Week 10: Drugs and Psychiatric Illness: Depression Flashcards
Quote showing how people can experience depression
At the end of the session, Henry described the worst depths of his depression, saying that everything could fill him with hopelessness and dread. “It could be an object,” he said, pointing at the desk. “Like that piece of paper. It bothers me in some unimaginable fashion.”
–> basically everything in life contributes to an overwhelming feeling which leads to withdrawal.
Prevalence of depression across lifespan
-Affects about 13-17% of people over the course of their lifetime (usually emerges in young adults/ late adolescence but can be influenced by other life events e.g. post-natal depression)
-Reported rates are much higher in developed areas
-Many cases are likely unreported
Is depression more common in men or women?
-Most of those who will require treatment are women
1 in 4 women
1 in 10 men
-Symptoms vary in men and women which means depression may be underdiagnosed in men because the symptoms they exhibit are not classically aligned with ideas about depression e.g. aggression.
Monoamine theory of depression: what + evidence?
-Depression caused by reduced levels of 5-HT, NE, and DA = serotonin, norepinephrine, dopamine
Support
-Depression is the most common psychiatric condition in Parkinson’s patients
-Reserpine (a drug used to treat high blood pressure) which depletes dopamine, causes depression
-Depleting 5-HT (by depleting tryptophan) produces depression
Problems with monoamine theory of depression?
-Antidepressant time lag:
Although antidepressants produce immediate physiological effects e.g. increasing levels of neurotransmitters like serotonin available at synapses, relief from depression does not occur for from 4-12 weeks
-Depleting tryptophan does not cause depression in everyone. If no history of depression, depleting tryptophan has no effect on mood
-Original monoamine theory is untenable, but monoamine function is critical to the regulation of mood
Serotonin and depression
-Decreased activity in the 5-HT system increases vulnerability to depression
-Individuals diagnosed with major depressive disorder have low levels of 5-HT in cerebrospinal fluid
-Also have low levels of tryptophan and 5-H1AA (its major metabolite) and low levels of 5-H1AA correspond with a nearly 5-fold increase in suicide risk
-Treatments that are effective in treating depression ultimately increase transmission at 5-HT synapses
-Increase in 5-HT is necessary, but not sufficient for antidepressant effects
-Autoreceptors detect increased 5-HT and inhibit release of more 5-HT: Acute administration of SSRIs does not increase 5-HT transmission. It takes several weeks for autoreceptors to habituate and for transmission at the synapse to increase. Downregulation and desensitization of autoreceptors
-Instead have enhanced functioning and sensitivity of post-synaptic 5-HT1A receptors
Glucocorticoid theory of depression + evidence
-Hypothalamic-pituitary-adrenal (HPA) axis: Controls the body’s response to stress
-Stress is the most influential environmental factor in depression so thought that if alter HPA axis activity can alter depression
-HPA axis dysfunction appears to precede onset of depression
-HPA axis normalization happens in people who get relief from depression
How are HPA and the monoamine hypothesis of depression linked?
-It’s all a circuit
-HPA axis function influences monoamine function through dopamine and 5-HT receptor function and expression
Gene x environment interactions in depression Caspi et al. (2003)
-Assessed prevalence of depression in individuals who differed in a polymorphism of the 5-HT transporter gene
-Short allele – lower transcriptional efficacy (more metabolically taxing for your brain to make serotonin transporters)
-Long allele – better transcriptional efficacy (opposite i.e. system is working more optimally)
-Changes the way the 5-HT transporter is expressed and functions
-Three groups:
s/s = two short alleles
s/l = one short, one long
l/l = two long alleles
-Measured frequency of depression/suicide as a function of stressful life events
-Found that the s/s group had the greatest increase of the depression/ anxiety measures according to number of stressful life events.
-Takeaway: there is a genetic/ environmental interaction in those who have depression.
Abuse- depression link
Three groups of participants:
-No maltreatment in childhood
-Probable maltreatment in childhood
-Severe maltreatment in childhood
See stepwise increases in probability of major depressive episode according to likelihood of abuse
SSRIS history
-Beginning in the late 1980s, SSRIs were marketed and licensed for the treatment of depression as:
Prozac
Zoloft
Paxil
Neurophysiology of antidepressants: MOAIs (1st generation)
-First generation antidepressants-MOAIs. Monoamine oxidase (MAO) breaks down monoamines (DA, NE, and 5-HT)
-MOA inhibitors block MOA activity, thus increasing synaptic activity of monoamines
-Numerous unpleasant side effects
TCAs – tricyclics - how they work + side effects
-Block monoamine transporters
Increase synaptic levels of monoamines
-Side effects:
Anticholinergics: Block muscarinic receptors
Antagonize histamine receptors
-Although generally safer than MOAIs, these side effects can be quite dangerous
Second and third generation antidepressants
-SSRIs and SNRIs/Atypicals
-Block transporters
-Increase availability at synapse
Effects of antidepressants on the body
-MAOIs adverse interactions with other drugs and food
-Tyramine – found in aged cheese, pickled herring, beer, wine, and chocolate -> Cheese effect – can’t be broken down - sweating, nausea, increased blood pressure, headaches, internal bleeding, stroke, death (why some medication labels come with food warnings)
