Depression (wk 6) Flashcards
delusion
A belief that is clearly false and indicates an abnormality in content of thought
False belief cannot be explained by the person’s cultural or religious background or intelligence level
Belief is held despite being presented with evidence against it (“fixed” – firmly maintained)
Patient is convinced the delusion is real
causes of delusion
Can be due to: mental disorder, neurological or medical disorder
Examples: schizophrenic, substance abuse, bipolar disorder, major depressive disorder (MDD), delirium and dementia
hallucination
“A sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs”
Not under voluntary control
Vivid, clear, full force and impact of normal perceptions
Visual, auditory, tactile, olfactory, gustatory, nociceptive, thermoceptive, proprioceptive, equilibrioceptive
Formed (i.e. voice making a command) or unformed (i.e. non- specific sound)
With insight – px is aware that its not real only hallucination OR without insight – px is unaware and accepts the experience as reality
hallucination vs delusion vs psychosis
hallucination: “A sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs”
delusion: A belief that is clearly false and indicates an abnormality in content of thought
psychosis: Hallucination (without insight), delusion OR hallucination (without insight) and delusion
psychosis
Hallucination (without insight), delusion OR hallucination (without insight) and delusion
Loss of contact with external reality
Central component: Impaired reality testing
Can occur in psychiatric and neurological disorders Additionally:
Disorganized thoughts and impairment in cognitive function (i.e. reduced verbal fluency)
Mood changes
Reduced attention and concentration Sleep disturbances
what is the central component in psychosis?
impaired reality testing
delirium
Acute, fluctuating change in attention (reduced) and consciousness including disorganized thoughts
Altered consciousness: hypervigilant, unresponsive, near-coma, severe agitation
May include: psychosis; delusions and hallucinations, altered mood
how long does delirium last and what is it triggered by
Can vary in duration: days (typically) or months
Triggered by: change in medication, infection, surgery, trauma, stroke, withdrawal, very extensive list
depressive episode
Experience of low or depressed mood Loss of interest in most activities Additional possible symptoms:
Fatigue
Changes in appetite (and weight)
Feelings of worthlessness
Recurrent thoughts of death
Unexplained physical ailments unresponsive to treatment (i.e. digestive problems, pain)
can be seen in MDD< anxiety, bipolar, schizo, post stroke..
mania
Characteristics: increased talkativeness, rapid speech, decreased need for sleep, racing thoughts, distractibility, increase in goal-direct activity, psychomotor agitation
May include: elevated mood, mood lability, impulsivity, irritability, grandiosity
seen in bipolar, meds or substance, brain tumor
how long must mania last vs hypomania
Duration: 1 week or more OR if severity of symptoms warrants hospitalization
hypomania is 4 days
main dif between mania and hypomania
Differentiating factors from mania:
Duration: at least 4 days (rather than at least 1 week)
Does NOT cause major deficit in social or occupational functioning
Conditions: bipolar disorder, substances, neurological causes (i.e. encephalitis, dementia, lupus)
MDD risk factors
trauma, chronic pain or chronic disorders, low income, family history
mood physical and cognitive symptoms of MDD
Mood Symptoms
Physical Sx
Cognitive Sx
Feeling sad/ low
Lack of energy / tired
Slow thinking
Lack of interest in general
Difficulty sleeping; waking early
Difficulty concentrating
Anhedonia
Restless/ agitated
Slow movement
Low self-esteem
Weight loss
Forgetfulness
Lacking confidence
Low libido
Difficulty planning
Feelings of guilt or worthlessness
Low appetite/ overeating
Difficulty making decisions
Suicidal thoughts
which 2 components must be included in MDD
Depressed mood (subject report of observations of others) Anhedonia – loss of interest/ pleasure in almost all activities
These 2 sx must be present most of day, every day for at least 2 weeks in a row
how many symptoms for MDD total
at least 5ot
components of MDD
Category A – must include the first two components and a total of 5 or more components:
Depressed mood (subject report of observations of others) Anhedonia – loss of interest/ pleasure in almost all activities
These 2 sx must be present most of day, every day for at least 2 weeks in a row
Unintentional weight loss or gain (>5% in 1 mo) or significant change in appetite
Sleep disturbance (insomnia/ hypersomnia)
Psychomotor changes (agitations/ retardation)
Fatigue, low energy, decreased efficiency with routine tasks
Sense of worthlessness or excessive/ inappropriate guilt (i.e. guilt about being sick)
Impaired ability to think/ concentrate/ make decisions Recurrent thoughts of death, suicide ideation or attempts
Additional diagnostic requirements:
These sx must cause significant distress OR impair social, occupational or other important areas of function
Sx are not due to direct physiological effects of a substance (i.e. meds, drug abuse) OR medical condition (i.e. hypothyroidism)
Px has never experienced a manic or hypomanic episode
This condition is not better explained by schizophrenia spectrum or other psychotic disorders
leading theories of MDD
Monoamine hypothesis
Stress-induced depression hypothesis
Neurotrophic / Neuroplasticity hypothesis
