MOOD DISORDERS

(DEPRESSION PART 1)
DR. GORDON AMBAYO
KEMU UNIVERSITY
DEFINITION
• Mood can be defined as a pervasive and sustained emotion or feeling
tone, that influences a persons behavior and colours his or her
perception of being in the world.
• Mood is what the patient expresses about his or her feelings.
• Affect is what we observe about someone’s mood.
• Affect is the objective and behavioral expression of internal mood
states with concomitant observable motor components (i.e. facial and
other body movements).
DEFINITION/INTRODUCTION
• Mood disorders are a category of illnesses that describe a serious
change in mood.
• Mood disorders occur when a patient’s mood is not controllable and
causes impairment of daily life.
• Diminished volitional and cognitive expressions are generally, but not
always present.
INTRODUCTION/DEFINITION
• Depression is a mood disorder that causes a persistent feeling of
sadness and loss of interest.
• Also called major depressive disorder or clinical depression, it affects
how a client feels, think and behave and can lead to a variety of
emotional and physical problems
• Depression is the cluster of symptoms created when there is a
neurochemical imbalance in the brain.
INTRODUCTION
DSM 5 CHANGES
• Persistent depressive disorder replaces dysthymia.
• Disruptive mood dysregulation disorder, for children not meeting
criteria for BMD.
• Changes in bereavement:
Cut off no longer at 2 months.
Bereavement and MDD can occur together.
DEPRESSIVE MOOD DISORDERS (8)
– (DSM 5)
• Disruptive mood dysregulation disorder (Pediatric) New
• Major depressive disorder, single or recurrent episodes.
• Persistent depressive disorder (Dysthymia).
• Premenstrual dysphoric disorder.
• Substance/medication induced depressive disorder.
• Depressive disorder due to another medical condition.
• Other specified depressive disorder.
• Unspecified depressive disorder
ATYPICAL DEPRESSION
• Atypical depression is a subtype of major depression or dysthymic
disorder that involves several specific symptoms, including:
increased appetite or weight gain,
sleepiness or excessive sleep,
marked fatigue or weakness,
moods that are strongly reactive to environmental circumstances,
feeling extremely sensitive to rejection.
 OTHER MOOD DISORDERS.

• Bipolar disorder (mania - euphoric, hyperactive, over inflated ego,

unrealistic optimism),
• Bipolar II (hypomania and depression)
• Cyclothymia (a mild form of bipolar disorder),
• SAD (seasonal affective disorder).
RISK FACTORS
• 1) Chronic medical illness.
• 2) Chronic daily stress
• 3) Chronic Pain syndrome
• 4) Family history of depression.
• 5) Female sex.
• 6) Low income/job loss.
• 7) Low self esteem.
• 8) Low social support.
RISK FACTORS
• Prior depression.
• Single/divorced
• Traumatic brain injury/ brain surgery.
 AETIOLOGY
• BIOLOGICAL
a) Family and genetics
b) Neurotransmitters.
c) Neuroendocrine.
d) Immune system
e) Sleep dysfunction
 AETIOLOGY
(B)PSYCHOLOGICAL
a) Stressful life events.
b) Personality factors

