Etiologic considerations

Genetic Factors

Twin studies revealed that major depressive disorders could be heritable 37% of
the time. Patients who have more severe cases of major depressive disorder were
noted to have higher heritability estimates. Similarly, a genetic basis for bipolar
disorders is also evident based on research studies. Twin studies revealed
heritability estimates as much as 93%.

Although a specific gene has not yet been identified, molecular genetic studies
revealed
that 166 genetic loci are associated with the development of the major depressive
disorder and bipolar disorders.

Moreover, the serotonin transport gene's genetic polymorphism may be associated

with an increased vulnerability to developing depressive symptoms during periods
of stressful events.

A particular genetic polymorphism on gene DRD4.2, which influences dopamine

function, was also associated with the development of the major depressive
disorder. Because of the complexity of mood disorders, many researchers believe
that multiple genes may be involved in the development of mood disorders rather
than a single genetic aberration.

Neurobiological Factors

Neurotransmitters and receptor sensitivity

Three neurotransmitters are involved in the regulation of emotion, which may

affect a person's mood. These are norepinephrine, dopamine, and serotonin.

Decreased norepinephrine and dopamine levels are associated with

depression, while increased levels are associated with mania symptoms. Low
 serotonin levels are associated with the development of both manic and
depressive symptoms.

As mentioned in the previous module, dopamine is a neurotransmitter that

plays a role in the brain's reward circuitry.

Dopamine is associated with feelings of pleasure and motivation. Based on

research studies, decreased dopaminergic activity may be related to major
depressive disorder development.

This finding is congruent with studies that showed drugs that increase
dopamine levels might produce symptoms of mania.

Researchers have also demonstrated that patients with depressive disorders

may have heightened sensitivity to temporary decreases in serotonin levels.

This may be explained by the increased sensitivity of serotonin receptors,

which may be found among patients who are vulnerable to depression.

Brain abnormalities

Brain imaging studies show that certain areas of the brain may be implicated
in the development of mood disorders. The following brain structures are
associated with the development of major depression: amygdala, subgenual
anterior cingulate, dorsolateral prefrontal cortex, and hippocampus.

Functional imaging studies show that the amygdala and the subgenual anterior
cingulate have elevated activities in patients with major depressive disorder.

On the other hand, the dorsolateral prefrontal cortex and the hippocampus
have diminished activities in major depressive disorder patients. All the
mentioned brain structures are involved in emotional regulation. It is beyond
the scope of this module to discuss each neuroanatomic structure.

Psychological Factors
 Stressful life events appear to play a role in the development of the major
depressive disorder and bipolar mood disorders. Certain life events, such as
the loss of a loved one, loss of a job, relationship breakups, economic crises,
and health problems, are associated with the development of depressive
symptoms.

Studies show that stressful life events may be accountable for 20- 50% of
depression.

Moreover, the psychological causation of stressful life events for major

depressive disorder appears to be stronger on the first onset of the disease
rather than the successive recurrence of symptoms.

Moreover, one study also showed exposure to stressful life events prolongs the
recovery from episodes of mania, depression, or both compared to those who
lack exposure to such.

Some researchers hypothesize that stressful life events lead to biological

consequences that trigger mood instability leading to mood disorders.

Cognitive theories

There are cognitive theories that are associated with the development of major
depression. These are Beck's theory, Hopelessness theory, and Rumination
theory.

Beck's theory

This theory was formulated by Aaron Beck, an American psychiatrist. He

postulated that depression is associated with a triad of negative views of self,
the world, and the future.
 Based on this theory, people who are vulnerable to developing depression may
have acquired negative schema early in life through stressful life events such
as parental death, peer rejection, and childhood abuse (See Fig 7).

Beck believes that similar stressful life events activate an individual's negative
schema, which may produce negative thinking in the form of cognitive biases.

These are stored within a person's memory, which brings about an increased
tendency to process information in a predominantly negative manner, which
ultimately leads to a negative triad and depression.

Hopelessness theory

As the name implies, the hopelessness theory proposes that the most important
antecedent event to the development of depression is hopelessness. Based on
this theory, hopelessness is the expectation that good outcomes are no longer
possible and that people cannot change the outcome of a situation. The
cognitive thought of hopelessness was believed to arise from stressful life
events that lead to negative self-evaluation.

According to the hopelessness theory, there are two attributes that an

individual rationalizes as to why life stressors occur. First is the permanence
of the antecedent cause, whether it is a permanent or a temporary cause.

Second is the significance of the cause of multiple aspects of life or limited to

one aspect of living. This theory assumes that depression is brought about by
thoughts of hopelessness, which stems from attributing stressful live events to
having a permanent cause causing significant effects on multiple aspects of
life.

Based on this theory, an attributional style questionnaire was developed that is

designed to predict depressive symptoms, hopelessness, aspirations, and
self-esteem. Based on studies that utilized this questionnaire, hopelessness
predicted depressive symptoms, which supports this theory.