Module 1: L7 + L12-L17 - MDD and BIP Flashcards
What are the symptoms of depression according to ICD-10 (DK)?
- Depressive episode >/= 2 weeks
- > = 2 core symptoms (low mood, reduced pleasure/interest, reduced energy)
- > = 2 additional symptoms (reduced self esteem, self blame, thoughts about death/suicide, concentration difficulities, agitation/inhibition, sleep disturbance, appetite/weight change)
What are the symptoms of BIP according to ICD10?
- > = 2 episodes of which >=1 mania/hypomania/mixed episodes
Describe the activity of the fronto-limbic network during emotion regulation.
Top-down control: dPFC is downregulating negative emotions
Describe how the activity of the fronto-limbic network during emotion regulation is affected by unipolar depression disorder and BIP.
- Hypoactivity in dPFC
- Hyperactivity in limbic + vPFC
–> less top-down control –> emotions “take over” –> despression and/or mania
How does BIP type I and type II differ?
Type I: mania
Type II: hypomania
How does hypomania differ from mania?
Hypomania is still a functional state, whereas mania is highly dysfunctional. They differ in terms of severity and duration of:
- elevated mood/irritability
- speech, thoughts
- reduced sleep
- grandiosity
- sex drive
- reduced inhibition
What kind of bias does depressive patients show in the cognitive processing of emotional info?
Negative (enhanced fear recognition)
What kind of bias does BIP patients show in the cognitive processing of emotional info?
Positive (broader facial expression recognition impairments compared to unipolar depression)
Describe a way of screening pregnant women for the risk of postmortem depression.
Ratings of baby cries –> more negative –> predicts higher risk for PM depression
Describe the neural abnormalities of depression.
- disturbance of monoamine system
- elevated stress hormone cortisol in 50 % patients
- chronic low inflammation
- low glucose metabolism
- reduced level of neurotrophic factors incl. BDNF
–> less survival and regeneration of neurons (neural plasticity)
Describe the neural abnormalities of BIP.
- dysregulated dopamine system (D2/D3)
- elevated stress hormone cortisol
- chronic low inflammation
- reduced level of GABA transmission
- elevated monoaminergic and glutamatergic neurotransmission in mania (neurotoxic effects)
–> less survival and regeneration of neurons (neural plasticity)
Describe the structural changes in depression.
- 10 % smaller hipocampus (more reduction with longer untreated illness)
- reduced dendrite complexity
- less complex and fewer astrocytes
Describe the structural changes in BIP
- reduced hipocampus volume (not in patients treated with lithium)
Describe the monoamine hypothesis for major depression.
The hypothesis states that depression is the result of monoamine deficiency in the brain, based on experminents where inhibition of NE and 5-HT reuptake alleviated symptoms, as well as inhibition of monoamine oxidase (MAO).
Give examples of psychiatric conditions that have a high heritability.
Schizophrenia, bipolar disease,
Describe the hormonal system involved in the stress response.
HPA axis:
Hypothalamus (CRH) –> pituitary (ACTH) –> adrenal gland ==> glucocorticoids (cortisol)
Effects:
- increased blood glucose
- decreased reproductive function
- decreased immune function
Both neuronal and hormonal:
- increased fat breakdown
- increased glucose release from muscle and liver
Describe the neuronal system involved in the stress response.
Sympathetic-adreno-medullar (SAM) axis:
Central nucleus of amygdala –> CRH neurons in paraventricular nucleus of the hypothalamus –> spinal cord –> preganglionic sympathetic fibers –> adrenal gland ==> adrenaline (+NE)
Effects:
- increased HR and ventilation
- increased pupil dilation
- increased vasoconstriction in skin
- decreased digestion
Both neuronal and hormonal:
- increased fat breakdown
- increased glucose release from muscle and liver
How does glucocorticoids bind?
Glucocorticoid receptors (GRs) are intracellular receptors, so the glucocorticoids first pass the PM (lipophilic), and bind to the GR –> translocate to the nucleus –> binds to specific glucocorticoid responsive elements (GREs) on the DNA –> regulate genetranscription (or regulate genetranscription indirectly by protein-protein interactions)
Which structure supress the activation of the stress response?
The hippocampus, also contribute to negative feedback as the hippocampal structure posses GRs
What mental illnesses can chronic stress lead to?
Depreesion, anxiety and PTSD
How does stress impact neuronal plasticity?
Glucocorticoids alters plasticity in a brain region dependdent matter:
–> decreased hippocampal volume in patients with MDD and PTSD
- dendritic trees in many brain regions are altered due to stress
- in rodents: dendrites of hippocampal CA3 neurons shorten after chronic stress exposure, and neurogenesis is inhibited in the dentate gyrus
Describe the cortisolism, hypothalamic CRF release and GR sensitivity in both PTSD and MDD.
Blood cortisol levels:
PTSD: hypocortisolism
MDD: hypercortisolism
Hypothalamus CRF release:
Both: increased
GR sensitivity:
PTSD: increased sensitivity to negative feedback on HPA axis
MDD: blunted negative feedback on HPA axis
Provide examples of drugs used as first-line treatment of bipolar disorder
Benzodiazepines, e.g., Diazepam
Lithium
Antiepileptics
Provide examples of drugs used as first-line treatment of major depression.
Most common principle: inhibition of serotonin or NE reuptake:
- Selective serotonine reuptake inhibitors (SSRIs), e.g., escitalopram (lexapro, fluoxetine (prozac), sertraline (zoloft)
- tricyclic antidepressants (TCA), desipramine (NE selective)
- SNRI
- NRI
What are the major side effects of SSRIs?
- headache and nausea
- tiredness
- diarrhea
- agitation
- sleep disturbances
- sexual dysfunction
- arrythmia
- suicidal behavior and personality changes
- 5HT syndrome when overdosed in combi with e.g., TCA –> tremor, hyperthemia, cardiovascular shock
Describe the use of lithium for treatment of bipolar disorder.
- only efficient against mania in an acute attack (no acute effect on depression)
- prevents mood swings
- monovalent cation mimicking Na+: permeates Na+ channels + not pumped by the Na/K pump –> accumulaiton inside cells –> depol
- inhibtion of signaling pathways:
inhibition of inositol monophophatase –> inhibition of PI pathway –> block effects mediated by GPCRs
inhibition of glycogen synthase kinase
inhibition of cAMP production
Describe the basic principles for electroconvulsive therapy (ECT).
High dose ultra brief pulse unilaterally
What neuropsychiatric conditions are ECT used for?
- mainly for severe depression (psychotic depression)
- acute delirous conditions
- mania, schizophrenia, PD …
Describe the mechanisms of action of electroconvulsive therapy (ECT).
Resetting?
Psychological:
- changes bias to face expression
- diencephalon - HPA axis: CRH normalized after ECT
Hyperconnectivity hypothesis:
- therapeutic activity through modification of aberrant functional connectivity
Molecular: shift in sensitization of different receptors
- sensitization of 5-HT1A+3, and decreased sensitization of 5-HT2
- decreased sensitization of NE-Rbeta
How are the glutamatergic system believed to be affected in MDD?
- Decreased GABA and glutamate
- altered glu-R expression and properties in different brain regions, e.g., NR2A subunit (NMDAR) decreased in GABA interneurons in ACC
How are the immunesystem involved in MDD?
- Patients with MDD have charateristic alterations in the populations of microglia cells
- depression has been linked to increased cytokine levels
- MDD –> (typically) smaller hippocampus (high density of microglia) –> decreased microglia population
- Problems with causality: what comes first?