(C) MEDICATION
(D) ALCOHOL
AETIOLOGY - BIOLOGICAL FACTORS
• Many studies have reported biological abnormalities in patients with
mood disorders.
• Until recently, the monoamine neurotransmitters-norepinephrine,
dopamine, serotonin, and histamine were the main focus of theories.
• A progressive shift has occurred from focusing on disturbances of
single neurotransmitter systems in favor of studying neurobehavioral
systems, neural circuits, and more intricate neuro regulatory
mechanisms.
AETIOLOGY - BIOGENIC AMINES
• Of the biogenic amines, norepinephrine and serotonin are the two
neurotransmitters most implicated in the pathophysiology of mood
disorders.
MONOAMINE HYPOTHESIS
MONOAMINE HYPOTHESIS
• The monoamine hypothesis of depression predicts that the
underlying pathophysiologic basis of depression is a depletion in the
levels of serotonin, norepinephrine, and/or dopamine in the central
nervous system.
• This hypothesized pathophysiology appears to be supported by the
mechanism of action of antidepressants: agents that elevate the
levels of these neurotransmitters in the brain have all been shown to
be effective in the alleviation of depressive symptoms.
MONOAMINE HYPOTHESIS
• However, intensive investigation has failed to find convincing evidence
of a primary dysfunction of a specific monoamine system in patients
with major depressive disorders.
• Understanding of the etiology of depression has been hampered by
the absence of direct measurements of monoamines in humans.
• However, the monoamine depletion paradigm, which reproduces the
clinical syndrome, allows a more direct method for investigating the
role of monoamines.
MONOAMINE HYPOTHESIS
• Results from such studies show that antidepressant responses are
transiently reversed, with the response being dependent on the class
of antidepressant.
• In contrast, monoamine depletion does not worsen symptoms in
depressed patients not taking medication, nor does it cause
depression in healthy volunteers with no depressive illness.
• Therefore monoamine hypothesis alone does not explain
pathogenesis of depression.
AETIOLOGY - BIOGENIC AMINES
• NOREPINEPHRINE. The correlation suggested by basic science studies between
the downregulation or decreased sensitivity of beta -adrenergic receptors and
clinical antidepressant responses is probably the single most compelling piece of
data indicating a direct role for the noradrenergic system in depression.
• Other evidence has also implicated the presynaptic beta 2-receptors in
depression because activation of these receptors results in a decrease of the
amount of norepinephrine released.
• Presynaptic beta 2-receptors are also located on serotonergic neurons and
regulate the amount of serotonin released.
• The clinical effectiveness of antidepressant drugs with noradrenergic effects-for
example, venlafaxine - further supports a role for norepinephrine in the
pathophysiology of at least some of the symptoms of depression.
AETIOLOGY - BIOGENIC AMINES
• SEROTONIN. With the huge effect that the selective serotonin
reuptake inhibitors (SSRis )-for example, fluoxetine (Prozac) have
made on the treatment of depression, serotonin has become the
biogenic amine neurotransmitter most commonly associated with
depression.
• Depletion of serotonin may precipitate depression, and some patients
with suicidal impulses have low cerebrospinal fluid (CSF)
concentrations of serotonin metabolites and low concentrations of
serotonin uptake sites on platelets.
BIOGENIC AMINES- DOPAMINE
• DOPAMINE. Although norepinephrine and serotonin are the biogenic
amines most often associated with the pathophysiology of
depression, dopamine has also been theorized to play a role.
• The data suggest that dopamine activity may be reduced in
depression and increased in mania.
• Drugs that reduce dopamine concentrations-for example, reserpine
(Serpasil)and diseases that reduce dopamine concentrations (e.g.,
Parkinson's disease) are associated with depressive symptoms.
BIOGENIC AMINES- DOPAMINE
• In contrast, drugs that increase dopamine concentrations, such as
tyrosine, amphetamine, and bupropion (Wellbutrin), reduce the
symptoms of depression.
• Two recent theories about dopamine and depression are that the
mesolimbic dopamine pathway may be dysfunctional in depression
and that the dopamine D1 receptor may be hypoactive in depression.
Other Neurotransmitter
Disturbances
• Acetylcholine (ACh) is found in neurons that are distributed diffusely
throughout the cerebral cortex.
• Cholinergic neurons have reciprocal or interactive relationships with
all three monoamine systems.
• Abnormal levels of choline, which is a precursor to ACh, have been
found at autopsy in the brains of some depressed patients, perhaps
reflecting abnormalities in cell phospholipid composition.
• Cholinergic agonist and antagonist drugs have differential clinical
effects on depression and mania.
Other Neurotransmitter
Disturbances
• Agonists can produce lethargy, anergia, and psychomotor retardation in
healthy subjects, can exacerbate symptoms in depression, and can
reduce symptoms in mania.
• These effects generally are not sufficiently robust to have clinical
applications, and adverse effects are problematic.
• Cholinergic agonists can induce changes in hypothalamic-pituitary
adrenal (HPA) activity and sleep that mimic those associated with severe
depression.
• Some patients with mood disorders in remission, as well as their never-ill
first-degree relatives, have a trait-like increase in sensitivity to cholinergic
agonists.
Other Neurotransmitter
Disturbances
• y-Aminobutyric acid (GABA) has an inhibitory effect on ascending
monoamine pathways, particularly the mesocortical and mesolimbic
systems.
• Reductions of GABA have been observed in plasma, CSF, and brain
GABA levels in depression.
• Animal studies report that chronic stress can reduce and eventually
can deplete GABA levels.
• By contrast, GABA receptors are upregulated by antidepressants, and
some GABAergic medications have weak antidepressant effects.
Other Neurotransmitter
Disturbances
• The amino acids glutamate and glycine are the major excitatory and
inhibitory neurotransmitters in the CNS.
