MEDI7301 Final: Depressive disorders
Depressive Disorders
Major depressive disorder
Neurobiological &
neuropsychosocial
theories
Biological Genetic
30-40% genetic influence + 60-70% non-genetic
factors (childhood abuse, other lifetime trauma, low SES, marital
problems etc) explains MDD susceptibility
1st degree relatives of MDD individuals have a 3x
increased risk of MDD themselves
No specific gene or gene-environmental interactions
identified
Neurotransmitters (monoamine hypothesis)
Low 5HT activity
oSerotonin (5HT) is important for modulating
mood, aggression, sleep and appetite
oLow serotonin = high cortisol, high
glutamate & changes in immune function
oLow availability of serotonin-1A receptor
Low NAd activity
oNoradrenaline is important in modulating
drive, focusing thoughts, mood and appetite
oLow noradrenaline = impede activities of
these brain functions
oLow noradrenaline transporters in locus
coeruleus
Low DA activity
oDopamine (DA) is important in pleasure,
sex, thinking and psychomotor function
oLow dopamine = reduces experience of
pleasure and ease-of-thought processing
Neurotransmitters (GABA and glutamate
neurotransmission)
Reduction in GABA in prefrontal and occipital cortex
(acute depression) via low density and size of GABA interneurons &
low GABA-A receptor function -> contradictory evidence for GABA
hypothesis is lack of effect of GABA drugs on depressive sx
Dysfunctional glutamate system & abnormal NMDA
signaling
Neuroendocrine (stress hormones, cytokines)
Increased CRH and cortisol production (stress
hormones) -> it also leads to decreased appetite, disrupted sleep,
decreased libido and psychomotor alteractions
Increased CRH-secreting neurons in limbic brain
regions
Sickness behaviour (activation of inflammatory
system) mediated by pro-inflammatory cytokines IL1a, TNFa and
IL6 to impair central serotonin system -> anhedonia, fatigue,
psychomotor retardation, cognitive impairment
Childhood trauma and multiple stressors activate
these mechanisms
Neuroimaging (brain structure and function)
Reduced activation and activity of lateral frontal and
temporal cortices, insula and cerebellum
Large volume reduction of ventromedial prefrontal
cortex (left anterior cingulate & orbitofrontal cortex)
Moderate volume reduction of lateral prefrontal
cortex, hippocampus & striatum
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Reduction in glial cell density in dorsal, orbital and
subgenual prefrontal cortices & amygdala
Increased size of ventricles
Sulcal prominence
Increased activity in amygdala
Most solid evidence is volume reduction in left
subgenual cingulate cortex
Neurophysiology (circadian rhythm)
Increased REM length
Increased REM density (eye movements during REM
periods)
Reduced deep sleep (stage III and IV)
Significant changes in total sleep duration
Psychosocial Early adverse experience
Disruption of mother-infant relationships
Childhood abuse
Early traumatic events (war, natural disaster, family
death)
Environmental factors
Low SES, job loss, bereavement
Men are more likely to be depressed following
divorce, separation and work difficulties
Women are more likely to be depressed over
difficulties in social network, serious illness or death
Personality/ temperament factors
High neuroticism causing autonomic hyperarousal,
lability or negative biases in attention/ processing/ memory for
emotional material; anxious; poor self esteem
Co-morbid psychiatric diagnoses
Anxiety, substance abuse, developmental disability,
dementia, eating disorder)
Gene-
environment
interaction
5-HTTLPR gene & stressful life events -> depression
CRHR1 gene & childhood abuse -> adult depressive sx
FKBP5 gene & early trauma
Development and
course
Depressive episodes vary from 4-30 weeks for mild-moderate cases ---> 6
months for severe cases (25% up to 1 year)
Earliest reported symptoms are often changes in sleep or energy, and other
features accumulate over time
Children may present with enuresis, encopresis, school refusal or
behavioural problems
Adolescents may turn to substance abuse or antisocial behaviours as
coping mechanisms
Elderly may have social withdrawal, constipation, weight loss or
anhedonia
10-20% experience chronic course with persistent sx lasting over 2 years
Risk of recurrent depression is greatest when residual sx are present after
remission (eg low mood, anxiety, sleep disturbance, reduced libido, physical sx)
Mortality suicide rates for severe depressive episodes are 13%; this is 12-19%
for those requiring hospitalization
Risk factors Sex Female > male
Possible reasons - menstrual hormonal changes, post-partum,
domestic or violent abuse, 'caring for child' and compromising career
Age Onset between 25-50yo
Family hx Genetics
Depression, alcohol abuse, sociopathy
Childhood Loss of parent before age 11
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experiences Negative home environment (abuse, neglect, parental
tension)
Personality Insecure, dependent, obsessional (high neuroticism score)
Recent
stressors
Physical illness - severe pain, bedridden
Financial (low SES)
Legal
Multiple stressful events (job loss, marital difficulties, major
health problems, sleep deprivation)
Medications IFN, corticosteroids, cytotoxic agents, narcotic anagesics, anti-
Parkinsonian agents
Post partum < 6mths
Social network Lack of intimate, confiding relationships (single, separated,
divorced, widowed)
Social isolation
Culture War and disease burdened countries
Indigenous Australian
DSM-5 criteria At least everyday for 2 week period experiencing 5/9 following symptoms,
whereby at least one symptom must be depressed mood or anhedonia
S - sleep dysfunction (insomnia, hypersomnia)
A - appetite dysfunction (over or under eating or weight gain or loss)
D - depressed mood (or irritable mood in children)
A - anhedonia
F - fatigue/ low energy
A - agitation or retardation (psychomotor)
C - concentration diminished
E - esteem low/ guilty
S - suicidal ideation or attempt
Symptoms cause clinically significant distress or impairment in social,
occupational or other important areas for functioning
Symptoms are not attributable to physiological effects of a substance or to
another medical condition, response to significant loss (bereavement, financial ruin etc),
schizophrenic and other disorders, nor manic or hypomanic episode
Specifiers Anxious
distress
Patients with depression + at least 2 of following symptoms
Restlessness
Tension
Difficulty concentrating because of worry
Fear something awful may happen
Feeling of losing self control
Slower response to treatment & less likely to respond to anti-
depressant treatment
Psychotic
features
Unipolar major depression with psychotic features is a severe
subtype of MDD featuring more intense depressive sx + psychotic
delusions and hallucinations either mood congruent or incongruent
Mood
congruent
Most common
Depression + delusions or
hallucinations based around depressive themes of
guilt, nihilism, deserved punishment
oDelusion - possible
distortion of body image with delusions of their
decaying body, "I've committed a crime", "I've
got cancer"
oHallucination - hearing
noises making critical remarks to them, olfactory
hallucinations of their body emitting foul
decaying odours
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Document Summary
30-40% genetic influence + 60-70% non-genetic factors (childhood abuse, other lifetime trauma, low ses, marital problems etc) explains mdd susceptibility. 1st degree relatives of mdd individuals have a 3x increased risk of mdd themselves. Serotonin (5ht) is important for modulating mood, aggression, sleep and appetite o. Low serotonin = high cortisol, high glutamate & changes in immune function o o. Noradrenaline is important in modulating drive, focusing thoughts, mood and appetite o. Low noradrenaline = impede activities of these brain functions o coeruleus. Dopamine (da) is important in pleasure, sex, thinking and psychomotor function o. Low dopamine = reduces experience of pleasure and ease-of-thought processing. Reduction in gaba in prefrontal and occipital cortex (acute depression) via low density and size of gaba interneurons & low gaba-a receptor function -> contradictory evidence for gaba hypothesis is lack of effect of gaba drugs on depressive sx.
