Depression in Canada
- 10% of Canadians are affected by mood disorders
- suicide attempt seen in 15% of individual with major depressive disorders
- twice as prevalent in women (more likely to get help)
- men are more likely to be successful in suicide attempt (more lethal routes)
- men typically mask depression via somatic complaints (migraine, back pain, etc.)
Criteria for Major Depressive Disorder
Five (or more) symptoms must be present during the same two week period and represent a change from previous functioning
- at least one symptoms is either depressed mood or loss of interest or pleasure
- depressed mood, ahendonia, feelings of worthlessness, excessive guilt, decreased concentration, psychomotor agitation or retardation, insomnia, decreased libido, change in weight or appetite, thoughts of death of suicidal ideation
Risk factors for depression
- childhood emotional, physical, and sexual abuse
- prior episode of depression
- family hx
- lack of social support
- stressful life events
- current substance abuse
- economic difficulties
etiology of depression
genetic-environment interactions, neurobiological theory, genetic predisposition, synaptic transmission issues, biogenic Amin hypothesis
Other: negative beliefs, decrease in pleasure actives, parenting, family distress, social factors
Genetic-Environment Interactions role in depression
more common amongst 1st degree relative than in the general population
- Polymorphisms increasing the risk of depression
- Many genes play a role in depression
i.e genes determine metabolism of neurotransmitters, the amount of neurotransmitters, etc. - Serotonin Transport Gene: most studied in depressive disorders
- Contains polymorphism giving rise to two different alleles (long and short)
- Usually have two copies of gene allele in DNA
- Short Allele: slows down the synthesis of serotonin transporter reducing speed at which serotonin neurons can adapt to changes in stimulus
- Cause dysregulation of serotonin
Neurobiological theory in depression
deficiency or dysregulation in CNS concentrations of neurotransmitters
acetylcholine, dopamine, NE & E, serotonin, GABA
Where is acetylcholine found in the brain and what effects does it have?
- formed in many synapses of brain –> high concentration in basal ganglia and motor cortex
- can be excitatory or inhibitory depending on area
- under activity associated with Alzheimer’s
Where is dopamine found in the brain and what effects does it have?
- substantia nigra and ventral segmental area of midbrain
- derived from tyrosine
- usually excitatory
- involved in motivation, though, emotional regulation
- overactivity associated with schizophrenia and other psychotic disorders
Where is norepinephrine and epinephrine found and what effects does it have?
- locus ceruleus in brain stem derived from dopamine
- can be excitatory or inhibitory depending on the area
- associated with noradrenergic pathways to cerebral cortex, limbic system, and brain stem
Where is serotonin found and what effects does it have?
- Raphe nucleus in brain stem derived from tryptophan
- involved in regulation of attention and complex cognitive functions
- pathways to cerebral cortex, limbic system, and brain stem
- under activity thought to be involved with some depressions and OCD
Where is GABA found and what effects does it have?
- no single major source
- GABA and glycine usually inhibitory, glutamate is excitatory
- implicated in anxiety disorders
How do genetic predispositions contribute to depression?
BDNF found in high concentrations in the brain. Important for neuronal growth and synaptic changes.
- linked to stress, neurogenesis, and hippocampus atrophy in depression
- low levels of BDNF in depressive pt
How do Val / Met genes contribute to depression
Genetic Predisposition –> linked to BDNF
- Affects intracellular transport and secretion of BDNF
- People with met alleles increases vulnerability to depression (small hippocampus at birth, low hippocampus activity at rest, hippocampus hyperactivity during learning, relatively poor hippocampal memory function)
- Hippocampus in Depression: believed to modulate memory impairments, feelings of hopelessness and guilt, and suicide ideation
What is neurotransmission and how does it work (general)
nerve cells communicate with one another by a process called neurotransmission
1. The Synthesis of a transmitter substance
2. The storage and release of the transmitter
3. Binding of the transmitter to receptors on the postsynaptic membrane
4. Removal of the transmitter form the synaptic cleft
General Steps to Synaptic Transmission
- Synthesis and release
- receptors binding
- neurotransmitter removal
What is the biogenic amine hypothesis?
Serotonin & Norepinephrine: decrease levels in synaptic cleft (from decrease presynaptic release or decrease postsynaptic sensitivity) is underlying pathologic process in depression
- Reduction in serotonin synthesis causes depression AND depression can cause decrease in serotonin synthesis
Dopamine: decrease in depression, increased in mania
- Studies show frequency in depression is higher in Parkinson’s pt (due to decrease dopamine in substatia nigra)
What function does the prefrontal cortex have?
contains functional areas for reward, motivation, higher cognitive processes (executive functions), motor planning and execution, and regulating the expression of emotion
- reduced volume and capacity in depression
What function does the temporal love have?
integrates somatic (bodily), visual, and auditory information that is critical for recognition of familiar and responding to social contexts
- Interpreting emotions and responding to those emotions in a socially acceptable way and language
- Modulation and fine tuning emotion appropriate to level of intensity
- Planning, problem solving, intellectual insight, judgement, and expression of emotion
What function does the Amygdala have?
deep in medial temporal lobe in the primitive part of brain
- Gets signals from temporal and occipital lobe to communicate to hippocampus
- Important in emotional function and regulation, modulation of affective responses in social situations , sexual arousal, aggression, and fear response
- Increased blood flow and oxygen consumption during depression
- Abnormal neurodevelopment
What function does the limbic system have?
w/ basal ganglia are involved in development of mood disorders
- Parts are housed in temporal lobe
- Includes hippocampus, parahippocampal gyrus, cingulate gyrus, amygdala, and a bridge structure (fornix - connected the hippocampus with the hypothalamus)
What function does the HPA axis have in depression?
- With depression there is increased levels of CRF, cortisol
- With childhood stress —> chronic disinhibition of HPA axis, exaggerated stress response as adults
How does depression affect thyroid function
5-10% of pt w/ depression have decreased thyroid function
- Given thyroid replacement therapy to reverse process to speed up metabolism and speed up response to depression treatment
How does depression affect the sleep-wake cycle
common in many mental illnesses —> early warning sign of relapse
- Normal sleep cycle is reversed in pt w/ depression (i.e reach deep sleep early in cycle)
- Regulated by circadian clock
- Melatonin from pineal gland is thought to help regulate sleep wake cycle
How does depression affect circadian rhythms?
Circadian abnormalities of mood, sleep, temp, and neuroendocrine secretion w/ depression
- May take weeks to months to fix after treatment
- Importune to normalize cycle ASAP
