Affective Disorders Flashcards
(72 cards)
1
Q
What is mood?
A
moods characterise the state of mind or inner disposition of a person; a mood is a result of prolonged feelings and colour the whole mental life while it lasts (Karl Jaspers, 1913)
2
Q
What is used to form the criteria used to classify mood disorders?
A
- using DSM and ICD-10
- the Diagnostic and Statistical Manuel for Mental Disorders
- the International Classification of Disease
3
Q
What are the four main episodes displayed in mood disorders?
A
- Major Depressive Episode
- Manic Episode
- Hypomanic Episode
- Mixed Affective Episode
4
Q
What are the Biological risk factors for depression?
A
- Genetic heritability between 17-75% - mean of 75% of people
- Physical illness
- Chronic, Severe illness, Painful, degenerative conditions, impact on mobility, impact on sexual function
- in those with Parkinson’s ⅓ of people have depression
- Stroke, Diabetes, Post-MI, Cancer
- High IQ
- Drugs
- beta-blockers
- oral contraceptive
- roaccutane
- Self-medication: marijuana, cocaine etc..
- Disrupted hormone regulation
5
Q
What are the Psychological risk factors for depression?
A
- Childhood experiences: loss of a parent/ lack of parental care, parental alcoholism/antisocial traits
- Personality traits: anxious, impulsiveness, obsessionality
- Low-self-esteem
- Chronic stress
6
Q
What are the Social risk factors for depression?
A
- Married men are less likely to have depression, whereas women are more likely to
- adverse life events - especially ‘loss events’
- Difficulty in early life/ unsafe environment at home
- Lower social economic status
- self-medication: marijuana, cocaine
7
Q
What are the Biological symptoms for depression?
A
- Diurnal mood variation - worse in the morning getting better by the evening
- Early morning wakening
- Psychomotor agitation
- Weight change/ appetite change
- Loss of libido
8
Q
What are the Psychological symptoms for depression?
A
Nihilists Perceptions
- Delusions of:
- poverty
- personal inadequacy
- guilt over presumed misdeeds, deserving of punishments and other nihilists delusions
- Hallucinations
- Auditory- defamatory or accusatory voices, cries for help
- olfactory - bad smells, rotting food
- Visual - tormentors, demons, dead bodies
- Hopelessness, Worthlessness
9
Q
What are the Core symptoms for depression?
A
- Depressed mood - present most of the day nearly everyday
- Anhedonia
- Fatigue/ loss of energy
- Disturbed Sleep
- Weight change
- Feelings of worthlessness or excessive inappropriate guilt
- Recurrent thoughts of death or suicide
10
Q
What are the Cognitive symptoms of depression?
A
- Difficulty concentration
- Poor-memory
- pseudo-dementia, sudden onset
- Fuzzy/ fullhead/ difficulty thinking
11
Q
What is classified as mild depression according to ICD-10?
A
- Presenting with 2 typical symptoms + 2 other core symptoms
12
Q
What is classified as moderate depression according to ICD-10?
A
- Presenting with 2 typical symptoms + 3 other core symptoms
13
Q
What is classified as severe depression according to ICD-10?
A
- Presenting with 3 typical symptoms + 4 other core symptoms
14
Q
How common is depression?
A
- 25% of women will have a diagnosis of depression
- 13% of men will be diagnosed with depression
- however men are more likely to complete suicide than women
15
Q
Symptoms of depression
A
- Depression of mood
- Anhedonia
- Psychomotor retardation
- Diurnal variation of mood
- Thoughts of: guilt, self-reproach, self-blame, worthlessness, depersonalization
- Agitation/ restlessness
- Anxiety/ preoccupation
- Somatic symptoms
- Hypochondriasis
- Weight loss
- Insomnia
- •Suicidal thoughts
16
Q
What is the Major Depressive Disorder criteria according to DSM V?
A
five or more symptoms during a 2 week period- must cause clinically significant distress or functional impairment: not caused by any other physiological effects
- Depressed mood most of the day, nearly every day
- Diminished interest or pleasure
- Weight loss/weight gain or appetite decrease/increase
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue or loss of energy
- Feelings of worthlessness or excessive or inappropriate guilt
- Diminished ability to think or concentrate, or indecisiveness
17
Q
What are the features of Melancholy
A
- Loss of pleasure in all, or almost all, activities
- Lack of reactivity to usually pleasurable stimuli
- Profound despondency, despair, empty mood
- Depression regularly worse in the morning
- Early-morning awakening
- Marked psychomotor agitation or retardation
- Significant anorexia or weight loss
- Excessive or inappropriate guilt
18
Q
What are the features of atypical depression?