• Glutamate and glycine bind to sites associated with the N-methyl-D-
aspartate (NMDA) receptor, and an excess of glutamatergic stimulation can
cause neurotoxic effects.
• Importantly, a high concentration of NMDA receptors exists in the
hippocampus.
• Glutamate, thus, may work in conjunction with hypercortisolemia to
mediate the deleterious neurocognitive effects of severe recurrent
depression.
• Drugs that antagonize NMDA receptors have antidepressant effects.
MEDICATION CAUSING DEPRESSION
• 1) Beta blockers.( e.g. Sectral-acebutolol, Inderal- Propranolol,
Tenormin-atenolol,)
• 2) Corticosteroids – e.g.Prednisolone.
• 3)Benzodiazepines – e.g. Alprazolam, Diazepam.
• 4) Anticholinergic drugs (Overactive bladder tolterodine, Parkinson’s
drugs e.g. carbidopa-levodopa, COPD e.g. iptraptopium, Asthma e.g
tiatropium, iptratropium, motion sickness e.g. scopolamine,
Extrapiramidal side effects e.g. benztropine)
• 5) Stimulants – e.g amphetamines.
• 6) Anticonvulsants e.g. carbamazepine.
MEDICATION CAUSING DEPRESSION
• 7) Proton pump inhibitors – e.g omeprazole.
• 8) Statins – e.g atorvastatin.
• 9) Drugs which affect hormones e.g. estrogen replacement therapy
for postmenopausal women, birth control pills.
• 10) Opioids – reduces respiration leading to tiredness and feeling of
depression.
• 11) Certain antibiotics e.g. Levofloxacin and Ciprofloxacin.
ALTERATIONS OF SLEEP
NEUROPHYSIOLOGY.
Depression is associated with a premature loss of deep (slow-wave)
sleep and an increase in nocturnal arousal.
• The latter is reflected by four types of disturbance:
• (1) an increase in nocturnal awakenings,
• (2) a reduction in total sleep time,
• (3) increased phasic rapid eye movement (REM) sleep, and
• (4) increased core body temperature.
ALTERATIONS OF SLEEP
NEUROPHYSIOLOGY
• The combination of increased REM drive and decreased slow-wave
sleep results in a significant reduction in the first period of non-REM
(NREM) sleep, a phenomenon referred to as reduced REM latency.
• Reduced REM latency and deficits of slow-wave sleep typically persist
after recovery of a depressive episode.
• Blunted secretion of GH after sleep onset is associated with decreased
slow-wave sleep and shows similar state-independent or trait-like
behavior.
IMMUNOLOGICAL Disturbance.
• Depressive disorders are associated with several immunological
abnormalities, including decreased lymphocyte proliferation in
response to mitogens and other forms of impaired cellular immunity.
• These lymphocytes produce neuromodulators, such as corticotrophin-
releasing factor (CRF), and cytokines, peptides known as interleukins.
• There appears to be an association with clinical severity,
hypercortisolism, and immune dysfunction, and the cytokine
interleukin- I, may induce gene activity for glucocorticoid synthesis.
OTHER FORMULATIONS OF
DEPRESSION COGNITIVE THEORY
• According to cognitive theory, depression results from specific cognitive distortions
present in persons susceptible to depression.
• These distortions, referred to as depressogenic schemata, are cognitive templates
that perceive both internal and external data in ways that are altered by early
experiences.
• Aaron Beck postulated a cognitive triad of depression that consists of (1) views about
the
• (1) Self-a negative selfprecept,
• (2) About the environment-a tendency to experience the world as hostile and
demanding, and
• (3) About the future - the expectation of suffering and failure.
• Psychotherapy consists of modifying these distortions.
LEARNED HELPLESSNESS
• The learned helplessness theory of depression, proposed by Martin Seligman,
connects depressive phenomena to the experience of uncontrollable events.
• Learned helplessness occurs when people or animals feel helpless to avoid
negative situations.
• For example, when dogs in a laboratory were exposed to electrical shocks from
which they could not escape, they showed behaviors that differentiated them
from dogs that had not been exposed to such uncontrollable events.
• The dogs exposed to the shocks would not cross a barrier to stop the flow of
electric shock when put in a new learning situation.
• They remained passive and did not move.
LEARNED HELPLESSNESS
• According to the learned helplessness theory, the shocked dogs learned
that outcomes were independent of responses, so they had both
cognitive motivational deficit (i.e., they would not attempt to escape
the shock) and emotional deficit (indicating decreased reactivity to the
shock).
• In the reformulated view of learned helplessness as applied to human
depression, internal causal explanations are thought to produce a loss
of self-esteem after adverse external events.
• Behaviorists who subscribe to the theory stress that improvement of
depression is contingent on the patient's learning a sense of control and
mastery of the environment.
DEPRESSIVE DISORDERS
• Specifiers are additional descriptors of severity, course or comorbid
clinical features.
• Bereavement is no longer considered an exclusion to depressive
disorder diagnosis within the first two months of loss.
• The coexistence of at least 3 manic/hypomanic symptoms (insufficient
for a manic episode) within a major depressive episode is indicated in
DSM 5 by the specifier with mixed features.
• There is no evidence that individuals with the mixed features
symptoms profile will develop bipolar disorder.
DEPRESSIVE DISORDERS
• Major depression with psychosis (Psychosis is specified according to
mood).
• Mood congruent psychotic features are consistent with underlying
mood.
• Mood incongruent psychotic features are generally bizarre and are
unexplained by mood symptoms.
• The presence of psychotic symptoms (Psychotic depression) is often,
associated with greater severity.
CLINICAL PRESENTATION
A) EMOTIONS
• Depressed mood
• Loss of interest or pleasure in most or all activities.
B) IDEATION
• Thought of worthlessness or guilt.
• Recurrent thougt about death or suicide.
CLINICAL PRESENTATION
C) SOMATIC SYMPTOMS
• Change in apetite or weight.
• Low energy.
• Psychomotor retardation or agitation.
• Poor concentration.
• Lack of sleep or excess sleep.
DIAGNOSTIC CRITERIA FOR MAJOR DEPRESSIVE
DISORDER (DSM V)

