Global Health Asia-Pacific July 2020 July 2020 | Page 49

1970s, the idea of schizophrenia as a chemical
disorder has not been conclusively demonstrated
because “no clear alterations in the brain dopamine
levels [of patients diagnosed with schizophrenia] were
confirmed,� according to the review Dopaminergic
hypothesis of schizophrenia: A historical perspective.
The authors of the review concluded that it’s
unlikely a single compound in the brain can explain the
variety of symptoms associated with schizophrenia,
but they nonetheless recommended continuing
research on the therapeutic potential of targeting
dopamine because of its crucial role in many mental
processes impaired in people diagnosed with
schizophrenia.
In a similar vein to schizophrenia, abnormal brain
chemistry became a popular explanation for another
ma�or form of psychological distress � depression.
The first compound in the class of drugs currently
known as antidepressants emerged in the 1950s
during an experiment testing its efficacy in treating
schizophrenia. Called imipramine, the drug failed in its
original aim but showed some mood-lifting properties
that were later confirmed in a study of forty depressed
individuals. Because of its success, several chemicals
similar to imipramine were subsequently developed
to treat depression and were all referred to as tricyclic
antidepressants due to their common three rings of
carbon atoms.
It wasn’t immediately clear why tricyclic drugs
were effective in relieving distress, but subsequent
studies pointed to the brain chemicals serotonin and
norepinephrine as possible answer.
While lab animals in a state reminding depression
were found to eliminate their stores of serotonin,
treating them with imipramine led to cheerful animals
with increased amounts of the chemical. In addition,
another tricyclic drug, amitriptyline, was shown to
raise levels of norepinephrine.
As a result, the psychiatrist Joseph Schildkraut put
forward the theory of a link between depression and
brain chemistry in 1965. “This hypothesis…proposes
that some, if not all, depressions are associated with
an absolute or relative deficiency of catecholamines,
particularly norepinephrine, at functionally important…
receptor sites in the brain,” he wrote in the American
Journal of Psychiatry.
Though Dr Schildkraut was simply suggesting a
way to make sense of the research on depression, his
idea soon gained traction.
“As discussion of the idea spread, though, it began
to seem less like a hypothesis and more like a claim.
And in the 1970s, the first discussions of depression
as a “chemical imbalance” appeared in the popular
literature. Publications from Cosmopolitan to the
New York Times explained that depression was
caused by deficits in essential brain chemicals, and
that antidepressants could fix the problem,� wrote
Professor Harrington.
In the 1980s, pharmaceutical companies latched
onto this idea as a framework to develop new
depression drugs that purported to normalise brain
chemistry without the serious cardiovascular side
effects associated with tricyclic medications.
These efforts led the �DA to approve �rozac in
1987, a new type of antidepressant that boosted
serotonin levels in the brain but didn’t cause heart
problems as side effects.
The drug became an instant blockbuster that
opened the floodgates to the creation of similar
serotonin-boosting substances, a group collectively
known as selective serotonin reuptake inhibitors
(SSRI), and an aggressive marketing campaign
painting depression as a disease caused by low
serotonin levels that could be easily treated with pills.
��ust as a cake recipe requires you to use flour,
sugar, and baking powder in the right amounts,
your brain needs a fine chemical balance in order to
perform at its best,” according to a TV ad touting the
benefits of the ��RI �oloft.
Over time, however, lack of robust data to pin
depression down to a simple chemical imbalance
led many psychiatrists to consider the theory as too
simplistic or utterly false.
“It’s a metaphorical interpretation of what happens
when somebody takes the medication [antidepressant]
and responds [to it],” Dr Michael B. First, Professor of
Clinical Psychiatry at Columbia University, told Global
Health Asia-�acific.
Boosted by marketing campaigns that needed
an easy concept to tout antidepressant benefits, he
added, this sort of metaphor has come to dominate
the understanding of depression in the popular
culture, but most psychiatrists are aware it’s an
oversimplification.
Far from being a straightforward chemical
Mental distress can put a heavy burden on people
Over time,
however, lack of
robust data to
pin depression
down to a
simple chemical
imbalance
led many
psychiatrists
to consider the
theory as too
simplistic or
utterly false
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