A
- Mood reactivity
- significant weight gain or increase in appetite
- hypersomnia
- leaden paralysis
- interpersonal rejection sensitivity
19
Q
What is the management for Depression?
A
- Risk assessment and monitoring - danger to self or others
- Sleep hygiene advice
- Step 2: Mild depression/ subthreshold/ moderate → CBT, structured psychosocial activity
- Step 3: above with inadequate response to initial txt and moderate and sever depression → antidepressant SSRI + high intensity psychological intervention
- Step 4: Complex and severe depression → above with potential inpatient treatment, augment txt with antipsychotics if presenting with psychotic symptoms, consider ETC
20
Q
What is the epidemiology and impact of Major Depressive Disorder?
A
- Most common in primary care; presents more in females
- 1 in 5-lifetime prevalence for females
- males 10%
- age of onset 25-35 can be at any age
- 8-19% die by suicide
- increased morbidity/mortality from co-existing medical conditions
- decreased work productivity - it’s an immense cost to society
- suicide is the 2nd leading cause of death among 15-29 years
21
Q
What is Bipolar disorder?
A
- those who exhibit a mixed state of hypomania and subthreshold depression
22
Q
What are the clinical features of Hypomania/ hypomanic episode?
A
similar to mania, without significant disruption to work or leading to social rejection
- Mildly elevated, expansive or irritable mood
- Increased energy and activity
- Marked feelings of well-being, physical or mental efficiency
- Increased self-esteem
- Sociability
- Talkativeness
- Over-familiarity
- Increased sex drive
- Reduced need for sleep
- Difficulty focusing on one task
23
Q
What is the treatment for acute manic episodes
A
- ECT for first line txt for sever and life-threatening manic episodes
- if on anti-depressant medication → consider, reducing, stopping or swapping to alternative medication if mania is related to starting antidepressant
- if not on any medication: Antipsychotic medication as first-line
- Olanzapine
- Quetiapine
- Risperidone
- Aripiprazole
- Asenapine
- if already on antipsychotic: ensure compliance and therapeutic dose
- consider adding lithium or valproate
24
Q
What medications may induce symptoms of mania/ hypomania?
A
- Antidepressants → less seen in SSRI’s and bupropion
- Other psychotropic mediation
- BZD
- Antipsychotics - olanzapine, risperidone
- Lithium - in toxicity, and when combined with TCAs
- Anti-parkinsonian medication → amantadine, levodopa
- Cardiovascular drugs
- respiratory drugs → aminophylline salbutamol
- Anti-infection → anti-TB, clarithromycin, chloroquine
- Analgesics: buprenorphine, codeine
25
What are differentials of someone presenting with a manic episode?
* Schizophrenia, schizoaffective disorder etc. psychotic disorders
* Anxiety disorders PTSD
* Circadian rhythm disorders
* ADHD, conduct disorder
* Alcohol or drug misuse
* Physical illness
26
What are the clinical features of Mania/ Manic episode?
* **Elevated mood**
* **Increased energy,** manifests as → over-activity, pressured speech ‘flight of ideas’, racing thought, reduced need to sleep
* **Increased self-esteem** evident as → over-optimistic ideation, grandiosity, reduced social inhabitation, over-familiarity, facetiousness
* **Reduced attention/ distractibility**
* **Tendency to engage in behavior that could lead to serious consequences:** preoccupation with extravagant impractical schemes, spending recklessly, inappropriate sexual encounters
* **Marked disruption** of work, usual social activities and family life
* other behavioral manifestations: excitement, irritability, aggressiveness, suspiciousness
27
How would a Manic episode be diagnosed by DSM V?
* Abnormally and persistently elevated, expansive, or irritable mood
* For a period lasting at least one week and present most of the day, nearly every day:
* Abnormally and persistently increased activity or energy
* •3 or more of the following symptoms
* inflated self-esteem or grandiosity
* decreased for sleep
* more talkative than usual or pressure to keep talking
* flight of ideas or racing thoughts
* distractibility
* increase in goal-directed activity or psychomotor agitation
* excessive involvement in high risk activities
* The mood disturbance is sufficiently severe to cause marked functional impairment or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. The episode is not attributable to the physiological effects of a substance or to another medical condition. Can be associated to psychotic symptoms such as delusions and hallucinations
28
How would a hypomanic episode be diagnosed by DSM V?
it's the same as Mania except
* lasts at least 4 days
* the episode is not severe enough to cause marked functional impairment or to necessitate hospitalization
* unequivocal change in function that is uncharacteristic of the individual
* observable by others
29
What are the types of Bipolar disorders and what are their DSM V definitions?