• Five (or more) of the following symptoms have to be present during the
same 2 week period and represent a change from previous functioning; at
least one of the symptoms is either (1) depressed mood or (2) loss of
interest or pleasure.
• Note: Do not include symptoms that are attributable to another medical
condition.
a) Depressed mood most of the day, nearly every day, as indicated by either
subjective report (eg., feels sad, empty, hopeless) or observation made by
others (eg., appears tearful).
(NOTE: in children and adolescence, can be irritable mood).
Diagnostic Criteria For Major
Depressive Disorder (DSM V)
• b) Markedly diminished interest or pleasure in all, or almost all,
activities most of the day (as indicated by either subjective account or
observation).
• c) Significant weight loss when not dieting or weight gain (eg. A
change of more than 5% of body weight in a month), or decrease or
increase in appetite nearly every day. (Note: in children, consider
failure to make expected weight gain).
Diagnostic Criteria For Major Depressive
Disorder (DSM V)
d) Insomnia or hypersomnia nearly every day.
e) Psychomotor agitation or retardation nearly every day (observable
by others, not merely subjective feelings of restlessness or being
slowed down).
f) Fatigue or loss of energy nearly every day.
Diagnostic Criteria For Major Depressive
Disorder (DSM V)
g) Feeling of worthlessness or excessive or inappropriate guilt (which may be
delusional) nearly every day (not merely self-reproach or guilt about being
sick).
h) Diminished ability to think or concentrate, or indecisiveness, nearly every
day (either by subjective account or as observed by others).
I ) 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.

