4.4 - Mood disorders Flashcards
What is the lifetime (and 12-month) prevalence of bipolar-I and bipolar-II?
- bipolar I - 1.0% (0.6%)
- bipolar II - 1.1% (0.8%)
What is the lifetime rate of major depressive disorder (MDD)?
Lifetime rate of MDD is 10-20%, with studies across countries showing evidence that it is increasing with an earlier age of onset
What is the gender distribution for bipolar I, II and MDD?
- bipolar-I is F=M
- bipolar-II and MDD is F>M (in a 2:1 ratio for MDD)
What % of disability-adjusted life years (DALYs) do mental and substance abuse disorders take up?
- 7% of DALYs worldwide
- within mental and substance abuse disorders, MDD accounts for 40% and bipolar for 7% of DALYs
What are the two used disease classification systems?
- DSM-V (US manual)
- ICD (WHO manual)
What is the DSM (US manual)?
The American Psychiatric Association’s ‘Diagnostic and Statistical Manual of Mental Disorders’ - latest is DSM-V from 2013
What is the WHO manual (ICD)?
International Classification of Diseases (ICD) - latest is ICD-10 from 1994, ICD-11 currently being implemented
Until 1980, what was the Kraepelinian definition of manic depressive illness (MDI)?
- any recurrent mood episodes of any kind (depressive or manic) constituted the diagnosis of MDI
- thus MDI meant bipolar illness plus unipolar depressive illness
What are mood disorders?
- where the fundamental disturbance is a change in affect/mood to depression (with/without associated anxiety) or to elation
- the mood change is usually accompanied by a change in the overall level of activity
- most of the other symptoms are either secondary to / easily understood in the context of the change in mood and activity
What is the onset of mood disorders like?
Most of these disorders tend to be recurrent and the onset of individual episodes can often be related to stressful events or situations
What are the DSM-V criteria for depressive episodes? (8)
Occurrence of 2 weeks or more of depressed mood AND the presence of 4/8 out of the following:
- sleep alterations (insomnia / hypersomnia)
- appetite alterations (increased / decreased)
- diminished interest or anhedonia
- decreased concentration
- low energy
- guilt
- psychomotor changes (agitation or retardation)
- suicidal thoughts
When is the longitudinal diagnosis of major depressive disorder formed?
If no manic or hypomanic episodes in the past are identified, then the diagnosis of a current major depressive episode leads to a longitudinal diagnosis of MDD
What are the three subtypes of MDD according to DSM-V?
- atypical features (which represent mainly increased sleep and appetite, along with heightened mood reactivity)
- melancholic features (defined by no mood reactivity, along with marked psychomotor retardation and anhedonia)
- psychotic features (the presence of delusions/hallucinations)
What are the three core symptoms of depression?
- low mood
- anergia
- anhedonia
What are the three biological symptoms/attributes affected in depression?
- sleep
- libido
- appetite
What are the three psychological symptoms/attributes affected in depression?
- the world
- oneself
- the future
What thoughts, behaviours, feelings and physiological symptoms are present in the typical cycle of low mood?
- thoughts - “what’s the point”
- behaviours - lie in bed all day, ruminate
- feelings - low, flat, irritable
- physiological symptoms - exhaustion
What thoughts, behaviours, feelings and physiological symptoms are present in the typical cycle of high mood?
- thoughts - “I’m the best” “I can do all these things”
- behaviours - impulsive, increased activity
- feelings - elation, excitement
- physiological symptoms - increased energy, race sensitisation
What are the DSM-V criteria for manic episodes?
Euphoric or irritable mood with at least 3/7 manic criteria:
- decreased need for sleep with increased energy
- distractibility
- grandiosity or inflated self-esteem
- flight of ideas or racing thoughts
- increased talkativeness or pressured speech
- increased goal-directed activities or psychomotor agitation
- impulsive behaviour (e.g. sexual impulsivity or spending sprees)
When is type I bipolar disorder/manic episode diagnosed?
If the symptoms of a manic episode are present for minimum 1 week with notable functional impairment, a manic episode is diagnosed, leading to a DSM-V diagnosis of type I bipolar disorder
Can occur with or without previous depressive episode
When is a hypomanic episode diagnosed?
If the symptoms of a manic episode are present for minimum 4 days but without notable functional impairment, a hypomanic episode is diagnosed
When is type II bipolar disorder diagnosed?
If not a single manic episode has ever occurred, but only hypomanic episodes are present, along with at least one major depressive episode –> type II bipolar disorder
Requires previous depressive episode (unlike type I)
When is unspecified bipolar disorder diagnosed?
If manic symptoms occur for less than 4 days, or if other specific thresholds are not met for manic/hypomanic episodes
When can hypomania NOT be diagnosed?
If psychotic features are present, then hypomania cannot be diagnosed (since such features involve notable impairment by definition)
If a patient is hospitalised, what kind of manic episode is diagnosed?