* Bipolar Disorder Type I
* at least 1 manic episode
* Bipolar Disorder Type II
* one Hypermanic episode and one Depressive episode
30
Clinical features of Bipolar Disorder(s)
* anxious distress
* manic and hypomanic episodes
* depressive episodes
* psychotic features
* mixed features ?
* rapid cycling
* melancholic, atypical,
* mood congruent/incongruent psychotic features
* seasonal pattern
* others
31
What classifies as Mixed affective episodes?
* meets the full criteria for either a manic, hypomanic or depressive episode
and
* has at least 3 symptoms of the opposite polarity
32
What are features that may be associated with both mania and depression?
* Anxiety
* restlessness, tension
* worry, anticipatory anxiety, fear of losing control
* Psychotic symptoms
* Delusions and hallucinations, mood-congruent or incongruent
* Catatonia
* state of unresponsiveness that affects behaviour and motor function
33
What are the problems of early detection of Bipolar disorder?
* Mean age of onset is 21
* earlier depressive symptoms followed by later mania episodes
Best to take a probabilistic approach when diagnosing early onsets of depressive episodes
34
What would indicate that presentations of depression are Bipolar Depression?
(probable bipolarity)
* Hypersomnia
* Hyperphagia
* Atypical sx (leaden paralysis)
* Psychomotor retardation
* Psychotic features
* Mood lability; irritability
* Early onset
* Multiple episodes
* Positive family hx of BPAD
35
What would indicate unipolarity of depressive episodes?
* Initial insomnia/reduced sleep
* Appetite/weight loss
* Increased activity levels
* Somatic complaints
* Late onset
* Long episode duration
* Negative family hx of BPAD
36
What is the epidemiology and impact of Bipolar Disorder?
* Familial aggregation (10 times higher risk in 1st-degree relatives)
* Men & women affected equally (BP-I)
* Lifelong risk of recurrence | symptomatic almost half their lives
* indiscriminately affects \> 1% of the global population
* BP-II more prevalent in women
* mainly diagnosed in young adulthood - impacts the economically active population
* Highly recurrent, with a progressive course | high rate of incomplete remission | low rates of sustained recovery
* rate of suicide 20x higher than general population
37
What is the age of onset for Bipolar Disorder?
* Early onset group - 17 yrs (3 SD): 42%
* Middle onset group - 24 yrs (5 SD) : 25%
* Late onset group – 32 yrs (12 SD) : 33%
38
What is the staging of Bipolar disorder?
starting from Latent to IV
39
How are Bipolar manic, hypomanic and depressive episodes prevented in the long term?
* Lithium therapy as long-term prophylactic txt
* reduces risk of suicide, response rate of 80%, effective in patients with a ‘classical’ course of illness
* Carbamazepine
* effective in long term, response rate of 63%, more effective in bipolar spectrum than classical
* Aripiprazole
* only for continuation therapy when effective for managing acute mania
* Quetiapine
* only for continuation therapy when effective for managing acute mania or bipolar depression
* Following and episode of acute mania/ depression
* Should gradually withdraw other antipsychotic medication when therapeutic dose reached
* when euthymia reached following a depressive episode, consider tapering antidepressants after 8 weeks
40
What are other comorbidities associated with Bipolar disorder?
* linked with dementia and mild cognitive impairments
41
Give an overview of the neurobiology of Depression
* Depression of monoamine transmission
* HABA and Glutamate dysregulation
* HPA Axis and Glucocorticoids
* Neuroplasticity and Neuronal Atrophy
* Immune dysfunction
42
What neural systems are involved in depression?
* DLPFC: dorsal lateral prefrontal cortex
* VLPFC: ventral lateral prefrontal cortex
* mPFC: medial prefrontal cortex
* ACC: anterior cingulate cortex
* OFC: orbitofrontal cortex
* Amygdala
* Ventral striatum
43
What depressive symptom can Noradrenaline cause
- along with Serotonin and Dopamine
* Energy
_Serotonin:_ anxiety
_Dopamine_: Fatigue, Difficulty concentrating
_All:_ mood, sleep, psychomotor retardation, anhedonia
44
What depressive symptoms can Serotonin cause?
- along with Noradrenaline, Dopamine
* Sadness
* Suicidal ideation
* Feeling of worthlessness
* Guilt
_Noradrenaline:_ anxiety
_Dopamine:_ appetite, sexual functions, aggressiveness
_All:_ mood, sleep, psychomotor retardation, anhedonia
45
What depressive symptoms can Dopamine cause?
