1B mood disorders Flashcards
Define mood disorders
Where the fundamental disturbance is a change in affect or mood to depression (with or without anxiety) or to elation
What is mood change usually accompanied by?
Change in overall level of activity. Most of the other symptoms are either secondary to, or easily understood in the context of, the change in mood and activity.
What is the onset of mood disorder like?
Most of these disorders tend to be recurrent and onset of each episode is often related to stressful events or situations
What are the DSM-5 criteria for depressive episodes?
Occurrence of ≥2 weeks of depressed mood and presence of 4/8 of the following:
- Sleep alterations (insomnia or hypersomnia)
- Appetite alterations (increased or decreased)
- Diminished interest or anhedonia
- Low energy
- Decreased concentration
- Guilt
- Psychomotor changes (Agitation or retardation)
- Suicidal thoughts
What are the 3 core symptoms of depressive episodes?
- Low mood
- Anhedonia
- Low energy
What are the 3 biological symptoms/attributes affected in depressive episodes?
- Libido
- Sleep
- Appetite
What are the 3 psychological symptoms/attributes affected in depressive episodes?
- The world
- The future
- Oneself
Describe the typical cycle of low mood (unipolar and bipolar depression)
When is a longitudinal diagnosis of MDD formed?
If no manic or hypomanic episodes in the past are identified, then diagnosis of a current major depressive episode leads to the diagnosis
What are the 3 symptom subtypes in DSM-5 for MDD?
- Atypical features: 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 criteria for manic episodes?
Euphoria or irritable mood and 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 of pressured speech
- Increased goal-directed activities or psychomotor agitation
- Impulsive behaviour (such as sexual impulsivity or spending sprees)
What’s diagnosed if symptoms for manic episodes are present for minimum 1 week with notable functional impairment?
A manic episode is diagnosed, leading to a DSM-5 diagnosis of type I bipolar disorder
What’s diagnosed if symptoms for manic episodes are present for minimum 4 days without notable functional impairment?
A hypomanic episode is diagnosed
What if a manic episode has never occurred but only hypomanic episodes and at least 1 major depressive episode, what’s diagnosed?
DSM-5 diagnosis of type II bipolar disorder is made
What’s diagnosed if manic symptoms occur for less than 4 days or specific thresholds not met for manic or hypomanic episodes?
Unspecified bipolar disorder
What can manic episodes be characterised by?
Psychotic features (presence of delusions/ hallucinations)
If psychotic features are present, can hypomania be diagnosed?
No, since such features involve notable impairment by definition.
Similarly, if a patient is hospitalized, irrespective of duration of manic symptoms, a manic episode is diagnosed, not a hypomanic episode
What diagnosis is made if manic of hypomanic episodes are caused by antidepressants?
If manic or hypomanic episodes are caused by antidepressants, then the diagnosis of bipolar disorder is still made in DSM-5.
(an important change from DSM-IV where antidepressant- related mania/hypomania was viewed as an exclusion factor)
What is the most consistent clinical features for diagnosis of bipolar disorders?
Psychomotor changes.
Mood is variable.
What does this diagram show and what is cyclothymia?
Diagram of bipolar disorders and which out of mania and depression they count for.
Cyclothymia is a rare mood disorder that causes emotional ups and downs that aren’t as severe as bipolar I or II
What type of episode is usually first with bipolar-I patients?
The majority of first episodes are depressive:
- 85% have a depressive as first episode
- 10% a manic episode
- 3-5% mixed episode
Most (90-100%) of patients will develop more episodes after their first manic episode.
Describe the symptoms of bipolar patients
Describe a typical cycle of high mood
How prevalent is anxiety in bipolar patients?
- Very prevalent → 30-70% of bipolar patients
- It has worse prognosis and outcomes
How common is it for MDD patients to seek help?
- Low- about 70% of people with MDD visited a health professional in last 6 months but only 20% did for mental health
- Only 20% of those with a 12-month diagnosis of MDD received antidepressant treatment
For which reasons are bipolar and unipolar disorders seen as different in 70s?
- Bipolar illness has earlier age of onset (19 vs 20)
- Bipolar depressive episodes are shorter (≤3 months vs 1-12 months in unipolar)
- Bipolar episodes are more frequent than in unipolar
- Genetic specificity- manic episodes were found in families of people with manic episodes but not in families of those with unipolar depression
- Different treatments used- antidepressants for unipolar depression vs neuroleptics and lithium for bipolar
What new evidence for MDD is there?
- MDD is commonly diagnosed in children, way below mean onset of late 20s
- Brief depressive episodes occurring multiple times a year are diagnosed in MDD patients commonly whereas this would be rare if MDD was different illness from bipolar disorder
- Genetic studies found high rates of depressive episodes without mania in bipolar patients and frequent occurrence of bipolar illness in relatives of those with unipolar depression
- Treatment now overlaps considerably- neuroleptics and lithium is effective for both mania and depression both in bipolar and unipolar
How does heritability and insight differ in bi and 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
What mood disorder diagnosis can easily be 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 info often useful esp if you start doubting details in history taking- family members report manic symptoms 2x as likely as patients themselves
Why is diagnosing a bipolar patient with depression dangerous?
- Might pick wrong treatment e.g. with antidepressants which appear to be ineffective in treating acute bipolar depression
- They can also cause acute manic/hypomanic episodes
- Have been shown to worsen long term course of bipolar illness in some subjects, esp those with rapid cycling course, leading to more mood episodes including depressive states over time
What are attention biases in depression?