PNEMONIC: SIG E CAPS

Diagnostic Criteria For Major Depressive
Disorder (DSM V)
B The symptoms cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
C The episode is not attributable to the physiological effects of a
substance or to another medical condition.
Diagnostic Criteria For Major Depressive
Disorder (DSM V)

D The occurrence of the major depressive episode is not better

explained by schizoaffective disorder, schizophrenia, schizophreniform
disorder, delusional disorder, or other specified and unspecified
schizophrenia spectrum and other psychotic disorders.
E There has never been a manic episode or a hypo manic episode.
Note: this exclusion does not apply if all of the manic-like or hypo
manic-like episodes are substance –induced or are attributable to the
physiological effects of another medical condition.
SIG E CAPS
• Depressed mood plus
• S- Sleep increased or decreased.
• I- Interest decreased in activities(anhedonia).
• G- Guilt or worthlessness.
• E- Energy decreased.
• C- Concentration difficulties.
• A- Appetite disturbance , weight loss or weight gain
• P- Psychomotor retardation/agitation
• S- Suicidal thoughts/plans
END OF PART 1
• THANK YOU
 EPIDEMIOLOGY
• Life time prevalence 4.4 to 16% in developed world.
• Male to female 1:2 in all communities.
COURSE OF ILLNESS
• Single episode occurs once in a lifetime.
• Recurrent episode must be preceded by a minimum of 2 months,
during which criteria for MDD were not met.
• Recurrence range from 50% in first one year to 85% during lifetime.
• Range of illness is 5-6 months.
• 20% become chronic, i.e. lasting more than 2 years.
Course of illness
• The improvement in volition and energy is generally a good sign of
initial response to treatment.
• However the lag Improvement in mood relative to volition may
result in despondency and suicidal behavior.
RISK AND PROGNOSTIC FACTORS.
A) ENVIRONMENTAL
• Adverse childhood experiences, especially when multiple.
• Stressful life events.
B) GENETIC AND PHYSIOLOGICAL
• First degree family members risk 2-4 times higher than that of the
general population.
• If one parent has a mood disorder a child will have 10 to 25% risk.
• If both parents have mood disorder the risk doubles.
RISK AND PROGNOSTIC FACTORS.
• COURSE MODIFIERS
• Lower recovery rate associated with, psychotic features, prominent
anxiety, personality disorders and symptom severity
• Persistence of even mild depressive symptoms during remission is a
powerful predictor of recurrence.
DOUBLE DERESSION
• Double depression refers to the co-existence of major depressive
disorder (MDD) and persistent depressive disorder (PDD), (the latter
was previously referred to as dysthymia).
• Research has shown that double depression tends to be more severe
than either MDD or PDD alone and that individuals with double
depression experience relapse more often than those with either
MDD or PDD alone.
DOUBLE DERESSION
• However, there is some research that indicates few differences exist
between double depression, MDD, and PDD; as a result, those
researchers conclude that double depression is not a distinct disorder.
REACTIVE DEPRESSION
• Reactive depression which depression caused by stressors is an old
terminology.
• It was used when depression was divided into reactive (caused by
environmental stressors) and endogenous depression (caused by
genetic and biological factors)
• This division is no longer used in DSM 5
LABORATORY TESTS
• Anti nuclear antibodies-autoimmune reaction e.g. in Lupus.
• Rheumatoid factor.
• ECG (Especially if tricyclic antidepressants will be used).
• HIV.
• Endocrine test when indicated.
LABORATORY TESTS
• Haemogram.
• Serum blood glucose.
• BUN concentration.
• Urinalysis.
• Urine toxicology screen.
• TSH
• LFT (Depression due to alcohol abuse)
• Pregnancy test (Avoid prescribing teratogenic drugs)
NEUROIMAGING
• Head CT scan useful in late onset depression or mood disorder,
screening for vascular disease, subdural hematoma and sub arachnoid
hemorrhage.
• MRI may be more sensitive, but availability and cost may be an issue.
• Functional MRI (fMRI).
• PET scan
Brain areas affected in depression
NEUROIMAGING
• POSITRON EMMISSION TOMOGRAPHY (PET) Scan finding:
• Most consistent is decreased anterior brain metabolism, which is more
pronounced on the left side.
• There is a relative increase in non dominant hemisphere activity.
• Greater left hemisphere reduction is seen in depression compared with
greater right hemisphere reduction in mania.
• Reduced cerebral blood flow or metabolism, or both, in the
dopaminergic innervated tracts of mesocortical and mesolimbic
systems.
• Antidepressants partially normalize these changes.
NEURIMAGING
• Increased glucose metabolism has been observed in several limbic
regions, particularly among patients with relatively severe recurrent
depression and a family history of mood disorders.
DEPRESSION
• END OF PART ONE
DEPRESSION PART 2
DR GORDON AMBAYO
OTHER BIOLOGICALY BASED CAUSES
Theories revolve around
