Biographical
Information:
Dr. Barondes
received his medical degree from Columbia University
College of Physicians and Surgeons in 1958, and was
then an intern at the Peter Bent Brigham Hospital in
Boston from 1958 to 1960. From 1960 to 1963, he was
a research fellow at the National Institute of Health
in Bethesda, where he learned biochemistry and molecular
biology in the laboratory of the Nobel Laureate Marshall
Nirenberg. He then returned to the Boston area as a
resident in psychiatry at McLean Hospital and the Massachusetts
General Hospital from 1963 to 1966, and has spent the
remainder of his career in psychiatry departments. He
was at the Albert Einstein College of Medicine in New
York from 1966 to 1969, at the University of California
at San Diego School of Medicine from 1969 to 1986, and
since 1986 he has been at the University of California
at San Francisco School of Medicine (UCSF). He was Chairman
of the Department of Psychiatry at UCSF and Director
of the Langley Porter Psychiatric Institute from 1986
to 1994. Since 1994, he has been Director of the Center
for Neurobiology and Psychiatry at UCSF. Dr. Barondes
pioneered the introduction of biochemistry and molecular
biology to psychiatry departments. It is still rare
to find faculty members in psychiatry departments who
do this kind of basic research, and at the time he began
doing this in 1966, it was unheard of. He has worked
on organisms ranging from slime molds, through mollusks
and rodents, to humans, and has made substantial contributions
in every area in which he has worked. During the last
five years he has turned his attention to the molecular
genetics of mental illness, with particular focus on
the genetics of manic depressive disorder. He has written
widely on the evolution of biological psychiatry, and
on the impact that modern molecular genetics can have
on psychiatry. This was the focus of his lecture.
Biological
Psychiatry:
Dr. Barondes
began his lecture by reminding the audience that the
best known of all psychiatrists, Sigmund Freud, was
at heart a biologist (in fact he referred to himself
repeatedly in his writings as a neurophathologist).
However, Freud's efforts to explain mental processes
in biological terms were never successful, and he turned
to analysis when he despaired of ever having enough
biological information about the brain to understand
mentation. Under Freud's leadership, psychoanalysis
flourished, and was the main therapeutic tool of psychiatrists
through much of the twentieth century. After this overview
and perspective on the conflict between psychoanalysis
and biological psychiatry, Dr. Barondes turned to an
examination of manic depressive illness, which together
with its more common cousin, severe depression, affects
a very large percentage of our population. He provided
several fascinating case histories of manic depressive
illness to illustrate its course, and then launched
into a discussion of drugs that have proven to be very
effective in its treatment. First, he described the
discovery that lithium could be an effective treatment
for manic depressive illness. This discovery, like so
many important discoveries in the biological sciences,
was serendipitous. The pharmocologist, John Cade, noted
that lithium injections made guinea pigs lethargic,
and concluded from this that lithium might be an effective
treatment for the manic phase of manic depressive disorder.
This description of the first test of lithium in therapeutic
doses in a manic depressive patient was a particularly
compelling part of Dr. Barondes' lecture. It is now
known that lithium blocks an inositol triphosphate phosphatase,
thus preventing the regeneration of phosphatidylinositol-bis-phosphate,
an essential second messenger molecule in the nervous
system. Although it is not known with certainty that
this effect of lithium is responsible for its therapeutic
actions, it seems likely that it does play a role. However,
an important finding that remains unexplained is that
lithium blocks this phosphatase immediately upon administration,
whereas the therapeutic effect of lithium in manic depressive
illness takes several weeks to become apparent.
Dr. Barondes
then went on to discuss the antidepressants, which are
blockers of the re-uptake of the neurotransmitters norepinephrine
and serotonin. Imipramine was the first of these re-uptake
blocker anti-depressants, introduced for therapeutic
purposes in 1957. The most effective anti-depressants
today are blockers of serotonin uptake, including Prozac,
which was introduced in 1987. Prozac works as well as
Imipramine, and has more limited side effects. In addition,
Prozac and its relatives have the completely unexpected
benefit of alleviating the symptoms of a variety of
neuroses. During the last five years, Prozac has, to
a large extent, displaced analysis as a treatment for
neurosis, even among those psychiatrists who were previously
committed psychoanalysts.
Finally,
Dr. Barondes discussed the next potentially great biological
trend in psychiatry, molecular genetics. He emphasized
that the use of molecular genetics in the diagnosis
and treatment of psychiatric disorders is only in its
infancy, but he has every expectation that it will have
enormous impact. One problem is that the genetics of
many human diseases, including psychiatric disorders,
may be very complex, which makes them exceptionally
difficult to study. However, Dr. Barondes is absolutely
convinced that the influence of genetics on the way
we think about psychiatric disorders cannot be over-emphasized.
He and his colleagues have been studying several family
pedigrees in which manic depressive illness occurs with
astonishingly high frequency. They have localized a
gene contributing to this trait to a relatively small
region of the human genome, and are engaged in a concerted
effort to clone and characterize this gene. Success
in this effort will open a new chapter in biological
psychiatry.