If a patient is hospitalised, irrespective of duration of manic symptoms, a manic episode is diagnosed
What if manic/hypomanic episodes are caused by antidepressants?
Diagnosis of bipolar disorder still made in DSM-V (important change from DSM-IV)
Why can it be challenged whether bipolar disorders are mood disorders?
- MDD can be without sad mood
- mania can be without euphoric mood
- mood is variable and most consistent clinical features for diagnosis are psychomotor changes
What is the graph of illness course of bipolar I and bipolar II like?
- bipolar I - cycle of large mania peak followed by large depression peak
- bipolar II - cycle of small mania peak followed by large depression peak
- cyclothymia - cycle of small mania peak followed by small depression peak
What is cyclothymia?
Rare mood disorder that causes emotional ups and downs that aren’t as severe as bipolar I or II
What is rapid cycling bipolar disorder?
More than 4 cycles per year
What % of patients relapse within a year of recovery from a mood episode?
50-60%
What are patients like ‘between episodes’ in bipolar disorder?
Patients largely autonomous between episodes
What type of episode is usually first with bipolar-I patients?
- majority of first episodes are depressive (85%)
- 10% are manic episodes
- 3-5% are mixed episodes
- 90-100% of patients will develop more episodes after their first manic episode
What symptom types are present in patients with bipolar disorder?
- symptoms 47% of the time
- majority is depressive periods (33% out of 47%)
- manic/hypomanic symptoms
- cycling/mixed symptoms
How prevalent is anxiety in bipolar patients?
- 30-70% of bipolar patients
- DSM-V: “anxious distress specifier”
- worse prognosis and outcomes
How common is it for MDD patients to seek help?
- 60-70% with MDD visited a health professional in last 6mth but only 15-20% for mental health reason
- only 21% of those with a 12-month diagnosis of pure MDD received any antidepressant treatment within the same period
For which reasons were bipolar and unipolar disorders seen as different in 1970s? (5)
- bipolar illness had early age of onset (mean age 19y vs late-20s for unipolar depression)
- shorter depressive episodes (on avg <3mth in bipolar vs 6-12mth in unipolar)
- recurrent course (more frequent episodes in bipolar than unipolar, with rapid cycling in 25% of bipolar but <1% of unipolar)
- genetic specificity (manic episodes found in families of those with manic episodes but not in families of those with unipolar depression)
- differential treatment (antidepressants for unipolar depression vs neuroleptics/antipsychotics and lithium for mania)
What new evidence is there for bipolar vs unipolar not being so separate? (5)
- MDD commonly diagnosed in children, far below mean onset of late-20s
- brief depressive episodes that occur multiple times yearly are diagnosed in patients with MDD commonly (but would be rare if MDD was different to bipolar)
- genetic studies have found high rates of depressive episodes without mania in those with bipolar, and also frequent occurrence of bipolar in relatives of those with unipolar depression
- treatment now overlaps considerably, with neuroleptic agents proven effective for unipolar and bipolar depression too
- lithium has been well known to be effective not only for mania, but also for both unipolar and bipolar depression
How does heritability and insight differ in bipolar vs unipolar?
- bipolar has high heritability, unipolar (MDD) has around half heritability of bipolar
- insight is preserved in depression and impaired in mania - 50% of patients with severe mania and most with hypomania deny their symptoms
- insight has U-shaped curve in relation to severity (most impaired in hypomania and severe mania but more present in moderate states of mania)
What mood disorder diagnosis can be easily missed and be wrongly diagnosed as what?
- bipolar might be missed in patient due to lack of insight about mania/hypomania
- patient may end up with MDD diagnosis despite a history of manic episodes
- collateral Hx useful
Why is diagnosing a bipolar patient with MDD dangerous?
- might pick wrong treatment e.g. antidepressants (appear ineffective in treating acute bipolar depression)
- can also cause acute manic/hypomanic episodes
- have been shown to worsen long-term course of bipolar illness in some esp those with rapid cycling course –> more mood episodes including depressive states over time
What are attention biases in depression?
- depression is characterised by biases in maintaining/shifting attention = difficulties for depressed people to disengage from negative material
- depressed people have a prolonged maintenance of attention over negative images (e.g. people frowning) and decreased attention for positive images
- this is also seen in remitted depressed adults and those at high risk of developing depression
What are memory biases in depression?
- preferential recall of negative compared to positive material (one of most robust findings in depression literature)
- bias toward negative material or away from positive material
- memory biases also present in individuals at risk (high in neuroticism) and in recovered individuals
What are the facial expression recognition/perceptual biases in depression?
- increased recognition of negative faces and/or decreased recognition of happy faces
- emotion recognition deficits in MDD
- reduced recognition of all basic emotions except sadness
- some seen in healthy individuals at risk (high neuroticism)
What is the depressed brain’s response to simply seeing emotional face expressions?
