6) Depression / Bipolar Flashcards
Are depression/psychotic feature usually mood congruent or incongruent?
Congruent
Features of affective (mood) disorders: depression and bipolar disorder
- mood swings and affective modulation is normal –> BUT large overlap between normal and abnormal
depressive episode = depressed >2 weeks
manic episode = abnormally elevated >1 week
bipolar disorder = depressive episodes and at least 1 (hypo)manic episode
Depression and bipolar disorder F30-39
- frequency depression: 6.9%
- frequency bipolar disorder: 0.9%
Outdated (invalid German) triadiy system for mental disorders (could probably mostly be ignored for the exam)
1) somatically caused mental syndromes
- ‘exogene Psychosen’
a) somatic diseases with affection of the brain
- delirium, neurolues (= progressive paralysis of the insane), etc …
b) primary brain diseases
- dementia, mental retardation, encephalitis, etc …
2) mental diseases
- ‘endogene Psychosen’
- severe mental diseases with assumed somatic etiologies
–> schizophrenia, manic-depressive illness (including severe depression only)
3) Mental disorders
- ‘Abnorme Spielarten seelischen Wesens’ (abnormal predisposition of reason)
- abnormal personalities
- abnormal reactions to experiences
–> neurotic and reactive depressions, anxiety disorders, obsessive-compulsive disorders, personality and behavioural disorders, addiction
International classification of diseases (WHO): ICD
- all medical disease, injuries and causes of death
–> psychiatry just one part - predecessor: Bertillon’sche Registry of death causes (1893 Chicago, revisions every 10 years)
- 1992: ICD-10
- 1994: ICD-10 Research criteria
Diagnostics statistics and manual (APA): DSM
- for mental disorders only
- 2013: DSM-5 (over 365 diagnoses)
Mood disorders according to DSM-5 (2013): Classification
1) Bipolar disoders
a) primary
- bipolar I
- bipolar II
- cyclothymic disorder
2) Depressive disorder
a) primary
- disruptive mood dysregulation disorder
- persisent depressive disorder
- major depressive disorder
bipolar and depressive disorder
b) secondary
- prementrual dysphoric disorder
- substance/medication induced mood disorder
- mood disorder due to a medical condition
Mood disorders according to DSM-5 (2013): Specifiers
1) Severity
- mild, moderate, severe
2) Remission status
- partial, full
3) Onset
- early, late, peripartum
4) Illness pattern
- seasonal
- rapid cycling
- recurrent episode
- single episode
5) Clinical features
- anxious distress (mild, moderate, moderate-severe, severe)
- mixed features
- melancholic
- atypical
- catatonic
- psychotic (mood congruent, mood incongruent)
Biosocial and lifestyle model
Depression: graded (and treated) by severity + priority features
- not assumed causes but severity
Priority 1
- with loss of function and psychotic features
- abnormal lowering of mood, interest and vitality
Priority 2
- with loss of function
- abnormal lowering of mood, interest and vitality
Priority 3
- abnormal lowering of mood, interest and vitality
Priority 4
- ‘normal’ lowering of mood, interest and vitality
Depression: symptoms and diagnosis
- negative thinking
- reduced self-worth
- feelings of guilt
- ‘numbing’ sadness
–> no ambition
–> no happiness
–> no interest - 2/3 of all patients (range 45-95%) worldwide have somatic symptoms
–> in particular pain (neck, stomach, headache, back pain) - episode duration 8-16 weeks
- irritability and anger frequent in males, children, adolescents–> early warning sign for relapse
- cognitive dysfunction frequent (Pseudodementia in elderly)
- psychiatric co-morbidity with anxiety (disorders), addiction and others
- non-psychiatric comorbidity liek diabetes II, obesity, hypertension, ateriosclerosis, immunological disorders –> unclear what happens first and what follows
Depression: ICD-10 and DSM-5
DSM-5
- at least 5/9 symptoms
- needs to include 1) or 2)
- at least 2 weeks, nearly everyday and most of the day = change from previous functioning
1) depressed mood
2) markeldy diminished interest OR pleasure in (almost) all activities
3) weight loss OR decrease OR increase in appetite
4) insomina OR hypersomnia
5) psychomotor agitation OR retardation
6) fatigue OR loss of energy
7) feelings of worthlessness OR excessive or inappropriate guilt
8) diminished ability to think OR concentrate, or indecisiveness
9) recurrent thoughts of death, recurrent suicidal ideation, or specific suicide plan or suicide attempt
–> symptoms cause clinically significant distress or impairment in social, occupational or other areas of functioning
–> the episode is not attributed to the physiological effects of a substance or to another medical condition
ICD-10
- 5/10
- all of the above + 10) hopelessness
Depression: Course of illness
