8 - bipolar disorder Flashcards
what is bipolar disorder?
- bipolar disorders are a group of brain disorders that cause extreme fluctuation in a person’s mood, energy, and ability to function (DSM-5)
- causes extreme mood swings that include emotional highs (mania and hypomania) and lows (depression) that affect thought, perception, emotion, and social behaviour
- significantly reduces average life expectancy
- formally called ‘manic depression’
what are the 2 clinical subtypes of bipolar disorder?
Bipolar I Disorder
Bipolar II Disorder
describe bipolar 1 disorder
- classical bipolar disorder
- manic episodes typically alternate with depressive episodes during the course of illness (vast majority)
- there is a recurrent mania subtype (rare) (dont have depressive episodes)
describe bipolar II disorder
- NOT a milder form of BD1
- lifetime experience of at least one major depressive and one hypomanic (but not manic) episode
- often depressive episodes become predominant over time and are very functionally impairing
- hypomanic episodes do not usually cause impairment, often improve productivity at home/work, and sometimes are not disclosed because they are not seen as a problem by the patient
- usually cause of presentation is depression or unpredictability of mood
- BPII can be mistaken for recurrent MDD if you don’t look for a past history of hypomania
what is a manic episode (DSM-5)?
a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalisation is necessary)
in a manic episode, what has to be present to a significant degree and represent a noticeable change from usual behaviour?
3 or more of the following (4 if mood only irritable):
- inflated self esteem/grandiosity
- decreased need for sleep
- pressure of speech (more talkative than usually or pressure to keep talking)
- flight of ideas or subjective experience that thoughts are racing
- distractibility (ie. attention too easily drawn to unimportant or irrelevant external stimuli)
- increase in goal-directed activity (socially, work or school, sexually) or psychomotor agitation
- excessive involvement in pleasurable activities that have high potential for painful consequences (eg. unrestrained spending, sexual indiscretions, foolish business investments)
the symptoms of mania must be sufficiently severe to cause marked impairment in ____ or _____ functioning or to necessitate ______, or there are ______ features, and must not attribute to the physiological effects of a substance or to another medial condition
- social or occupational functioning
- necessitate hospitalisation
- psychotic features
what is hypomania?
- a distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days, and present most of the day, nearly every day
- at least 3 of the features that are seen in mania (or 4 if mood only irritable) must have persistent, represent a noticeable change from usual behaviour, and have been present to a significant degree
- not attributable to the physiological effects of a substance or to another medical condition
what are some difference of hypomania from mania?
- last at least 4 consecutive days unlike at least a week in mania
- hypomanic episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic
- the disturbance in mood and the change in functioning are observable by others
- the episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalisation. if there are psychotic features present, the episode, is by definition, manic
what proportion of the population has a bipolar diagnosis at any point during a 1 year period?
0.5-1%
what proportion of the population has a MDD diagnosis at any point during a 1 year period?
4-5% (5-10x higher than BD)
mean age of 1st mood episode for BP1 and BP2
BP 1 = 18 yo
BP 2 = mid 20s (a little earlier than MDD)
onset of BP in mid-late life requires what?
investigation for medical conditions such as frontal-temporal dementia, and substance ingestion or withdrawal
how much is average life expectancy reduced in BP?
reduced by 9-20 years (similar to SCZ)
what % of BP patients die by suicide? how many attempt? what is the lifetime suicide risk compared to that of the general population?
10-15%. roughly 35% will make at least one attempt
risk at least 15x higher
list some comorbid disorders common in BD?
- anxiety disorders (about 75%)
- ADHD
- impulse-control and conduct problems
- drug or alcohol abuse (roughly 60%)
- eating disorder
- metabolic syndrome
- migraine
are eating disorders more common in BP1 or 2?
BPII
name some environmental risk factors for BD
- more common in high-income countries
- adverse childhood experiences
- stress and loss eg. more common in separated, divorced, widowed individuals
- seasonal effects — mania more common in spring/summer, depression in autumn/winter
- medications
- medical disorders
what medications can increase risk of BP?
- corticosteroids
- L-DOPA
- thyroid hormones
- antidepressants can precipitate mania, esp MAOI/TCAs/SNRI
therefore antidepressants not recommended for bipolar depression, esp BP1. not as effective as in MDD
what medical conditions can increase risk of BD?
- substance misuse
- hypothyroidism ( thyroid hormone is pivotal to the creation and regulation of neurotransmitters like serotonin)
- MS
- cushing’s
- SLE (type of lupus)
- epilepsy
- CVD
- tumours
- neurosyphilis
- AIDS
- head injury
genes and BD?
- heritability >70%
- cumulative small effects of multiple risk genes
- 30 genetic risk loci now identified
> voltage-gated Ca++ and Na+ channels
GluN2A subunit of NDMA receptors
synaptic components
regulation of insulin secretion
endocannabinoid signalling
what are BPI and BPII strongly correlated with?
BPI — schizophrenia
BPII — MDD
on a manhattan plot, what does each dot represent?
a genetic variant, usually a SNP
in the loci identified, they contain genes vital for what?
- normal neuronal and synaptic function, inc for voltage gated Ca++ and Na+ channels
- subunit of the Glu NMDA receptor
- components of the synapse
In statistics you will be used to considering an association significant only if the p-value is less than _____. This is done to lower the likelihood that the association is by chance down to one in twenty. However, in GWA studies, because of the huge number of variants and individuals involved there is a very high chance that any particular association will be a _______. Because of this the significance threshold is typically elevated from ‘p is less than 0.05 or 5x10-2’ to a whopping ‘p is less than _______’. And that is the horizontal red line across the middle of the plot. Associations between particular genetic loci and the disorder or disease of interest that are above this threshold are considered _______
In statistics you will be used to considering an association significant only if the p-value is less than 0.05. This is done to lower the likelihood that the association is by chance down to one in twenty. However, in GWA studies, because of the huge number of variants and individuals involved there is a very high chance that any particular association will be a false positive. Because of this the significance threshold is typically elevated from ‘p is less than 0.05 or 5x10-2’ to a whopping ‘p is less than 5x10-8’. And that is the horizontal red line across the middle of the plot. Associations between particular genetic loci and the disorder or disease of interest that are above this threshold are considered significant
GWAS in schizophrenia — includes loci for what?
D2 receptor, glutamate neuro-transmission, synaptic plasticity, voltage-gated Ca++ channels
valproate MoA
SE of valproate in pregnancy
valproate in women of childbearing potential
