Depression - Pathophysiology Flashcards
What is depression? What are the different types?
is an affective disorder
- disorders of mood rather than thought/cognition
unipolar depression
- mood swings in one direction (most common)
bipolar depression
- oscillation between depression and mania
- onset is usually in adult life
What is the difference between depressive disorder, major depressive disorder and dysthymic disorder (dysthymia)?
depressive disorder
- a low state marked by significant levels of sadness, lack of energy, low self-worth, guilt or related syndromes
major depressive disorder
- severe pattern of depression that is disabling
- is not caused by factors such as drugs or a general medical condition
dysthymic disorder (dysthymia) - similar to major depressive disorder but less severe/disabling and more long-lasting (chronic)
What are the diagnostic features according to DSM-5?
must have 5 or more of the following symptoms
depressed mood most of the day, nearly every day
- in children and adolescents, it can be an irritable mood
markedly diminished interest or pleasure in all
significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day
- in children, consider failure to make expected weight gains.
insomnia or hypersomnia nearly every day
psychomotor agitation or retardation nearly every day
- observable by others
fatigue or loss of energy nearly every day
feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day
diminished ability to think or concentrate, or indecisiveness
recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
What are the physical, social and psychological features of depression?
physical
- slow/slurred speech
- change in appetite
- constipation
- loss of libido
- disturbed sleep
social
- not doing well at work
- absenteeism
- avoiding social activities
psychological
- anxious
- feeling hopeless
- tearful
- irritable
- suicidal or self harming
What are risk factors for depression?
chronic co-morbidities
- diabetes mellitus, chronic obstructive pulmonary disease, drug abuse, thyroid dysfunction
gender
- higher prevalence in women
age
- older age but age of onset has been decreasing
genetics and family history
What are differential diagnosis?
grief reaction anxiety disorders premenstrual disorder neurological conditions, - parkinson's disease, multiple sclerosis, dementia substances and adverse drug effects hypothyroidism obstructive sleep apnoeasyndrome
What are the theories underlining depression?
monoamine theory
- reduced activity of central noradrenergic and/or serotonergic systems
neuroendocrine theory
- hyperactivity/sensitivity of the HPA axis
What is evidence FOR the monoamine theory?
overall reduced activity of central noradrenergic and/or serotonergic systems causes depression
reserpine depletes brain of NA and 5-HT inducing depression
main antidepressant drugs increase 5-HT and/or NA in the brain
What is evidence AGAINST the monoamine theory?
would expect the effect to be quick by increasing 5-HT & NA but most antidepressant drugs take several weeks for therapeutic effect
- secondary adaptive changes are more important
some antidepressants have weak / no effect on amine uptake but still act as antidepressants
- trazodone
cocaine blocks amine uptake but has no antidepressant effect
decrease in 5-HT in bipolar disorder is linked to aggression rather than depression
What is the endocrine theory?
overactive/oversensitive HPA axis increases cortisol concentration which induces depression
hypothalamus releases corticotropin-releasing hormone (CRH)
CRH acts on anterior pituitary
release of adrenocorticotrophic hormone (ACTH)
cortisol release from adrenal cortex in response to ACTH in blood
- would expect high levels of cortisol (stress hormone) & CRH in CSF/ plasma
What is evidence FOR the endocrine theory?
injecting an animal with corticotrophin releasing hormone (CRH) induces depressive symptoms
increased cortisol concentration in the plasma
increased corticotrophin releasing hormone (CRH) in the cerebrospinal fluid (CSF)
How do genetic factors contribute to depression?
evidence of reduced hippocampal feedback in depression
- hippocampus regulates the HPA axis
= has glucocorticoid receptors which detect excess cortisol
imbalance of amygdala & hippocampus activity leads to depression
- amygdala stimulates the HPA axis to produce cortisol
- hippocampus suppresses the HPA axis to prevent excessive cortisol release
mutation of genes impacts HPA axis
How do environmental factors contribute to depression?
evidence shows decrease in glucocorticoid receptors in people with depression
- glucocorticoid receptor expression is regulated by early sensory experience
tactile stimulation just after birth activates 5-HT pathways to hippocampus
- 5-HT triggers long-lasting increased expression of glucocorticoid receptor gene
= results in increased glucocorticoid receptors in hippocampus
SSRIs increase glucocorticoid receptors in the hippocampus
What is the neuroplasticity and neurogenesis theory?
evidence that neuronal loss and decreased neuronal activity in hippocampus and prefrontal cortex induces depression
stress induces glutamate
Glu activates NMDA receptors
- leads to excitotoxicity, neuronal loss and depression
5-HT promotes neurogenesis during development by increasing production of BDNF
antidepressants and electroconvulsive therapy (ECT) promote neurogenesis in those regions
