
how is Serotonin Syndrome caused
- Caused by drug-drug interaction of SSRI + MAOI
○ SSRIs + dextromethorphan (cough medicine)
○ SSRIs + tryptans (migraine medicines) or some opioids (analgesics). - Serotonin syndrome can also be caused by Ecstasy (MDMA)
8 related disorders that also respond to anti-depressants
- Dysthymia – depressed mood lasting longer but less severe than MDD
- Postpartum depression – exacerbated by sudden drop in estrogen/progesterone
- Atypical depression – overeating, oversleeping, ability to react positively to positive events, oversensitivity to rejection
- Seasonal Affective Disorder – symptoms of depression – prevalent in winter – affected by amount of daylight
- Anxiety Disorders – GAD, Panic, PTSD, Social Anxiety
- Obsessive Compulsive Disorder – compulsion for repetitive activities and obsessive thoughts
- Neuropathic Pain – chronic pain & depression co-morbid
- Eating Disorders – bulimia but not anorexia nervosa
hallucinogens as antidepressants
have more rapid antidepressant effects
what are some hallucinogens that could work as anti-depressants
- Ketamine - antagonist of NMDA type of glutamate receptors - increases spine density within 1 hour of treatment. Given intravenously every 1-4 weeks.
- Psilocybin - chemical in Psilocybes “magic mushrooms” converted to psilocin in the body - agonist of 5HT2A serotonin receptor.
- LSD (lysergic acid diethylamide) - chemical derived from ergot mold - agonist of 5HT2A serotonin receptor.
- MDMA (3,4-methylenedioxymethamphetamine) - amphetamine-like drug that is selective for SERT - reverse transports serotonin.