- Depression is characterised by biases in maintaining/shifting attention- there are difficulties for depressed people to disengage from negative material
- Depressed people have a prolonged maintenance of attention over negative pictures like frowning people and decreased attention for positive pictures
- This is also seen in remitted depressed adults and those at high risk of developing depression
Describe the memory bias in depression
- There’s preferential recall of negative compared to positive material- one of the most robust findings in depression literature
- Memory biases also present in individuals at risk of developing depression (high in neuroticism in personality traits assessment which is a sign for developing depression)
What are the facial expression perceptual biases in depression?
- There is increased recognition of negative faces and/or decreased recognition of happy faces
- There are emotion recognition deficits in MDD
- There is reduced recognition of all basic emotions except sadness
- Some of this also 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
How does fMRI work?
Detects changes in blood oxygenation and flow
What parts of the brain are involved with depression?
- There is a sustained amygdala response to negative stimuli
- The perigenual anterior cingulate cortex (ACC) appears to mediate negative attentional biases
- The lateral inferior frontal cortex is associated with impaired ability to divert attention from task-irrelevant negative info
What is the role of the amygdala?
- Medial temporal lobe region that’s involved in perception of encoding of stimuli relevant to current/chronic affective goals
- While amygdala is generally sensitive to detecting and triggering responses to arousing stimuli, it’s biased towards detecting potential threats e.g. fear expressions
What does acute single dose of different antidepressants do to facial expression processing?
- Noradrenergic antidepressants (reboxetine, duloxetine) give better recognition of happy faces
- Serotonergic antidepressants:
- Mirtazapine- decreased recognition of fearful faces
- SSRI citalopram- mixed results (sometimes found to increase fear recognition)
What does 7 day treatment of these antidepressants do to facial expression processing?
- Noradrenergic and serotonergic antidepressants give 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, ACC and insula response to fearful faces
What does elevated baseline ACC activity in depressed patients on 1 week of SSRI treatment 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
What is the monoamine deficiency hypothesis?
Depressive symptoms arise from insufficient levels of monoamine NTs in brain like serotonin (aka 5-HT), noradrenaline and dopamine
What is the indirect evidence for 5-HT hypofunction in depression?
- 5-HT depletion by antihypertensive drug reserpine could cause depression
- Monoamine depletion correlates with lower mood both in at risk and MDD in remission
- Monoamine oxidase A increased in MDD (used to break down 5-HT)
- Post-mortem evidence of reduced 5-HT levels in brainstem of individuals who committed suicide
- Clinically useful antidepressants all increase synaptic monoamine (some selectively 5-HT) concs
- Blockade of serotonin synthesis by tryptophan hydroxylase inhibitor prevents antidepressant effects of both MAOIs and TCAs
- Tryptophan depletion leads to decreased serotonin in brain and triggers relapse in MDD successfully treated with SSRIs or CBT
- Lower levels of 5-HT1A-receptors and 5-HT4-receptors in depression patients
- Depression related traits e.g. pessimism, dysfunctional attitudes, negativism- are all related to 5-HT2A-receptor increase (levels of which are inversely related to serotonin levels)
How can we try to measure serotonin in brain (it’s hard)?
- PET imaging- you inject radioactive pharmaceutical (ligand) and binds to a specific target (receptor) in brain
- Compared to fMRI it’s more selective, but it’s invasive, radioactive, expensive and with less optimal spatial and temporal resolution
How can we use serotonin measures to test dopamine receptors?
- Serotonin triggers release of dopamine
- We can do a baseline scan (give tracer that shows availability of dopamine receptors by binding to them)
- Then can do a scan after a pharmacological challenge (stress) that releases presynaptic NT e.g. amphetamine challenge that releases dopamine
- There’s so much dopamine it competes with tracer- we can subtract the 2 scans and see the difference in binding of tracer to see how much dopamine there is
Can we trace serotonin receptors?
We’ve tried- loads of tracers been tried but they haven’t been sufficiently sensitive to pharmacological challenges since they’re all antagonists
We have tried an agonist recently which is more sensitive which worked and 5-HT can be measured
It’s showed that MDD patients show reduced 5-HT release- more depressed patients also released less serotonin.
How do we measure release of cerebral 5-HT?
Using a 5HT2A agonist PET tracer
- Combine agonist radioligand 11C-CIMBI-36 and amphetamine as pharma challenge
How is cerebral 5-HT release applied to depression?
- Measurable 5HT release in healthy patients
- No measurable 5HT release in patients with depression
5HT release capacity reduced in patients with depression
How is psilocin/psilocybin administrated and how long do their affects last?
- Oral: ~4-5hrs
- IV: 1hr
How is ayahuasca administered and how long are the effects?
- Oral: ~4-5hrs
- Smoke or IV: 10-20mins
How is LSD administered and how long are the effects?
- Oral: ~10-20hrs
- IV: ~1hr
How do psychedelics work?
- Action in brain’s serotonin system
- Medications such as SSRIs also work in this system but via different mechanisms
What are the effects of psychedelics?
- Insightfulness
- Sense of unity
- Spiritual experience
- Blissful state
- Sense of sacredness/noetic quality
- Deeply felt positive mood
- Transcendence of time and space
- Ineffability
- Transiency
- Paradoxicality
Are psychedelics safe?
-Non-addictive, low physiological and brain toxicity
- Good therapeutic index
- Dysphoria/anxiety, nausea, headahce
What evidence is there for therapeutic value of full dose interventions?
Explain the recent COMPASS Phase 2b trial in TRD patients
Results demonstrated the potential for a rapid, sustained response