often episodic (~33%)
can be recurrent (36%)
or chronic (32%)
Community data
- impariment/disability often beyond the depressive episode
- 50% of major depressive disorders remits within 3 months
- severe or co-morbid depression average duration: 7.6 months
- the longer the episode, the lower the probability of remission
- only ~50% of those treated respond to first treatment
- 30% turn from episodic to chronic = persistent depressive disorder (>2 years)
Depression: epidemiology in EU
EU: 1-year prevalence: 6.9% (30.3Mio)
Germany: about 20% of all citizens suffer at least from 1 episode in their lifetime
- 25% of all women
- 10% of all men
- 5% of all adolescents under the age of 20
- 2% of all children under the age of 12
Only about 1/2(!) of all patients with MDD are diagnosed
- only 50% receive therapy
- 75% of all patients are untreated
Suicidality: 50% of annual worldwide suiciudes (=800.000, 10.000 in Germany)
- 15% of all (former) inpatients with recurrent MDD commit suicide
Diathesis-Stress-Model (Vulnerability-Stress-Model)
- biological factors
- family and education
- experience of loss
–> lead to increased vulnerability
- enduring stressors (chronic disease, excessive demands)
- chronic stress
- life events
–> have impact: vulnerability increases
Differential diagnosis
Psychiatric
- bipolar depression
- schizophrenia (postschizophrenic depression, schizodepressive syndrome)
- anxiety disorders
- secondary: eating disorders, AUD, somatoform disorder
- adjustment disorder
- boundary to normality: life problems
Non-psychiatric (organic depression)
- cerebrovascular (tumor, trauma, inflammation, bleeding, vascular)
- endocrine (thyriod dysfunction)
- infectious (influenza, pneumonia)
- immunological (lupus erythematodes)
- gastrointestinal (pancreatitis)
- metabolic (B12 deficiency)
- cardiovascular (COPD, caridiac insufficiency, anemia)
- medication and drugs (steroids, antihypertensive drugs, post cocaine/ecstasy)
Depression: Therapy
therapy today depends NOT on the (assumed) causes BUT on severity
- unspecific, life-style changes: activity, nutrition, stress reduction
- complimentary medicine, phytopahrmaca (eg Johanniskraut/St Johans Wort)
- psychotherapy: CBT
- specific psychotherapy for chronic depression: CBASP
- light therapy, sleep deprivation, sports
- psychedelic psychotherapy
- brainstimulation (TMS, tCDS, ECT, DBS)
NEW development
(S-)Ketamine
- either I.V (not-approved, cheap)
- nasal (approved, costly)
–> since 12/2029 for moderate to severe depression
–> since 2/2021 for acute psychiatry emergency in depression
Psychedelic supported psychotherapy
- eg psilocybin
- episode study at Charité
New TMS protocols
- intensive stimulation (everyday, 8, for 1 week)
DBS
- BUT currently evidence rather negative
Origin and cause of depression: different fields
- many theories and hypotheses about the origins of depression
- etiology = cause of a disease
- pathogenesis = origination and development of a disease
1) Dysregulated HPA-axis
2) Monamin-defecit-hypothesis
Cause of depression: Dysregulated HPA-Axis
MDD = ‘overactive’ circuit with increased cortisol and impaired negative feedback
- induced by chronic, uncontrollable stress
- Stress (physical, psychological, environmental)
- activation of hypothalamus and release of CRH
- activation of pituitary glands and release of ACTH
- adrenal glands (located above kidneys) release cortisol
- hypothalamus increases CRH if cortisol is low and decreases CRH if cortisol is high
Brain effects of cortisol
- reduced cognition
- reduced hippocamal volume
- increased psychopathology
Body effects of cortisol
- reduced heart rate variability
- increased glucose
- increased blood pressure
- increased insulin resistance
- increased visceral fat
Dysregulated HPA-Axis: Evidence and doubts
Evidence
- patients with MDD have a (moderate) elevation in cortisol
- cortisol treatment increases risk for MDD by factor 2-3 and suicide by factor 7
Doubts
- use of the dexathaxon-inhibition-test as a diagnostic test for MDD was not successful
- only 50% of all patients with MDD show a change in cortisol after effective treatment
- development of CRH antagonists as antidepressants failed
Cause of Depression: Monoamin-defecit-hypothesis
IDEA: ‘depression is like diabetes’ = a deficit in monoaminergic neuromodulators (serotonin, norepinephrine/noradrenaline, dopamine)
Evidence
- under Isoniazid (=tuberculostaticum): euphoric effects observed
- development of drugs that increase monoamine concentration at the synaptic cleft (eg tricyclic antidepressants, MAO-inhibitors)
- development of selective serotonin reuptake inhibitors (SSRI) (Prozac, had less side effects than tricyclics)
- nearly all drugs on the market show an effect on monoamone release
