1 Dr.Wael Mansy, Ph.D. Department of Clinical Pharmacy College of Pharmacy / King Saud University Disorders of Mood.

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Dr.Wael Mansy, Ph.D.Dr.Wael Mansy, Ph.D.Department of Clinical PharmacyDepartment of Clinical Pharmacy

College of Pharmacy / King Saud UniversityCollege of Pharmacy / King Saud University

Disorders of MoodDisorders of Mood

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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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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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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.

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 manic-

like symptoms. Biologic vulnerability with hormonal changes

and psychological stressors all play a role.

It is characterized by the same symptoms as major depression, but

in a milder form. These include:

1. low self-esteem,

2. sleep and energy problems, and

3. 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.

The manifestations of mania include: 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.

Rapid cycling 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 long-

lasting 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. 17

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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 brain serotonin and norepinephrine caused depression, and drugs that increased brain 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.