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Disorders of Mood
Dr.Wael Mansy, Ph.D.
Department of Clinical Pharmacy
College of Pharmacy / King Saud University
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Mood disorders are
Disorders of emotion (mania and depression) rather
than disturbances of thought.
Although relatively common, they are highly
underdiagnosed and undertreated illnesses.
Mood disorders include:
 Major depression and,
 bipolar (manic-depressive) disorders.
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is among the leading causes of disability worldwide,
with a lifetime incidence in the United States of 20% in women and
12% in men.
•The prevalence of major depression among women is double that in
men.
•The prevalence of
is approximately 1.5% in the
population at large, approximately equally distributed between men
and women.
•Men more often have the manic phase in the initial episode, whereas
women more often have the depressed phase as the initial episode.
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
Approximately 20% to 40% of adolescents who present with
major depression develop bipolar disorder within 5 years.

The average age of onset of bipolar disorder is the mid- to late
twenties, and for depression, the mid-thirties; however, the age of
onset of both disorders has been decreasing.

In addition, the incidence of depression appears to be
increasing.
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
Depression can vary in intensity and often is recurrent.

A first episode of depression that occurs after 65 years of age can be a precursor
to dementia and should precipitate both assessment and treatment of the depression,
as well as a thorough evaluation for dementia.

Early intervention often greatly retards the progression of dementia,
maintaining the individual’s independence and quality of life.
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(characterized by a
persistent unpleasant mood) and
(characterized by chronic mild depressive
symptoms).
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 It is characterized by the following:
1) depressed mood,
2) anhedonia (inability to experience pleasure),
3) feelings of worthlessness or excessive guilt,
4) decreased concentration,
5) psychomotor agitation or retardation,
6) insomnia or hypersomnia,
7) decreased libido,
8) change in weight or appetite, and
9) thoughts of death or suicidal ideation.
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•Depression has various sub-classifications distinguished by
symptom patterns.
1. Depression with melancholic features is characterized by:
• depression that is worse in the morning,
• insomnia with early morning awakening,
• anorexia with significant weight loss,
• psychomotor retardation or agitation,
• excessive or inappropriate guilt,
• loss of interest in activity,
• inability to respond to pleasurable stimuli, and
• a complete loss of capacity for joy.
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2. The symptoms of Atypical depression are opposite those
of melancholic depression; it is characterized by a depression that
becomes worse as the day progresses, overeating, and hypersomnia
(excessive sleep).
3. Depression with psychotic features involves the presence of
delusions or hallucinations that may or may not be mood-congruent.
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
The classification of depression with catatonic features is applied when
symptoms include excessive mobility or motoric immobility, extreme
negativism, repetitive speech, and peculiar voluntary movements.

The chronic specifier is applied if symptoms of major depression persist for
2 or more years.

A postpartum specifier is included if the onset is within 6 weeks of
childbirth. Most women experience some mild letdown of mood in the
postpartum period. For some, the symptoms are more severe and similar to
those seen in serious depression, with increased emphasis related to the infant
(obsessive thoughts about harming it or an inability to care for it).
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When psychotic symptoms occur, there is frequently
associated sleep deprivation, volatility of behavior, and maniclike symptoms. Biologic vulnerability with hormonal changes
and psychological stressors all play a role.
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
It is characterized by the same symptoms as major depression, but
in a milder form. These include:
1.
low self-esteem,
2. sleep
3.
and energy problems, and
appetite disturbances.
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
The insidious and chronic nature of this disorder often makes it
difficult for the person dealing with this illness to separate it from
the usual manner of functioning and to recognize the symptoms
as part of an illness.

Persons with dysthymia are at risk for development of major
depression and other psychiatric disorders, including substance
abuse disorders.
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 Although Bipolar depression, or manic-depressive
disorder, also has multiple sub-classifications, all of which
are usually characterized by episodes of elation and
irritability (mania) with or without episodes of depression
mania without associated depression (unipolar mania) can
occur, it is rare.
 Mania, in persons with bipolar disorder, can be
precipitated by antidepressant medications and the somatic
therapies used to treat depression, such as electroconvulsive
therapy.
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
The manifestations of mania include:
1. decreased need for food and sleep,
2. labile mood,
3. irritability,
4. racing thoughts,
5. high distractibility,
6. rapid and pressured speech,
7. inflated self-esteem, and
8. excessive involvement with pleasurable activities,
some of which may be high risk.
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In its minor forms, the subjective experience of mania can be quite
pleasurable to the individual, with a heightened sense of well-being and
increased alertness.
The severity of manic symptoms runs the gamut from a condition called
cyclothymia, in which mood fluctuates between mild elation and
depression, to severe delusional mania.
Mania may begin abruptly within hours or days, or develop over a few
weeks.
Bipolar episodes, left untreated, become more severe with age.
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
Rapid cycling is said to occur when an individual has four or more shifts in
mood from normal within a 1-year period.

Women are more likely than men to be rapid cyclers.

Kindling is a hypothesized phenomenon in which a stressor creates an
electrophysiologic vulnerability to future stressful events by causing longlasting changes in neuronal function.

This may be the basis for the phenomenon of rapid cycling in bipolar
depression. The more frequently a person has a shift in mood, cycling into
either mania or depression, the easier it becomes to have another episode.
There now is evidence that many psychiatric disorders, not just bipolar
disorder, are subject to this phenomenon. The better the control of the
illness and the fewer cycles an individual has, the better his or her quality of
life is likely to be.
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
In some cases of familial major depressive disorder and bipolar
disorder, PET and MRI studies have demonstrated a reduction in
the volume of gray matter in the prefrontal cortex, with an
associated decrease in activity in the region.