–> widely prescribed and advertised BUT a lot of industrial fraud
- illegal drugs –> positive effects via monoamines on mood OR induce peaceful, all-loving ‘entactogene’ feelings (ecstasy via serotonin)
–> BUT some days later rather depressed mood - Tryptophan (serotonin precursor) depleted diet can lead to depressive symptoms in susceptible individuals
Doubts
- delay between pharmacological effects (immediate increase of monoamines in synaptic cleft but anti-depressant effects after 1-2weeks)
–> receptor up and down regulation
–> intracellular signal cascades
- antidepressant drug Tianeptine enhances reuptake of serotonin
–> antidepressant effects are now postulated to be due to modulating effects on glutamate receptors
–> has effects on stress related effects on HC and PFC
–> also acts as a prtial µ-opiod receptor agonist - metadata: show that antidepressants are less effective than advertised and do not differ from placebo effects in mild and moderate MDD
–> large fight in literature, clear cases of industrial frau - good alternative: psychotherapy
–> BUT no double blind placebo controlled studies possible
Depression and ketamine
= anaesthetic drug (approved 1966) being mainly a non-competetive antagonist at the glutamate NMDA receptor
- also known as a popular party drug
- dissociative effect like ‘out-of-body-experiences’
- infusion of ketamine in MDD with an immediate antidepressant effect post-infusion (70% response) lasting 7-14 days
- intranasal S-ketamine (2x/week) approved in 2/2019 in the USA, 2019 EU, 6/2021 Germany
–> next years will show more on effectiveness, abuse potential and side effects (increase of RR, psychosis, suicidality)
KEEP IN MIND:
- at the beginning of the 20th century also opiates and cocaine were advertised as antidepressants
Bipolar disorder: Symptoms
Mania
- euphoria
- grandiosity
- logorrhea
- risky behaviour
- increased energy
- increased libido
- decreased impusle control
- decreased sleep
Psychotic symptoms
- delusions
- hallucinations
Depression/irritability
- depressed mood
- anxiety
- loss of energy
- irritability
- aggression
- suicidal ideation/behaviour
Cognitive impairment/thought disorders
- increased thought speed
- decreased attention deficits
- decreased concentration deficits
- decreased executive functions
Rapid cycling
- at least 4 mood episodes/year
- ultra rapid cycling: mood changes within day
(Hypo)manic episode (ICD-10): Mania
Mania
- elevation of mood (‘out of keeping with the patient’s circumstances)
- increased energy and activity
- pressure of speech
- decreased need for sleep
- marked distractabilty
- inflated self-esteem and grandiosity
- loss of social inhibition, inappropriate behaviour
- psychotic symptoms (in 75% of manic episodes)
(Hypo)manic episode (ICD-10): Hypomania
Hypomania
- elevation of mood (mild)
- increased energy and activity
- feeling of well-being and efficiency
- increased sociability
- increased sexual energy
- irritability
- no disruption of social relationships
- no psychotic symptoms
Bipolar disorder: subtypes
Healthy
1. Normal mood swings
- small changes around baseline
- cyclothymic personality
- larger changes around baseline
- reaching threshold of hypomania and depression (not above) - Cyclothymia
- larger changes around baseline
- occasionally reaching above threshold for depression and hypomania
Bipolar disorders
- mood instability with hypomanic and depressive symptoms ≥2 years (~30%)
- Bipolar I
- at least 1 hypomanic episode ≥4days)
- usually starts wirh depressive episode - Bipolar II
- at least 1 manic episode ≥ 1 week
- usually starts with depressive episode
Unipolar mania
- ca 5% of all BD
Bipolar disorder: Epidemiology
Lifetime prevalence = 1%
- BDI 0.6% (male = female)
- BD II 0.4% (more female)
Culturla variation:
- China 0.1%
- EU: 0.9%
–> actual difference or less diagnosed??
Onset:
- 20 years
- 5 years delay to diagnosis
- high psychiatric and non-psychiatric co-morbidity
- high rate of suicide: 1/4 to 1/2 of all patients
–> at least 1 suicide attempt: 15-20% of which are lethal
Heritability: 85%
Bipolar disorder: Neurobiology
- Gentics and environmental factors influence (each other and) epigenetic
- leads to neuronal changes which influence circuitry and brain matter
- can have systemic and behavioural consequences
—> all leading to a functional outcome
Bipolar disorder: Therapy
In acute episodes:
- mania: Lithium, valproate (antieleptic), anti-psychotics
- depression: cave antidepressants (switching), rather Lamotrigen, Quetiapin, or antidepressants + mood stabilisiers
mood stabilisers
- most have antimanic predominance OR are between similar efficacy in prevention of mania and depression
- only a few have a rather antidepressant predominance