Enhanced amygdala response to negative faces (even in absence of awareness)
What is the role of the amygdala?
- medial temporal lobe region that is involved in perception and encoding of stimuli relevant to current or chronic affective goals, ranging from rewards/punishments to facial expressions of emotion to pleasant images
- amygdala generally sensitive to detecting and triggering responses to arousing stimuli, but is biased towards detecting cues signalling potential threats (like expressions of fear)
What does an acute single dose of different antidepressants do to facial expression processing?
- noradrenergic antidepressants (reboxetine, duloxetine) - better recognition of happy faces
- serotonergic antidepressants - mirtazapine (decreased recognition of fearful faces); SSRI citalopram (mixed results - sometimes found to increase fear recognition)
What is the neurofunctional effect of an acute single dose of SSRI?
Both increased and reduced amygdala response to SSRIs
What does 7 day treatment of antidepressants do to facial expression processing?
- noradrenergic and serotonergic antidepressants - reduced recognition of anger and fear
- neurofunctional - reduced amygdala and mPFC response to fear
What is the clinical response to escitalopram (gold standard SSRI) to brain after 6 weeks of treatment?
Decrease in amygdala, thalamus, anterior cingulate and insula response to fearful faces
What does elevated baseline ACC activity in depressed patients on 1 week of SSRIs show?
Predicts positive response to treatment (i.e. decrease in depression severity following interventions)
Where are the nuclei where serotonergic neurones project from located?
In the Raphe nuclei in the midbrain where they project to all over the brain
How many different serotonin receptors are there?
14
What is the monoamine deficiency hypothesis?
Depressive symptoms arise from insufficient levels of monoamine neurotransmitters serotonin (AKA 5-HT), noradrenaline and dopamine
What is the indirect evidence for 5-HT hypofunction in depression? (9)
- 5-HT depletion by antihypertensive drug reserpine could cause depression
- clinically useful antidepressants all increase synaptic monoamine (some selectively 5-HT) concentrations
- post-mortem evidence of reduced 5-HT levels in brainstem of individuals who committed suicide
- lower levels of 5-HT1A-receptors and 5-HT4 receptors
- monoamine oxidase A increased in MDD
- blockade of serotonin synthesis by tryptophan hydroxylase inhibitor prevents antidepressant effects of both MAOIs and TCAs
- tryptophan depletion (reduced serotonin) triggers relapse in MDD successfully treated with SSRIs or CBT
- monoamine depletion correlates with decreased mood both in at risk/remission
- depression-related traits - pessimism and dysfunctional attitudes in MDD, and negativism and neuroticism in healthy, related to increased 5-HT2A receptor (decreased serotonin)
What is the best brain imaging technique to investigate brain pharmacology?
PET imaging
How does a PET scan compare to an fMRI?
- only pro - selective
- invasive
- radioactive
- expensive
- less optimal temporal and spatial resolution
How does PET imaging work?
- injection of a radioactive pharmaceutical (a ligand that is used as a tracer)
- the tracer binds to a specific target (e.g. a receptor)
What radioactive tracer can we use to measure dopamine levels?
(11C)raclopride
How can PET imaging be used to quantify dopamine receptors?
- baseline taken - tracer binds to dopamine receptors + quantification of how many receptors present is taken
- amphetamine challenge is given - amphetamine upregulates dopamine in neurones
- so much dopamine that it competes with the tracer
- new scan/measurement is taken
- subtract both scans to see the difference in the binding of the tracer, to see how much dopamine there is
How can we measure serotonin levels in the brain using PET?
- theoretically can be done with 2x PET scans
- past antagonist tracers have not been sufficiently sensitive to challenges
- can now be done using 5-HT2a agonists
What has measuring cerebral 5-HT in brains of those with and without depression shown?
- measurable 5-HT release in healthy individuals
- no measurable 5-HT release in patients with depression
- 5-HT release capacity reduced in patients with depression
How do basic tryptamine psychedelics work?
- psychedelics have their action in the brain’s serotonin system
- mimic serotonin function in the body = similar effects
What are some effects of psychadelics? (8)
- ‘oceanic boundlessness’
- spiritual experiences
- insightfulness
- blissful state
- noetic quality
- deeply felt positive mood
- transiency
- sense of duty
What are some pros of psychedelic use? (3)
- non-addictive
- low physiological and brain toxicity
- good therapeutic index
What are some cons of the safety of psychedelic use? (4)
- dysphoria
- anxiety
- nausea
- headache
What is some evidence for therapeutic value of psychedelics in treating mood disorders - what do they improve? (6)
- wellbeing
- OCD
- end-of-life distress
- addiction
- depression - long-lasting effect after single intervention
- suicidality
What are the active components in Psilocin and Ayahuasca?
- Psilocin - Psilocybin
- Ayahuasca - DMT
