Depression
DEPRESSION AS A HUMAN CONDITION
Depression is not a modern phenomenon.
Historical descriptions show that humans have long recognised
prolonged periods of altered psychological wellbeing.
Depression is therefore considered part of the human condition and
human biology, not a product of modern society.
WHY DEFINING DEPRESSION IS DIFFICULT
Normal mood variation
Mood naturally fluctuates within individuals:
o Some days people feel persistently low or irritable
o Other days mood is elevated, sometimes for identifiable
reasons (e.g. sunshine), sometimes not
Because mood fluctuates normally, it is difficult to define when low
mood becomes pathological.
Individual vs population thresholds
Individuals have different baseline mood ranges:
o A low mood that is normal for one person may be pathological
for another
This creates difficulty in defining diagnostic cut-offs at both:
o Individual level
o Population level
DSM approach
DSM attempts to define depression using symptom criteria and
subtypes.
However, DSM symptom lists:
o Are influenced by cultural and social context
o Do not necessarily translate well across populations globally
DSM therefore provides structure, but not a definitive biological
explanation.
DEPRESSIVE DISORDERS AND MAJOR DEPRESSIVE DISORDER
(MDD)
Depressive disorders as an umbrella
Depression is an umbrella term encompassing multiple depressive
disorders.
Major depressive disorder (MDD) is:
o The most common subtype
o The most studied in humans and animals
MDD is also referred to as clinical or unipolar depression
,Subtypes and demographics
Some depressive subtypes are:
o Age-specific
o Sex-specific
Hormonal fluctuations in biological females are suggested
contributors to some subtypes.
Prevalence
In populations where data are collected ~20% of people may meet
criteria for depression at some point in life
Course of illness
Depression is heterogeneous:
o Some individuals experience a single, reactive episode linked
to life events
o Others experience recurrent episodes
o In some cases, episodes occur without an obvious
precipitating factor
SEX DIFFERENCES IN DEPRESSION
Across populations, biological females have higher prevalence than
biological males.
The reason for this difference is unknown.
This suggests possible involvement of:
o Hormones
o Hormone receptors
Importantly:
o Sex hormones act widely in the brain
o Their effects are not limited to reproductive behaviour
o Incidental actions on mood-related circuits are likely
SYMPTOMS OF MAJOR DEPRESSIVE DISORDER
Core symptoms (must be present)
Persistent low mood
o Sustained over time
o Not just a temporary bad day
Anhedonia
o Reduced ability to experience pleasure
o Reduced valuation of previously rewarding activities
o Examples: hobbies, social interaction, exercise no longer feel
rewarding
Additional symptoms
Suicidal thoughts
, Reduced motivation
Appetite changes
Sleep disturbances
Feelings of guilt or worthlessness
Reduced energy
Difficulty concentrating or thinking
Increased restlessness
Diagnostic logic
Diagnosis requires:
o Symptoms present for >2 weeks
o A subset of symptoms (not all)
o At least one core symptom must be present
Overlap with other disorders
Many depressive symptoms overlap with:
o Anxiety disorders
o Other neuropsychiatric conditions
This blurs diagnostic boundaries.
LIMITATIONS OF HUMAN DEPRESSION RESEARCH
Subjective measurement
Many symptoms are subjective internal states:
o Pleasure
o Guilt
o Worthlessness
o Concentration
These cannot be measured directly.
Research relies on rating scales:
o Validated across large populations
o Still dependent on individual self-report on a given day
Placebo effects
Placebo effects are particularly strong in depression trials.
Contributing factors:
o Participants strongly want treatment to work
o Ethical constraints limit experimental manipulation
Result:
o Drugs may show strong early effects
o Later fail in larger trials
Heterogeneity problem
Symptom diversity may reflect:
o Different underlying biological mechanisms
Better stratification into subgroups may improve:
o Clinical trial design
o Treatment efficacy
DEPRESSION AS A HUMAN CONDITION
Depression is not a modern phenomenon.
Historical descriptions show that humans have long recognised
prolonged periods of altered psychological wellbeing.
Depression is therefore considered part of the human condition and
human biology, not a product of modern society.
WHY DEFINING DEPRESSION IS DIFFICULT
Normal mood variation
Mood naturally fluctuates within individuals:
o Some days people feel persistently low or irritable
o Other days mood is elevated, sometimes for identifiable
reasons (e.g. sunshine), sometimes not
Because mood fluctuates normally, it is difficult to define when low
mood becomes pathological.
Individual vs population thresholds
Individuals have different baseline mood ranges:
o A low mood that is normal for one person may be pathological
for another
This creates difficulty in defining diagnostic cut-offs at both:
o Individual level
o Population level
DSM approach
DSM attempts to define depression using symptom criteria and
subtypes.
However, DSM symptom lists:
o Are influenced by cultural and social context
o Do not necessarily translate well across populations globally
DSM therefore provides structure, but not a definitive biological
explanation.
DEPRESSIVE DISORDERS AND MAJOR DEPRESSIVE DISORDER
(MDD)
Depressive disorders as an umbrella
Depression is an umbrella term encompassing multiple depressive
disorders.
Major depressive disorder (MDD) is:
o The most common subtype
o The most studied in humans and animals
MDD is also referred to as clinical or unipolar depression
,Subtypes and demographics
Some depressive subtypes are:
o Age-specific
o Sex-specific
Hormonal fluctuations in biological females are suggested
contributors to some subtypes.
Prevalence
In populations where data are collected ~20% of people may meet
criteria for depression at some point in life
Course of illness
Depression is heterogeneous:
o Some individuals experience a single, reactive episode linked
to life events
o Others experience recurrent episodes
o In some cases, episodes occur without an obvious
precipitating factor
SEX DIFFERENCES IN DEPRESSION
Across populations, biological females have higher prevalence than
biological males.
The reason for this difference is unknown.
This suggests possible involvement of:
o Hormones
o Hormone receptors
Importantly:
o Sex hormones act widely in the brain
o Their effects are not limited to reproductive behaviour
o Incidental actions on mood-related circuits are likely
SYMPTOMS OF MAJOR DEPRESSIVE DISORDER
Core symptoms (must be present)
Persistent low mood
o Sustained over time
o Not just a temporary bad day
Anhedonia
o Reduced ability to experience pleasure
o Reduced valuation of previously rewarding activities
o Examples: hobbies, social interaction, exercise no longer feel
rewarding
Additional symptoms
Suicidal thoughts
, Reduced motivation
Appetite changes
Sleep disturbances
Feelings of guilt or worthlessness
Reduced energy
Difficulty concentrating or thinking
Increased restlessness
Diagnostic logic
Diagnosis requires:
o Symptoms present for >2 weeks
o A subset of symptoms (not all)
o At least one core symptom must be present
Overlap with other disorders
Many depressive symptoms overlap with:
o Anxiety disorders
o Other neuropsychiatric conditions
This blurs diagnostic boundaries.
LIMITATIONS OF HUMAN DEPRESSION RESEARCH
Subjective measurement
Many symptoms are subjective internal states:
o Pleasure
o Guilt
o Worthlessness
o Concentration
These cannot be measured directly.
Research relies on rating scales:
o Validated across large populations
o Still dependent on individual self-report on a given day
Placebo effects
Placebo effects are particularly strong in depression trials.
Contributing factors:
o Participants strongly want treatment to work
o Ethical constraints limit experimental manipulation
Result:
o Drugs may show strong early effects
o Later fail in larger trials
Heterogeneity problem
Symptom diversity may reflect:
o Different underlying biological mechanisms
Better stratification into subgroups may improve:
o Clinical trial design
o Treatment efficacy