- along with Noradrenaline and Serotonin
* Motivation effected
* Sociability effected
_Serotonin:_ appetite, sexual functions, aggressiveness
_Noradrenaline:_ Fatigue, Difficulty concentrating
_All:_ mood, sleep, psychomotor retardation, anhedonia
46
How do most traditional antidepressants work?
* most affect the 5HT/NA systems
* MAOIs inhibit the degradation of 5HT
47
Go over the Serotonin (5-HT) and Noradrenaline (NA) pathways in the brain
* 5HT and NA have ascending and descending tracts - ascending to the cerebral cortex and limbic area and descending to the spinal cord
* 5HT cell bodies originate in the _raphe nuclei_ | NA cells originate in the _locus coeruleus_
* these project into areas that when dysregulated produce symptoms of depression
48
What is the HPA- Axis?
* Hypothalamus-Pituarity-Adrenal Axis
* used to describe the interactions between these different structures and the impact it has on mood
* control of cortisol release
49
HPA dysfunction in mood disorders
* Lack of dexamethasone suppression
* corticosteroid that prevents the release of substances in the body that cause inflammation
* the dexamethasone suppression test (DST) is used to diagnosis _Cushings Disease_
* disorder of abnormally high cortisol--\> weight gain, thinning skin, cardiac hypertrophy, poor short term memory, moon face
50
What is the effect of stress and depression on neurons in the PFC?
_Neuronal atrophy (_also in the hippocampus) in the pyramidal cells in the PFC
* decrease in apical dendrites
* decreased dendritic spine density
* decreased NMDA or AMPA receptors
* decreased Synaptic proteins
51
What role does immune dysfunction and inflammation play in the ethiopathophysiology of MDD
* evidence suggests there is a link between inflammation and depression
* there are increased inflammatory markers in depression
* elevated CRP and pro-inflammatory cytokines (IL-6, IL-1Beta, TNF-alpha)
* Translocator Protein is over-expressed on microglia and astrocytes and can be imaged using TSPO PET radioligands --\> give in vivo imaging of neuroinflammation
* Pro-inflammatory cytokines induce "sickness behaviour" that overlaps with MDD symptoms
52
Explain the relation between Hippocampal neuroinflammation and relationship to depressive symptoms in MS
* Hippocampus is frequently affected by MS demyelination
* Hippocampal volume is implicated in mood regulation and its volume is reduced in recurrent Major Depressive disorders
* It is particularly vulnerable to neuroinflammation due to very high levels of pro-inflammatory cytokine receptors
* Chronic stress and high levels of cortisol cause neuronal remodelling in the hippocampus
* Highly recurrent major depressive episodes are associated to progressive cognitive dysfunction and increased risk for subsequent onset of dementia
53
Give an overview of the treatments available for depression
* Psychotherapy
* Pharmacotherapy
* effective for Major Depression and persistent MDD
* questionable effectiveness in minor depression
* Primary care supportive counselling
54
Give an overview of 1st generation antidepressants
* **MAOi**
* *****Phenelzine, Tranylcypromine*
* nonselectively inhibit enzymes involved in the breakdown of monoamines, including 5-HT, DA and NE
* **Tricyclic antidepressants**
* *Amytryptiline, Clomipramine*
* nonselectively inhibit the reuptake of monoamines including 5-HT, DA and NE
55
Give an overview of 2nd generation antidepressants
* **SSRI: Selective serotonin reuptake inhibitors**
* *****Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine*
* **SNRI: Serotonin noradrenaline reuptake inhibitors**
* *Venlafaxine, Duloxetine*
* **alpha2 and 5-HT2c antagonist**
* *****Mirtazapine*
* **Dopamine-noradrenaline reuptake inhibitor**
* *****Bupropion _(not approved in the UK)_*
56
SSRIs Selective serotonin reuptake inhibitors as a treatment for depression
- side effects
* 2nd gen antidepressant, efficacy is equal to tryciclics in outpatients
* has a large spectrum of action
* OCD, PTSD, PAnic, GAD, social anxiety
* low toxicity and safe in overdose
* initial has to be carefully administered- slow titration (on and off)
_Side effects_
* gastro-intestinal symptoms (nausea, diarrhea)
* headache, Irritability, Anxiety
* reduction of libido and sexual dysfunction
57
Side effects of Tricyclics
* constipation,
* orthostatic hypotension,
* dry mouth,
* drowsiness,
* cardiac toxicity in overdose
58
Side effects of MAOi
* Dry mouth,
* GI side effects,
* Headache,
* Drowsiness,
* Insomnia,
* Dizziness,
* Food interactions (hypertension crises)
59
Side effects of Venlafaxine (SNRI)
* nausea,
* vertigo,
* headache,
* insomnia
60
Side effects of Mirtazapine ( alpha2 and 5-HT2c antagonist)
* drowsiness,
* sedation,
* hypotension,
* increased appetite and weight gain
61
what mitochondrial alterations are seen in Bipolar Disorder
* there are reduced mitochondrial complex I in the PFC
* altered brian mito. morphology and distribution
* reduced mRNA for genes encoding ETC components and antioxidants
* BPAD diagnosis associated with SNPs of mitochondrial genes and nuclear genes encoding STC components
* altered lactate levels in blood and CSF
* increased markers of oxidative stress
* reduced antioxidant levels
- some correlation between those with bipolar diseases and Primary mitochondrial disease
62
What are the long and short term goals when treating Bipolar Disorder?