• Altered neuroplasticity.
• Brain-Derived Neurotrophic Factor.
• Inflammation.
• Hypothalamic–pituitary–adrenal axis
NEUROPLASTICITY
• Neuroplasticity, also known as brain plasticity, or neural plasticity, is
the ability of the brain to change continuously throughout an
individual's life, e.g., brain activity associated with a given function
can be transferred to a different location, the proportion of grey
matter can change, and synapses may strengthen or weaken over
time.
• The aim of neuroplasticity is to optimize the neural networks
during neuron development, and physiological learning, as well as
after a brain injury.
NEUROPLASTICITY
• Research has showed that many aspects of the brain can be altered
(or are "plastic") even through adulthood.
• However, the developing brain exhibits a higher degree of plasticity
than the adult brain.
• Neuroplasticity can be observed at multiple scales, from microscopic
changes in individual neurons to larger-scale changes such as cortical
remapping in response to injury.
NEUROPLASTICITY
• Behavior, environmental stimuli, thought, and emotions may also
cause neuroplastic change through activity-dependent plasticity,
which has significant implications for healthy development, learning,
memory, and recovery from brain damage.
ALTERED NEUROPLASTICITY
• Recent studies have called attention to the role of altered
neuroplasticity in depression.
• A review found convergence of three phenomena:
• Chronic stress reduces synaptic and dendritic plasticity
• Depressed subjects show evidence of impaired neuroplasticity (e.g.
shortening and reduced complexity of dendritic trees)
ALTERED NEUROPLASTICITY
• Anti-depressant medications may enhance neuroplasticity at both a
molecular and dendritic level.
• The conclusion is that disrupted neuroplasticity is an underlying
feature of depression, and is reversed by antidepressants.
ALTERED NEUROPLASTICITY
• Post mortem studies and rat models demonstrate decreased neuronal
density in the prefrontal cortex thickness in depressed patients.
• Rat models demonstrate histological changes consistent with MRI
findings in humans, however studies on neurogenesis in humans are
limited.
• Antidepressants appear to reverse the changes in neurogenesis in
both animal models and humans
Brain-Derived Neurotrophic Factor.
• Brain-derived neurotrophic factor, also known as BDNF, is a protein
that, in humans, is encoded by the BDNF Gene.
• BDNF acts on certain neurons of the central nervous system and the
peripheral nervous system, helping to support the survival of existing
neurons, and encourage the growth and differentiation of new
neurons and synapses.
• In the brain, it is active in the hippocampus, cortex, and basal
forebrain- areas vital to learning, memory and higher thinking.
Brain-Derived Neurotrophic Factor.
• BDNF is also expressed in the retina, kidney, saliva, prostate, motor
neurons and skeletal muscles.
• BDNF is important for long-term memory.
• Although the vast majority of neurons in mammalian brain are
formed prenatally, parts of the adult brain retain the ability to grow
new neurons from neural stem cells in a process known as
neurogenesis.
Brain-Derived Neurotrophic Factor.
• Certain types of physical exercise have been shown to markedly
(threefold) increase BDNF synthesis in the human brain, a
phenomenon which is partly responsible for exercise induced
neurogenesis and improvement in cognitive function.
• Blood levels of BDNF(Brain derived neurotrophic factor) in depressed
patients increase significantly with antidepressant treatment and
correlate with decrease in symptoms.
Inflammation and oxidative stress
• General inflammation may play a role in depression.
• One meta analysis of cytokines in depressed patients found increased
IL-6 and TNF levels relative to controls.
• First theories came about when it was noticed that interferon therapy
caused depression in a large number of patients.
• Meta analysis on cytokine levels in depressed patients have
demonstrated increased levels of IL-1, IL-6, C-reactive protein, but not
IL-10 in depressed patients
Inflammation and oxidative stress
• Increased markers of oxidative stress relative to controls have been
found in patients with MDD. A marker of DNA oxidation, 8-Oxo-2'-
deoxyguanosine, has been found to be increased in both the plasma
and urine of depressed patients.
• This along with the finding of increased F2-isoprostanes levels found
in blood, urine and cerebrospinal fluid indicate increased damage to
lipids and DNA in depressed patients.
NEUROANATOMICAL
CONSIDERATIONS
Four brain regions are involved in emotions:
• A) Prefrontal cortex (Goals and appropriate response to obtain these
goals)
• B) Anterior cingulate (Integration of attention and emotional input
and cognition)
• C) The hippocampus (learning and memory. Also inhibitory regulation
of HPA axis)
• D) Amygdala ( Emotional significance and coordinating cortical
response).
Hypothalamic–pituitary–adrenal axis

