Depressive and Bipolar Flashcards
What is the lifetime prevalence of depressive disorders for females and males?
Females - 20 to 25%
Males - 10 to 15%
What genetic factors are associated with depressive disorders?
First degree relatives have a 2-5x increased risk of developing depression
Describe the NE hypothesis for depression.
What 2 explanations support it?
What makes this hypothesis problematic?
Reserpine was known to decrease NE and caused depression.
Amphetamines and MAOIs increase the level of NE and have anti-depressant effects.
Problems:
- only 15% on reserpine got depression
- other drugs that decrease NE don’t cause depression
- amphetamine/MAOIs increase NE in hours/days, but antidepressant effects take weeks
What is the Serotonin hypothesis for depression?
What is problematic with this hypothesis?
- initial studies showed decreased serotonin/metabolites in depression
- most antidepressants were thought to work by increasing 5HT
- substances known to deplete 5HT led to depression symptoms
Problems:
Subsequent studies showed conflicting results with increased, decreased or unchanged CNS 5HT in depressed people
Describe the stress, HPA, Hippocampus hypothesis for depressive disorders.
Stress–> cortisol secretion via HPA axis.
Glucocorticoids are essential for acute stress, but sustained excessive HPA activation can lead to mood disorders because:
Hypercortisolemia –> damages hippocampal neurons by:
- decreasing dendritic arborization [branching]
- inhibiting neurogenesis
What fraction of patients with depression have been observed to have an excessively active HPA axis and hypercortisolemia?
1/2
What is the effect of dexamethasone on depressed individuals with overactive HPA axis?
it does NOT lead to suppression of plasma cortisol.
[it should normally suppress the axis, but in depressed patients it does not]
In depressed people, the HPA axis and hypercortisolemia can be corrected with antidepressants.
What is the kindling hypothesis for depressive disorders?
What clinical evidence supports this?
Repeated exposure to stress leads to sensitization of certain areas of the brain [limbic system] so that subsequent stressors –> permanent physiologic changes.
Evidence:
- early life trauma–> later depression
- recurrent depression - stress threshold is lower for later episodes
What is the neurotrophic hypothesis for depression?
Deficiency in neurotrophic support contributes to hippocampal pathology of depression
BDNF [brain derived neurotrophic factor] is decreased in the hippocampus in depression, but can be increased with the administration of anti-depressants which also repairs some stress-induced damage to hippocampal neurons
How does the neurotrophic hypothesis help explain why anti-depressant response may be delayed?
Anti-depressants upregulate BDNF which helps:
- repair stress-induced hippocampus damage
- protect vulnerable neurons from further damage
It takes sufficient tome for levels of BDNF to gradually rise and exert neurotrophic effects.
What is the mechanism and effect of ketamine on depressive disorders?
Ketamine blocks glutamate at the NMDA-receptors.
In the hippocampus, this has been shown to:
- increase the number of dendritic spines [in mice that had prior had decreased arborization]
- reverse depressive behaviors
Unlike traditional antidepressants, ketamine works within hours, not weeks. [however, the effect lasts only about a week]
What are the 7 “depressive disorders” outlined in DSM5?
- disruptive mood dysregulation disorder [DMDD]
- major depressive disorder [MDD]
- persistent depressive disorder [PDD- dysthymia]
- premenstrual dysphoric disorder
- other specified depressive disorder [Depression NOS]
- due to Medical condition
- due to substance/medication
What are the 2 main criteria for major depressive disorder?
- one or more major depressive episode
2. no history of mania or hypomanic episodes
A major depressive episode is classified by how many symptoms occurring for what period of time?
At least 2 weeks of at least 5 of the following [one of which must be an asterisk]
- depressed mood for most of the day
- loss of pleasure and interest in life
- appetite increase or decrease
- sleep increase or decrease
- psychomotor retardation or agitation
- decreased energy/fatigue
- Guilt or worthlessness
- impaired concentration
- thoughts of death or suicide
- loss of pleasure and interest in life
[ SIGECAPS - sleep, interests, guilt, energy, conc, appetite, psychomotor, suicide]
What are the 4 other symptoms commonly seen with major depressive episodes, but not included in the DSM5?
- crying
- low libido
- hopeless, helpless
- low self-esteem
By definition, what 2 things are required to make something a true “psychiatric disorder”?
- causes impairment or distress
2. NOT substance, medication, other medical condition, or other mental disorder [usual rule-outs]
What is the criteria for persistent depressive disorder [Dysthymia]?
Depressed mood [same criteria as major depressive episode, only slightly more mild] that lasts at least 2 years.
- decreased/increased appetite
- decreased/increased sleep
- decreased energy
- low self-esteem
- problems concentrating
- hopeless
Essentially, it is chronic depression
What criteria classifies a disorder as premenstrual dysphoric disorder?
- begins in the week before menses, improves with onset of menses, minimal/absent in the weeks after menses
- at least 5 of the following:
- affective lability*
- depression*
- irritability *
- anxiety *
- decreased interests and concentration
- decreased energy
- increased appetite/food cravings
- sleep disturbances
* ** overwhelmed/out of control
* ** physical symptoms
What depressive disorder should a patient be diagnosed with if they have recurrent brief depression [less than 2 weeks], or disorders that do not meet full criteria for premenstrual dysphoric disorder, persistent depressive disorder or major depressive disorder?
Other specified depressive disorder