BB30044: Depression (SW)
Anxiety and depression are often linked: ~50% of people
with depression also have an anxiety disorder
However, anxiety & depression have distinct symptoms
Depression is heterogeneous in terms of cause:
Reactive = recognisable cause (e.g. stressful life
event) – easiest type to treat
Endogenous – no obvious cause (often resistant to
antidepressants)
Also bipolar disorder – alternating bouts of
depression and mania/hyperactivity (not addressed
in this lecture)
Major depressive disorder (MDD) – 10-15% lifetime risk,
higher prevalence in women (1.5-2 times)
Diagnostic criteria of MDD
Clinical diagnosis of MDD made if a minimum of 5 symptoms
(including one of the symptoms in italics) has been present for
at least 2 weeks, and disrupts normal occupational & social
functioning
Depressed mood
Decreased interest in pleasurable activities & ability to
experience pleasure (anhedonia)
Weight loss or weight gain, increased or decreased
appetite
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Feelings of hopelessness, worthlessness and guilt
Decreased ability to think or concentrate
Recurrent thoughts of death and suicide
Decreased ability to perform daily tasks efficiently
Risk factors for MDD
The heterogeneity of depression results from the variety of
influences/determinants. Notable risk factors which lead to an
, increased incidence of depression and comorbid illnesses
(obesity, diabetes & cardiovascular disease):
Stress: affects brain neurotransmitter systems (activation
of HPA axis and cortisol)
Innate immune system: inflammatory cytokines produced
by monocytes & microglia
Sex steroids: oestrogen & progesterone (may account for
sex bias)
GI system and adipose tissue: peptides ghrelin, leptin &
microbiome (gut-brain axis)
Cardiovascular: VEGF (vascular endothelial growth factor)
Gene polymorphisms that influence vulnerability:
SERT polymorphism: occurs in promoter of gene
encoding the serotonin transporter, main target for
antidepressants. Produces either short (14 repeats)
or long (16 repeats) SERT allele. Individuals
homozygous for short SERT allele have reduced SERT
levels and enhanced vulnerability to depression
relative to those homozygous for long SERT allele.
BDNF: V66M polymorphism linked to depression
Biogenic hypothesis
Initial hypothesis proposed in the 1950s
Depression is due to a decreased availability of 5HT
(serotonin) and/or noradrenaline
Evidence for hypothesis:
Drugs that reduce monoamines provoke depression:
RESERPINE (treats hypertension) depletes
monoamines from synaptic vesicles, limiting
monoamine release. Effectively treated hypertension
but increased incidence of depression.
Drugs that boost monoamine levels reduce
depression: e.g. SSRIs and MAO inhibitors.
IPRONIAZID (treats TB) is a MAO inhibitor, improved
mood of patients.
Link between depression and monoamine levels lead to
development of antidepressants, which boost extracellular
levels of monoamines.
Anxiety and depression are often linked: ~50% of people
with depression also have an anxiety disorder
However, anxiety & depression have distinct symptoms
Depression is heterogeneous in terms of cause:
Reactive = recognisable cause (e.g. stressful life
event) – easiest type to treat
Endogenous – no obvious cause (often resistant to
antidepressants)
Also bipolar disorder – alternating bouts of
depression and mania/hyperactivity (not addressed
in this lecture)
Major depressive disorder (MDD) – 10-15% lifetime risk,
higher prevalence in women (1.5-2 times)
Diagnostic criteria of MDD
Clinical diagnosis of MDD made if a minimum of 5 symptoms
(including one of the symptoms in italics) has been present for
at least 2 weeks, and disrupts normal occupational & social
functioning
Depressed mood
Decreased interest in pleasurable activities & ability to
experience pleasure (anhedonia)
Weight loss or weight gain, increased or decreased
appetite
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Feelings of hopelessness, worthlessness and guilt
Decreased ability to think or concentrate
Recurrent thoughts of death and suicide
Decreased ability to perform daily tasks efficiently
Risk factors for MDD
The heterogeneity of depression results from the variety of
influences/determinants. Notable risk factors which lead to an
, increased incidence of depression and comorbid illnesses
(obesity, diabetes & cardiovascular disease):
Stress: affects brain neurotransmitter systems (activation
of HPA axis and cortisol)
Innate immune system: inflammatory cytokines produced
by monocytes & microglia
Sex steroids: oestrogen & progesterone (may account for
sex bias)
GI system and adipose tissue: peptides ghrelin, leptin &
microbiome (gut-brain axis)
Cardiovascular: VEGF (vascular endothelial growth factor)
Gene polymorphisms that influence vulnerability:
SERT polymorphism: occurs in promoter of gene
encoding the serotonin transporter, main target for
antidepressants. Produces either short (14 repeats)
or long (16 repeats) SERT allele. Individuals
homozygous for short SERT allele have reduced SERT
levels and enhanced vulnerability to depression
relative to those homozygous for long SERT allele.
BDNF: V66M polymorphism linked to depression
Biogenic hypothesis
Initial hypothesis proposed in the 1950s
Depression is due to a decreased availability of 5HT
(serotonin) and/or noradrenaline
Evidence for hypothesis:
Drugs that reduce monoamines provoke depression:
RESERPINE (treats hypertension) depletes
monoamines from synaptic vesicles, limiting
monoamine release. Effectively treated hypertension
but increased incidence of depression.
Drugs that boost monoamine levels reduce
depression: e.g. SSRIs and MAO inhibitors.
IPRONIAZID (treats TB) is a MAO inhibitor, improved
mood of patients.
Link between depression and monoamine levels lead to
development of antidepressants, which boost extracellular
levels of monoamines.
