Biological Theories Of Manic-Depression
Q: Like every mental illness, there is no definitive evidence concerning
the etiology of manic-depression, also known as bipolar disorder. The
disorder is characterized by alternating periods of depression and mania
and occurs in 1% of the population. The depressive episodes can range in
severity from dysthymia to major depressive episodes. The major
depressive episodes are classified as periods of at least two weeks in
length during which sadness, lethargy, insomnia or excessive sleep,
increase or decrease in appetite, hopelessness, and suicidal ideation or
suicide attempts are present. Dysthymia is the milder form of
depression, during which suicidal ideation and attempts are not present.
Manic episodes are of at least two weeks in duration and are
characterized by euphoria, flight of ideas, grandiose delusions,
pressured speech, increased activity, and insomnia. Manic episodes can
also vary in intensity; the milder form of a manic episode is known as
hypomania and can be distinguished from a full-blown manic attack by its
lack of psychotic features and the lesser degree to which the individual
is impaired. In addition, there can also be mixed episodes, during which
both depressive symptoms and manic symptoms are present simultaneously.
The various types of episodes can combine in several ways to form three
separate disorders along the bipolar spectrum; bipolar I consists of
manic episodes and major depressive episodes as well as mixed episodes,
bipolar II consists of major depressive episodes and hypomanic episodes,
and cyclothymia consists of dysthymic episodes and hypomanic episodes.
Although individuals can obviously suffer from depressive episodes
without ever experiencing a manic episode, very few ever have only manic
episodes (DSM-IV, 1994).
A:Much of the existing body of knowledge concerning the causes of
manic-depression points to genetics. Many scientists have isolated
single genes to which they believe manic-depression can be attributed;
however, very few agree on which gene it is. Egeland (1987) announced
that she and her colleagues had found a gene that provided a strong
diathesis toward manic-depression on chromosome 11. Two different groups
of researchers (Detera-Wadleigh et al., 1987 and Hodgkinson et al.,
1987) found no connection between the same gene and manic-depression,
which led to the theory that more than one gene may be responsible for
the disorder. At the same time, Baron et al. (1987) announced they had
found a genetic link between manic-depression and a different gene. Both
Baron and Egeland later stated that their findings may be inconclusive
((1)). In 1993, Bredbecka et al. announced that the gene for
manic-depression is on the X-chromosome; the next year Berrettini et al.
(1994) reported to have found the gene that contributes to the disorder
on chromosome 18 and Straub et al. (1994) reported it to be on
chromosome 21. McMahon et al. (1995) found evidence to suggest that
manic-depression was more likely to be inherited from mothers than from
fathers, proposing that the gene for the disorder would be different in
women and men. At the same time, Stine (1995) published a paper
supporting the theory that the gene for manic-depression is on
chromosome 18. Gershon's research found that cases of manic-depression
in which there is a connection to chromosome 18 was not present in cases
where the disorder seemed to be inherited from the mother. In 1997,
Nurnberger stated that he and his colleagues found evidence that points
to as many as eight different chromosomes that may contain genes for
manic-depression, hypothesizing that the various genes may work in
different combinations ((2)); this might explain the different
manifestations of manic-depression. Recently, Stine reported that there
are "three or four locations that look about equally promising for
finding manic-depression genes," one of them chromosome 18. His research
also seems to support Gershon's; Stine believes that a predisposition
from chromosome 18 is present only if inherited from the father ((3)).
Another common theory of the etiology of manic-depression is
neurochemical malfunctions in the brain. If indeed manic-depression has
its origins in biology, something yet to be proven, and given the
theories that suggest neurotransmitter dysfunctions in depression,
perhaps the best solution to finding the cause of manic-depression would
be to investigate a chemical basis of the disorder. It seems as if the
best areas in which to start would be the same neurotransmitters that
have thus far been implicated in depression and the areas affected by
medications which alleviate symptoms of manic-depression.
The most widely used medication to treat manic-depression today is
lithium carbonate, an alkali salt. Lithium began to be utilized in the
treatment of manic-depression approximately fifty years ago and yet no
one knows exactly how it works ((4)), although it is known to be
effective for approximately 67% of individuals with manic-depression. It
has no known biological function and is not metabolized by the body; it
is excreted in its whole form by the kidneys. One theory suggests that
it alters membrane excitability by partially substituting for sodium.
Another hypothesis is that it is an antagonist at calcium binding sites;
this arose from findings that show low calcium levels in the
cerebrospinal fluid of depressed individuals and high levels in manic
individuals (Feldman et al., 1997). However, lithium is also used in the
treatment of major depressive disorder, without manic episodes,