MDD Flashcards by Maglinte, Frezha Mae O.

Most common mood disorder

Depression

How well did you know this?

Not at all

Perfectly

Classified as a unipolar mood disorder

Major depression

How well did you know this?

Not at all

Perfectly

Classified as when an emotional state, such as sadness, becomes chronic and uncontrollable.

Major depression

How well did you know this?

Not at all

Perfectly

Have an unclear nature of how they occur due to the difficult availabilty of human brain tissue for neurochemical measurement until patients are post-mortem.

Mood disorders

How well did you know this?

Not at all

Perfectly

Range of greater prevalence of women than men with regards to epidemiology of MDD according to age in adolescence - mid 50’s

1.7 - 2.7 times

How well did you know this?

Not at all

Perfectly

In 65-80 y.o. people, what percentage does MDD occur in men and women?

Men : 9.6%
Women: 20.4 %

How well did you know this?

Not at all

Perfectly

Other prevalence of MDD

Comorbid substance abuse
Suicide attempts
Death occuring frequently

How well did you know this?

Not at all

Perfectly

Hereditary epidemiology degree of liability

37% hereditary liability wherein 8-18% with MDD have atleast a degree relative with a history of depression

How well did you know this?

Not at all

Perfectly

Environmental epidemiology percentsage

63% of the variance in liability was due to an individual-specific environment.

How well did you know this?

Not at all

Perfectly

Epigenetic factors of MDD

Genome
Environment

How well did you know this?

Not at all

Perfectly

2-3 times increase in lifetime risk of developing MDD among first degree relatives with 37% heritability

Genome factor

How well did you know this?

Not at all

Perfectly

2 types of environmental factor in the epigenetic mechanism of MDD which are 63%

Aversive
Protective

How well did you know this?

Not at all

Perfectly

Aversive factors

Prenatal factors
Childhood trauma
Stress
Medical illness
Drug abuse

How well did you know this?

Not at all

Perfectly

Protective

Social support
Coping
Exercise

How well did you know this?

Not at all

Perfectly

MDD equation

Genome + environment = MDD

How well did you know this?

Not at all

Perfectly

Clinical presentations of mdd

Affective symptoms
Cognitive symptoms
Somatic - vegetative symptoms

How well did you know this?

Not at all

Perfectly

Pathophysiology of MDD

Brain network level
- regional brain volumes
- cognitive control circuit

Molecular level
- neurotransmission
- neuropasticity
- stress hormones
- inflammation

How well did you know this?

Not at all

Perfectly

Symptoms reported by MDD patients consistently reflect changes in which transmitters?

Brain monoamine neurotransmitters (NTs)

How well did you know this?

Not at all

Perfectly

Symptoms reported by MDD patients consistently reflect changes in which transmitters?

Brain monoamine neurotransmitters (NTs)

How well did you know this?

Not at all

Perfectly

Decreased levels of these amines are typically present in the brains of depressed patients.

5-HT, DA, NE

How well did you know this?

Not at all

Perfectly

Hypothesis where decreased levels and functional deficiencies of 5-HT, DA, and NE, are typically present in the brains of depressed patients.

Monoamine hypothesis (Biogenic Amine Hypothesis)

How well did you know this?

Not at all

Perfectly

Primary Hypotheses for the development of MDD

Monoamine Hypothesis
Neural Plasticity Hypothesis
Neuroinflammatory hypothesis
Hypothalamic-pituitary-adrenal (HPA) axis

How well did you know this?

Not at all

Perfectly

Regulates neuronal plasticity

Brain-derived neurotrophic factor

How well did you know this?

Not at all

Perfectly

Might impact the development of synaptic structures, such as axons and dendrites, and their growth and remodeling.
might enhance the long-term synaptic transmission function of the hippocampus through pre- and post-synaptic pathways

Brain-derived neurotrophic factor (BDNF)

How well did you know this?

Not at all

Perfectly

pathogenesis of depression is significantly influenced by what?

neuroplasticity and remodeling

An inflammation-related disease that worsens as inflammation increases and progresses.

Depression

glial cell activation in the brains of depressed patients results in the release of what

pro-inflammatory cytokines

examples of pro-inflammatory cytokines

Interleukin-6 (IL-6) Interleukin 1 beta (IL-1B) TNF-alpha

pro-inflammatory cytokines can lead to what

neuroinflammation and neuronal death

glial cells also produce what substances?

Nitric oxide synthase Cyclooxygenase-2 (COX-2)

emerged as a novel target for the treatment of depression

Neuroinflammation

HPA dysfunction in Px with depression have high _?

Glucocorticoid levels

Primary function of the HPA axis

regulate the stress response

hormone released by hypothalamus when we are stressed

corticotropin-releasing hormone (CRH)

Signals the pituitary gland to secrete a hormone called adrenocorticotropic hormone into the bloodstream

Corticotropin-releasing hormone

Site where the ACTH travels down and prompts the release of a hormone called cortisol from the cortex, or outer layer, of the adrenal glands

Adrenal glands

helps mobilize energy like glucose so the body has enough power to cope with prolonged stressor

Cortisol

senses high levels of cortisol in the blood

receptors in areas of brain like hypothalamus and hippocampus

mechanisms involved when cortisol levels in the blood are high

negative feedback mechanism which shuts off the stress response

Neurotransmitters

1. Glutamate 2. GABA 3. Dopamine 4. Adrenaline 5. Serotonin 6. Oxytocin 7. Acetylcholine

main excitatory neurotransmitter in the CNS

Glutamate

main inhibitory neurotransmitter reduces the activity of the CNS blocks certain signals from the brain

GABA

most thrilling neurotransmitter plays a major role in the brain's reward system proved critical to CNS functions such as movement, pleasure, attention, mood, and motivation

Dopamine

responsible for body's fight or flight response body's defense mechanisms against stress

Adrenaline (epinephrine)

promotes satisfaction after eating and keeps appetite in check

Serotonin

love hormone

Oxytocin

two main actions of oxytocin in the body

1. contraction of the womb during childbirth 2. Lactation

directly affects muscles. triggers an action potential or command in the muscle fiber. makes muscle contract instead of sending signals to a brain cell

Acetylcholine

A deficit in the concentration of the brain's NE, Dopamine, and/or serotonin resulting in depression

Neurochemical dysregulation

Antidepressant therapies focus on what ?