• The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a

complex set of direct influences and feedback interactions among
three components: the hypothalamus, the pituitary gland (a pea-
shaped structure located below the thalamus), and the adrenal (also
called "suprarenal") glands (small, conical organs on top of the
kidneys).
• These organs and their interactions constitute the HPA axis, a
major neuroendocrine system that controls reactions to stress and
regulates many body processes, including digestion, the immune
system, mood and emotions, sexuality, and energy storage and
expenditure.
Hypothalamic–pituitary–adrenal axis

• Release of CRH from the hypothalamus is influenced by stress, physical

activity, illness, by blood levels of cortisol and by the sleep/wake cycle
(circadian rhythm).
• In healthy individuals, cortisol rises rapidly after wakening, reaching a peak
within 30–45 minutes. It then gradually falls over the day, rising again in
late afternoon.
• Cortisol levels then fall in late evening, reaching a trough during the middle
of the night.
• This corresponds to the rest-activity cycle of the organism.
• An abnormally flattened circadian cortisol cycle has been linked
with chronic fatigue syndrome, insomnia and burnout.
Hypothalamic–pituitary–adrenal axis

• The HPA axis has a central role in regulating many homeostatic

systems in the body, including the metabolic system, cardiovascular
system, immune system, reproductive system and central nervous
system.
• The HPA axis integrates physical and psychosocial influences in order
to allow an organism to adapt effectively to its environment, use
resources, and optimize survival.
Hypothalamic–pituitary–adrenal axis

• Increased production of cortisol during stress results in an increased

availability of glucose in order to facilitate fighting or fleeing.
• As well as directly increasing glucose availability, cortisol also
suppresses the highly demanding metabolic processes of the immune
system, resulting in further availability of glucose.
Hypothalamic–pituitary–adrenal axis

• The HPA axis is involved in the neurobiology of mood disorders and

other illnesses, including anxiety disorder, bipolar
disorder, insomnia, posttraumatic stress disorder, borderline
personality disorder, ADHD, major depressive
disorder, burnout, chronic fatigue syndrome, fibromyalgia, irritable
bowel syndrome, and alcoholism.
• Antidepressants, which are routinely prescribed for many of these
illnesses, serve to regulate HPA axis function.
Hypothalamic–pituitary–adrenal axis

• HPA axis activation is common in depressed patients.

