Brazilian scientists have made a tantalizing discovery about bipolar
disorder. It looks as if bipolar disorder can damage DNA, and thus the
pathophysiology of bipolar disorder is not confined to the brain.
The lead researcher was Flavio Kapczinski, M.D., Ph.D., a professor of
psychiatry and director of the Bipolar Disorders Program and Molecular
Psychiatry Unit at Hospital de Clinicas & Federal University of Rio Grande
do Sul in Porto Alegre, Brazil. Their results are in press with Psychiatry
Kapczinski and his colleagues took peripheral blood cells from 32 bipolar
subjects without any comorbid medical illnesses and from 32 mentally and
physically healthy volunteers. The bipolar subjects used no medications except
for those prescribed for their bipolar illness. The control subjects were not
on medication. None of the subjects smoked.
The researchers assessed DNA damage in cells from the two groups of
subjects. They found that the damage was markedly greater in the cells from
the bipolar illness group than in those from the controls; the difference was
highly significant statistically.
Since the bipolar-illness subjects had no other medical illnesses,
Kapczinski and his colleagues thought it unlikely that the excess of DNA
damage in the subjects' cells was due to comorbid medical conditions. The
scientists also conducted an in vitro assay to determine whether the
medications used by the patients could induce DNA damage. The answer was
no—the psychotropic medications the bipolar subjects were taking did not
seem to explain the excess DNA damage in their cells. Thus the researchers
concluded that the damage was due to the subjects' bipolar disorder.
Kapczinski told Psychiatric News that he and his colleagues
believe that bipolar illness damages DNA by causing oxidative
stress—that is, oxidative damage—to cells in the body.
Their reasoning goes as follows. In this study, they found that the extent
of DNA damage in bipolar subjects' peripheral blood cells correlated with the
severity of the subjects' mania and depression as assessed by the Young Mania
Rating Scale and the Hamilton Depression Rating Scale. And in an earlier study
they found that oxidative stress in bipolar subjects' peripheral blood cells
increased during mania and depression. Thus it is logical that bipolar
disorder, especially during active illness phases such as mania and
depression, could trigger oxidative stress in cells and that this stress in
turn could damage DNA in those cells. Moreover, in an animal experiment, they
found that levels of DNA damage in both nerve cells and peripheral blood cells
correlated with increased oxidative stress.
But how might bipolar illness unleash oxidative stress in body cells in the
first place? By causing mitochondria in those cells to malfunction, Kapczinski
proposed. Not long ago, he said, researchers found that white blood cells
taken from bipolar subjects had abnormal mitochondrial electron transport,
which is the mechanism whereby cells deal with oxidative stress.
"Altogether, our findings of DNA damage in bipolar disorder seem to
be related to increased oxidative stress due to mitochondrial
dysfunction," Kapczinski said. "It is reasonable to suppose that
if mitochondrial dysfunction and consequently increased oxidative stress are
present in bipolar disorder, such changes would not be confined to the central
nervous system and would therefore be expressed in peripheral blood
Persons with bipolar disorder often have multiple chronic medical
illnesses, spanning nearly every organ system in the body (Psychiatric
News, November 17, 2006). An emerging body of evidence has linked DNA
damage with various medical conditions. Thus, these findings "provide an
important clue as to why patients with bipolar disorder have increased rates
of physical comorbidities," Kapczinski noted.
The results also have implications for psychiatrists, he suggested."
Clinically, this emerging body of evidence shifts the paradigm of
intervention in bipolar disorder. Treatment should be provided as early and
effectively as possible to avoid the detrimental effects of cumulative mood
episodes. Treating bipolar disorder effectively would not only improve the
lives of patients but also reduce their overall morbidity and mortality rates.
The investigation of new interventions using antioxidant agents as adjunct
therapy in bipolar disorder is warranted."
"Another intriguing possibility," he said, "is that in
the future the severity of bipolar disorder would be assessed not only
clinically, but also by means of lab tests such as levels of DNA damage and
The study was funded by Fundacao de Amparo a Pesquisa do Rio Grande do Sul,
Conselho Nacional de Pesquisa, Hospital de Clinicas de Porto Alegre, Federal
University of the Rio Grande do Sul, and the University of Caxias do Sul.
An abstract of "DNA Damage in Bipolar Disorder" can be
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