Increasing monoamine neurotransmitter levels within the synapses

Lipid soluble and can penetrate the BBB. Binds and inhibits the catecholamine pump on the storage vesicles in central and peripheral adrenergic neurons

Reserpine

Inhibits uptake of norepinephrine, dopamine, and serotonin into presynaptic storage vesicles

Reserpine

reserpine in combination with these may have additive orthostatic hypotensive effects when used with beta-blockers due to catecholamine depletion.

Beta-blockers

may also interfere with reflex tachycardia, worsening the orthostasis

Beta-blockers

cause of secretion of pro-inflammatory cytokines which causes immunosuppression and inflammation

Chronic cortisol release in the body

results to neuronal atrophy of the hippocampus resulting in no cell growth consequently causing a reduction of the hippocampal brain-derived neurotrophic factor (BDNF)

Neuroendocrine dysregulation

Depressed individual's post-mortem brains have shown a widespread decrease in what neurotransmitter receptor subtype??

serotonin or 5HT-1a receptor subtype

where does the 5 HT-1a receptor subtype bind?

Frontal. temporal, and limbic cortex

what is found in the frontal cortex of some suicide victims with depression?

NE receptor alterations

Alterations in NE systems may be linked to what?

Attention or concentration difficulties as well as sleep and arousal disturbances in depression

T/F: depressed individuals have also been found to have abnormalities in cerebral blood flow and glucose metabolism

Duration of symptoms to be present for diagnosis

2 weeks

feelings most commonly seen

sadness and despair irritability and hopelessness

symptoms

1. depressed or irritable mood 2. loss of interests and pleasures - includes interpersonal relationships 3. significant weight gain or loss (5%0 in a month 4. sleep disturbances: insomnia/hypersomnia 5. psychomotor agitation or retardation: restlessness or agitation 6. fatigue or loss of energy 7. feelings of worthlessness or exccessive guilt: pessimistic/negative outcomes are perceived 8. poor concentration or indecisiveness 9. resent thoughts of suicide/death

Affective symptoms of depression

feeling of sadness loss of interest normally pleasurable activities change in appetite and sleep loss of energy problems with concentration and decision-making

cognitive symptoms

difficulty remembering, diff. speaking diff. understanding problems of concentrations loss of motivation

somatic-vegetative

digestive issues heart palpitations or arrythmias shortness of breath or trouble breathing NV Change in body temperature

main objective of Tx

complete remission of depression with full functional recovery and the development of resilience

Examples of psychological therapy

1. cognitive behavioral therapy 2. interpersonal therapy 3. acceptance and commitment therapy 4. mindfulness-based cognitive therapy

First line pharmacotherapy

- SSRIs, NaSSAs, NDRIs, SNRIs, NARIs - melatonin agonist serotonin modulator

Second line pharmacotherapy

TCAs, MAOIs

3 Phases for treatment with MDD

1. Acute Phase 2. Continuation Phase 3. Maintenance Phase

First-line treatment antidepressant due to safety in overdose and tolerability

SSRIs

An SNRI that potentiates the activity of NE and 5-HT by blocking their reuptake. Reported frequently during TCA therapy.

TCA

A generation SNRI that inhibits 5-HT in low doses and inhibits NE at high doses

Venlafaxine

a new generation SNRI that is a primary active metabolite of venlafaxine

Desvenlafaxine

A new generation SNRI with both 5-HT and NE reuptake inhibition across all doses

Duloxetine

A mixed serotonergic medication with dual action on serotonergic neurons, acting as both 5-HT antagonists and 5-HT reuptake inhibitors

Trazodone and Nefazodone

blocks b-adrenergic and histaminergic receptors (sedation and dizziness)

Trazodone

the long-acting release of this was approved by FDA

Trazodone

A mixed 5-HT which was declined due to hepatotoxic effect

Nefazodone

Block box labeling requirement from FDA warning describing rare cases of liver failure

Nefazodone

A serotonin andd A-adrenergic receptor antagonist that Enhances central noradrenergic and serotonergic activity through antagonism of central presynaptic a-adrenoceptor auto receptors and heteroceptors

Metazapine

Antagonizes 5HT receptors as well as Histamine receptors Helps lower anxiety and GI effects

Metazapine

Increases the concentration of NE, 5-HT, and DA within the neural synapse through inhibition of the MAO enzymes. Chronic therapy causes changes in receptor sensitivity.

MAOIs

Nonselective MAOis

Phenelzine and Tranylcypromine

Transdermal patch which allows inhibition of MAO-A and MAO-B in the brain, yet has reduced effects on MAO-A in the gut.

Selegilineb

Substrates of MAO-A

Serotonin, Norepinephrine, Dopamine, Tyramine

Tissue localization of MAO-A

Brain, gut, liver, placenta, skin

Substrates of MAO-B

Dopamine, Phenylethylamine

Tissue localization of MAO-B

Brain, platelets, lymphocytes