Short term
* to reduce the severity and shorten the duration of the acute episode and achieve remission of symptoms
Long term
* prevention of new episodes and to achieve adequate inter-episode control of residual or chronic mood symptoms
63
What drugs are used to treat Bipolar Disorder?
* **Lithium:** first line for acute mania
* **Antipsychotics**
* *****Quetiapine, Lurasidone*
* *Fluoxetine/ Olanzapine combination*
* **Anticonvulsants**
* **Antidepressants**
* *****Lamotrigine + an antimanic drug*
64
How are acute manic episodes treated in Bipolar Disorder?
* DA antagonist
* *haloperidol, olanzapine, risperidone, quetiapine*
* Valproate
* Discontinue any antidepressant treatment
65
What is used in longterm treatment of Bipolar Disorder to prevent new episodes?
* Lithium (target 0.6-0.8 mmol/l)
if lithium is ineffective or not well tolerated
* Valoproate
* DA antagonist/partial agonists
* Carbamazepine
66
What is the action and effects of Lithium?
* Multiple mechanisms of actions (may need 2wks of txt to reach maximal effectiveness in manic patients)
* Multiple neurotransmitters (including DA)
* Cellular signaling
* Neurotrophic factors
* Anti-suicidal effects
* Possible efficacy on impulsive and violent behaviors
* Strongest evidence for prevention of relapses of any polarity
* _Narrow therapeutic index_
* blood tests every 3 months for the 1st year
* *Adverse long-term effects on Kidney function with excessive levels*
* *Risk of Lithium toxicity*
67
Give examples of Antipsychotics
* **D2/D3 antagonist**
* *1st generation: Haloperidol*
* **D2/D3 antagonists (also targeting 5-HT)**
* *2nd generation: Olanzapine, Risperidone, Quetiapine, Lurasidone, Asenapine, Amisulpride, Clozapine*
* **DA partial agonist**
* *Aripiprazole*
68
What are the effects of antipsychotics and when are they used?
* Rapid anti-manic effect
* Often used long-term to maintain same treatment effective in acute episode
* Long-term adverse effects on weight, glucose regulation and lipids _[except for Aripiprazole, Amisulpride, and Lurasidone]_
* Full D2 antagonism _(Haloperidol)_ may cause EPSEs
* Extrapyramidal Side Effects: movement disorders
* dystonia, akathisia, tremor, parkinsonism
69
What is the action and effect of Valproate?
* anticonvulsant
* Actions via GABA, intracellular signaling, sodium channel blockade, epigenetic modulation, etc.
* Anti-manic and effective in the prevention of mania
* may be more effective in rapid cycling mania, dysphoric mania, mixed episodes
* Useful in combination, but potential pharmacokinetic interactions
_not be used for women of childbearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development → Neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay. endocrinology disorders, limb defects and autism_
70
What is the action and effect of Lamotrigine
* anticonvulsant
* actions via GABA, Glutamate and sodium channel blockade
* Mostly effective in prevention of depressive relapses
* Ineffective as anti-manic agent
71
What is the action and effect of Carbamazepine?
* anticonvulsant
* less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective
* especially in patients who do not show the classical pattern of episodic euphoric mania
* may be better in patients with comorbid drug or alcohol problems, obesity, or women of child-bearing age
* almost exclusively effective against manic relapse
* pharmacokinetic interactions
72
What are the adverse effects of long-term pharmacological treatments for Bipolar Affective Disorder
* Weight gain (most medications, particularly Olanzapine and Quetiapine)
* Metabolic syndrome (Olanzapine, Quetiapine, Risperidone)
* Hyperprolactinemia (Dopamine antagonists)
* Tardive dyskinesia (much-reduced risk with newer agents)
* A neurological syndrome that results in involuntary and repetitive body movements
* Liver damage (e.g. Valproate)
* Kidney and Thyroid dysfunction (poorly regulated Lithium)