• Frequently findings include elevated cortisol and corticotropin-
releasing hormone (CRH), nonsuppression on the dexamethasone
suppression test, a blunted adrenocorticotropic hormone (ACTH)
response to CRH, and hippocampal volume reduction.
• Evidence of HPA axis activation appears to have prognostic value and
is associated with increased risk of depression relapse and even
suicide.
Commonly used depression
symptoms severity scales
• Beck depression inventory. ( Self report)
• Hamilton rating scale for depression (Clinician rated)
• Montgomery Asberg Depression Rating scale( Clinician rated)
• Inventory of depressive symptoms (Self report and clinician rated
available)
Depression screening tools
• 1) Primary care evaluation of mental disorders (PRIME – MD)
• 1) Patient health questionnaire – PHQ 2
• 2) If PHQ 2 is positive for depression the PHQ 9 is administered.
• 3) In older adults, the 15 item Geriatric Depression Scale is
appropriate follow up test.
• If these screening tests are positive for depression, further evaluation
is needed to confirm that the patients symptoms meet the Diagnostic
and statistical manual of Mental Disorders criteria for diagnosis.
PRIME = MD
• Two questions from Primary Care Evaluation of Mental Disorders
MANAGEMENT
• Medical
• Psychological treatment.
• These can be given alone or in combination.
EXPLANATION TO PATIENT
• Antidepressants are not addictive or habit forming.
• Antidepressants take 2-3 weeks to begin working and need to be
taken for 4-6 months after full benefit is obtained to prevent relapse.
• Side effects occur and are expected.
• Drugs enable psychotherapy work.
• Regular review is important and needs to continue for at least 6
months.
MEDICAL MANAGEMENT
• Antidepressants
• Selective serotonin reuptake inhibitors.
• Give for 3 to 5 weeks at therapeutic dose to evaluate efficacy.
• Begin at recommended entry level dose and gradually
increase(weekly).
• If there is response continue at the maximally tolerated dose.
MEDICAL MANAGEMENT
• If no improvement – augment or switch to another antidepressant.
• Remission is usually 8-12 weeks.
• Augmentation is generally from another class of medication or
antidepressant with a different mechanism of action.
• If SSRIs e.g. fluoxetine don’t work change to Serotonin norepinephrine
reuptake inhibitors (SNRIs) e.g. duloxetine, venlafaxine,.
SIDE EFFECTS
• Initial side effects include:
• Gastrointestinal discomfort.
• Akathesia ie restlessness.
• Insomnia
• These are common in early stages and will remit, so don’t stop
treatment.
Side effects
• Sexual dysfunction is common and endures – STOP medication and
change.
• Bupropion and Mirtazapine have low frequency of side effects.
OTHER ANTIDERESSANTS
• Tricyclic antidepressants are quite effective although their use has
reduced.
• Mono amine oxidase inhibitors MAOI are rarely used nowadays.
• Use of MAOI involve avoiding tyramine in the diet eg cheese,
fermented foods.
Stopping medication
• Stopping medication should involve gradual lowering of dose.
PHYSICAL TREATMENT
• Electroconvulsive therapy (ECT).
• Repetitive transcranial magnetic stimulation (rTMS).
OUTCOME OF DEPRESSION
TREATMENT
• Five Rs
• Response 50% improvement
• Remission.(Absence of symptoms)
• Recovery. (Sustained period of remission)
• Relapse.( Return to major depression)
• Recurrence. (New episode after recovery AT LEAST 2 MOTHS).
REMISSION
• Remission, is defined as the disappearance of the diagnostic criteria
of depression for at least 2 consecutive months is the gold-standard
end point for evaluating antidepressant efficacy in long-term
controlled trials.
• Partial remission, defined as the persistence of residual symptoms,
is a risk factor for early relapse and subsequent recurrence; it is a
heterogeneous state, in which the persistence of even mild
symptoms reduces the hope of full functional recovery.
REMISSION
• The best criteria of high-quality remission are:
• The disappearance of the diagnostic criteria of depression for _2
months,
• A score of 1 on the Clinical Global Impression–Improvement scale,
• A score _3 on the Hamilton Rating Scale for Depression, and
• A return to premorbid general functional status.
MEDICAL COMPLICATIONS OF
DEPRESSION
• Coronary artery disease.
• Diabetes mellitus.
• Osteoporosis.
PROGNOSIS
• Prognosis of MDD is influenced by
• 1) Vulnerability factors (untoward life events and stressful
environmental influences).
• 2) Protective factors (supportive relationship)
• 3) Chronicity of the disease. (85% lifetime recurrence, 40-50% one
year remission rate).
PROGNOSIS
• Prognosis is positively influenced by:
• A long term strategy for medical and psychological management that
focuses on the patient, the family and environment and
• Strategy that maximizes the protective factors and minimizes the
vulnerabilities.
PROGNOSIS IN COMORBIDITY
• Depression has been associated with poorer outcomes in patients
with a variety of medical conditions such as:
• 1) Coronary artery disease
• 2) Diabetes mellitus
• 3) Stroke.
• Treatment of depression may reduce mortality from these conditions,
as well as help prevent suicide.
Pseudobulbar Affect (PBA)

• Patients exhibit mood-incongruent behavior.

• Laughing uncontrollably.
• Crying uncontrollably over something minor.
• Pseudobulbar Affect (PBA) is also known as emotional incontinence, labile affect, forced
crying, pathological emotionality, and emotional lability.
• PBA is resultant of a neurological disorder or a brain injury.
• Most commonly, individuals living with Multiple Sclerosis (MS), brain tumors,
ADHD, Parkinson’s disease, Alzheimer’s disease, Grave’s disease, and the after effects of a
stroke are most likely to exhibit pseudobulbar affect.
• Persons suffering from this condition have no control over their incongruent moods.
• This condition got the name pseudobulbar affect because its symptoms are similar to
those caused by a lesion on the medulla oblongata (i.e., a bulbar lesion).
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