Cytokine hypothesis/ Neuroinflammation hypothesis Circadian hypothesis of depression GABA-glutamate-mediated depression hypothesis
monoamine hypothesis of depression
what is it based on
Altered levels of monoamine neurotransmitters, specifically serotonin and noradrenaline, and/or dopamine cause depression
Based on antidepressant therapies that increase the presence/ function of one or more neurotransmitter resulting in reduced depression
Critiqued in that abruptly decreasing serotonin and/or dopamine doesn’t cause depression in a healthy person
Other neurochemicals are implicated in depression beyond these
Probable causes: genetics, environment, stress
stress induced depression hypothesis
which system on the body is impacted
HPA axis
stress induced depression hypothesis
Chronic stress leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
Prolonged, moderate stress is the problems, versus minor daily stresses OR one strong stressor
Examples: maternal stress, maternal smoking, early grave loss, child abuse
Early trauma may have more sig impact than in adult life (impact how HPA is developed in utero)
Chronic HPA activation leading to: excess cortisol secretion and pro-inflammatory agents that damage glia and neurons, interfere with neurogenesis and reduce glutamate and GABA
Clinical studies support this in some patients with severe depression: measurable increase in cortisol which is not reduced through negative feedback (also increased CRH)
Resistance of the glucocorticoid receptor (GR)
Antidepressants appear to restore the functioning of the GR and thus improve negative feedback and normalize cortisol levels
Critique: hypercortisolism is not a feature of all MDD cases AND not clear what causes HPA dysregulation (i.e. loss of GR sensitivity)
what does chronic HPA acitvation cause
excess cortisol secretion and pro-inflammatory agents that damage glia and neurons, interfere with neurogenesis and reduce glutamate and GABA
which receptor does cortisol bind to
glucocorticoid receptor –> for stress induced depression hypothesis and HPA dysregulation
what factor promotes neurogenesis
BDNFn
neurotrophic and neuroplasticity hypothesis of depression
Brain-derived neurotrophic factor (BDNF) promotes neurogenesis, regulates differentiation and growth of neurons
Neurogenesis may offer resilience against stress by enhancing the negative feedback loop with HPA
Observations:
Decreased BDNF gene expression, decreased BDNF levels and receptors in MDD patients
Increased cortisol can inhibit BDNF
Same triggers that elevated cortisol appear to block neurogenesis
Antidepressants
Have been demonstrated to stimulate neurogenesis in adult hippocampus (animal studies) – takes 4 weeks
Correlates with the 3-4 week expectation of achieve improvement in mood
which pro inflammatory markers are increased in MDD
TNFalpha, IL6, IL1, CRP, macrophage /monocyte activation
cytokine and neuroinflammation hypothesis
MDD px have increased levels of pro-inflammatory markers: TNFalpha, IL-1, IL-6, C-reactive protein (CRP) vs healthy px, as well as increased level of macrophage/monocyte activation
Frequent correlation b/w MDD and inflammatory conditions such as asthma, diabetes, arthritis, obesity, CAD
Animal studies: injecting pro-inflammatory cytokines induces depressive sx
Some antidepressants have anti-inflammatory properties
Earlier case reports observed improvement in mood in patients with treatment resistant MDD treated with anti- inflammatory medications, particularly in context of other inflammatory conditions (like IBD)
what produces melatonin and what regulated melatonin and what inhibits the production of melatonin
Light inhibits pineal gland from producing melatonin (by activating neurons with suprachiasmatic nucleus (SNC) of the hypothalamus)
SCN regulates production of melatonin throughout the body
Melatonin production increases at night during conditions of dark
circadian hypothesis of MDD
Stressful events lead to changes in diurnal molecular rhythms in cells that in vulnerable px triggers MDD
Bidirectional link with sleep disturbance and depression
Insomnia is a predisposing factor
Sleep deprivation therapy – reduces MDD sx (may resent the circadian clock)
Genes controlling circadian rhythms in anterior cingulate cortex are dysregulated in depression
Phase advance in cortisol rhythm and reduced amount of melatonin production seen in some patients with MDD
Altered circadian rhythms can also affect reward systems, particularly social interaction
Same 5-HT receptors have been implicated in both sleep rhythms and depression; serotonin is involved in phosphorylation of CLOCK protein, which regulate suprachiasmatic circadian rhythms
Sleep disturbances have also been correlated with pro- inflammatory cytokines
what excitatory neurotransmitter has a hypothesis for MDD
glutamate
excitatory neurotransmitter hypothesis of MDD
Glutamate may cause excitotoxicity resulting in neuronal atrophy and reduced synaptic connectivity
Stress induced changes may be accelerated in the presence of elevated Glu
Reduced GABA in CSF of MDD px – may be d/t change in serotonin which modulates GABA, which in turn modulates glutamate
Reduced GABA and glutamate within glial cells and neurons of the prefrontal cortex (PFC)
Astrocytes recycle glutamate and transport to presynaptic neurons
Elevated metabolism of glucose within same areas of PFC, and reduction of the gray matter in this region
Ketamine – modulates glutamate transmission Approved for tx of treatment resistant MDD
what drug modulate glutamate
ketamine