Structural
imaging
studies
have
consistently
found
abnormalities in the subgenual prefrontal cortex in patients with
familial bipolar disorder, a region related to responses to
emotional experiences.
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
Clinical studies have suggested that this area of the brain is
important for mood states and has extensive connections with
the limbic system.

Physiologically, there is evidence of decreased functioning in the
frontal and temporal lobes, although it is not known if this is a
cause or an effect of depression because the activity returns to
normal with the resolution of the symptoms .

The amygdala tends to have increased blood flow and oxygen
consumption during depression. Unlike those areas where
function returns to normal with the resolution of depression, the
amygdala continues to be excessively active for 12 to 24
months after the resolution of depression.
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
It is hypothesized that relapse into depression is more likely to
occur if medications are decreased or stopped before the
amygdala returns to normal functioning. Other studies suggest
abnormal neurodevelopment of the amygdala.

Neurologic disorders of the limbic system and basal ganglia
are also involved in the development of mood disorders.

A number of neurotransmitters, serotonin and norepinephrine
in particular, are implicated in depression.
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
The biogenic amine hypothesis suggests that decreased levels
of these neurotransmitters in the synaptic cleft, due either to
decreased
presynaptic
release
or
decreased
postsynaptic
sensitivity, is the underlying pathologic process in depression.

The hypothesis is derived from the fact that drugs that
depleted
depression,
brain
and
serotonin
drugs
that
and
norepinephrine
increased
brain
caused
levels
of
norepinephrine and serotonin decreased depression.

Dopamine activity has also been implicated in mood disorders,
with decreased dopamine activity found in depression, and
increased dopamine activity in mania.
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
It has become increasingly clear, however, that a simple
decrease in the concentration of amines in neuronal synapses
cannot entirely explain the complexities of depression.

Neuro-modulatory systems in the brain interact with each other
in complex ways. For example, cholinergic and GABA-ergic
pathways also may play a role in the development of depression
because both of these pathways influence the activity of brain
norepinephrine neurons.

Disturbances in the function of the hypothalamic-pituitary
adrenal (HPA) axis also may play a critical role in depression.
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
In the general population, cortisol levels usually are flat from
late in the afternoon until a few hours before dawn, when they
begin to rise. In persons with depression, cortisol levels spike
erratically over the 24 hours of the day. Cortisol levels return to
the normal pattern as depression resolves. In 40% of those
diagnosed
with
depression,
hypersecretion
of
cortisol
is
resistant to feedback inhibition by dexamethasone, indicating a
dysfunction of the HPA axis.

About 5% to 10% of persons with depression have a decrease in
thyroid function, in which case the person is less likely to have a
vigorous response to medical intervention.
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
Alteration in the sleep–wake cycle is common in many mental illnesses
and often is one of the prodromal signs of relapse.

Researchers have found that the normal sleep cycle is reversed in
depression.

Persons with depression often have what is called dream pressure
sleep. The depressed individual falls into light and dream-state sleep
early in the sleep cycle and reaches deep stage 4 sleep only late in the
sleep cycle. This finding helps explain why many inpatients report they
did not sleep all night and the staff reports that the patient was asleep
all night. Although the sleep cycle usually reverts to normal after the
resolution of the depression, it may not be completely normal for
weeks to months. Decreasing or halting medications before the sleep
disturbances resolve may lead to a relapse of depressive symptoms.
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
Fatigue and hypersomnia are common among individuals with
depressive disorder, and individuals who complain of chronic
fatigue are at risk for development of major depressive
disorder.

Circadian rhythms also are an area of serious research interest.
A specific type of depression known as seasonal affective
disorder (SAD) is triggered for persons in the winter by the
shortening of daylight hours as fall commences, with symptoms
of depression usually resolving in the spring when daylight
hours again lengthen.
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
Circadian rhythm considerations are also critical in symptom
management for persons with bipolar depression. One of the
fastest ways to precipitate a manic episode is for the individual
to stay up all night. It is not unusual for a first manic episode to
occur when someone “pulls an all-nighter” studying for final
examinations.

Persons with bipolar disorder should have a fairly rigid schedule
for sleeping and awakening if cycling is to be minimized.

Although exercise is important, the person with bipolar disorder
should exercise before mid afternoon to prevent the normal
increase in metabolic rate from disrupting the sleep cycle.
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*The DSM-IV-TR ( The Diagnostic and Statistical Manual of Mental
Disorders published by the American Psychiatric Association)
diagnostic criteria for a major depressive episode include the
simultaneous presence of five or more of the aforementioned
symptoms during a 2-week period, and these must represent a
change from previous functioning.
* It is estimated that 50% of hospitalized patients with coronary artery
disease have some depressive symptoms, with up to 20% developing
major depression. Depression negatively impairs prognosis, affecting
both behavioral and physiologic aspects of recovery, and increases the
risk of death.
*Bipolar disorder is diagnosed on the basis of the pattern of
occurrence of manic, hypomanic, and depressed episodes over time
that are not due to medications or other therapies. The frequency,
duration, and severity of the manic or depressive periods are unique
to each individual.
*Mania, particularly in its severe delusional forms, also needs to be
differentiated from schizophrenia or drug-induced states.
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