Question:
Prescription for Trouble: Antidepressant treatments might rewire young brains?
Answer:
Prescribing antidepressants to children and pregnant women is becoming
increasingly common. However, it hasn't been clear whether these medications
pose a risk to the developing brain. In a new study, researchers provide evidence that, in young mice, the
antidepressants known as selective serotonin reuptake inhibitors (SSRIs)
permanently alter the brain, resulting in a greater risk of depression and
anxiety in adulthood.
SSRIs seem to combat depression by affecting a molecule, called a
transporter, on the surface of some brain cells. The molecule's main role is
to absorb serotonin, a brain chemical that regulates mood. SSRIs probably
prevent the transporter from taking in serotonin, thereby increasing the
amount of free serotonin in the brain and lightening a person's disposition.
Jay Gingrich and his colleagues at Columbia University had previously shown
that mice engineered to be missing a gene for the serotonin transporter show
anxiety and depression once they reach adulthood. The mood problems of these
knockout mice were unexpected, Gingrich says, because when SSRIs inactivate
the serotonin transporter in normal, mature mice, they ease depression
symptoms, as they do in people.
"We thought that maybe the reason we're having this paradoxical effect is
that in knockout mice, the [transporter] gene is disabled for the animal's
life span, so it's rewiring the brain early in development to make the
animals more susceptible to anxiety and depression later in life," he says.
To test this theory, Gingrich's team treated litters of both normal and
knockout mice with fluoxetine, an SSRI commonly known as Prozac. The time of
treatment, from ages 4 days to 21 days, corresponds to the period from
approximately the third trimester of pregnancy to age 8 years in people.
After the mice matured, the scientists exposed them to several stressful
situations, such as mild foot shocks or new cages. Compared with normal mice
that hadn't received the drug during their development, both knockouts and
mice that had received fluoxetine earlier in life showed more signs of
anxious and depressed behaviors. For example, these mice took significantly
longer to try to avoid foot shocks and showed less interest in exploring new
environments.
Gingrich and his colleagues presented the findings this week at the
Neuroscience 2004 meeting in San Diego and in the Oct. 29 Science.
According to Gingrich, the research suggests that the serotonin transporter
plays a pivotal role in normal brain formation. Consequently, if SSRIs block
the transporter's function while the brain is still developing, they could
permanently disrupt mechanisms that control mood.
"Like all good studies, this raises more questions than it answers," says
David Fassler, a clinical associate professor of psychiatry at the
University of Vermont in Burlington. Although the results don't immediately
translate to people, he says, "I think everyone agrees that we need more
research on the long-term effects of these medications on children and
adolescents and on children who may have been exposed prenatally."
you fail to understand?
or are you just on a roll with your fascist ravings? really? with your troll thread about "why die for Israel?" and
your encouragement of gary"s sickness and filth ..
they will sure do until real fascist favings come along!
anything to say about the findings presented at the
Neuroscience meeting at San Diego?
"the research suggests that the serotonin
transporter plays a pivotal role in normal brain formation.
Consequently, if SSRIs blockthe transporter's function while the brain is
still developing, they
could permanently disrupt mechanisms that control mood..."
think this is what happened to you? "the research suggests that the serotonin
transporter plays a pivotal role in normal brain formation.
Consequently, if SSRIs blockthe transporter's function while the brain is
still developing, they
could permanently disrupt mechanisms that control mood..." The research was about mice. I am a greasy RAT .Not too sure it applies to rats
like me. This looks like another forger trying to trash an interesting on topic
subject
Might. Might not. I waited to read the full-text article, the primary
reference, before I formed an opinion. I note an interesting comparison between the methodology of this study, and
the pharmacology of fluoxetine in humans.
From the full-text article
(http://www.sciencemag.org/cgi/content/full/306/5697/879):
"Our dosing regimen produced therapeutically relevant blood levels (FLX: 360
± 123websites/ml; norfluoxetine: 708 ± 168websites/ml)"
From the fluoxetine monograph
(http://www.rxlist.com/cgi/generic/fluoxetine_cp.htm):
"In humans, following a single oral 40 mg dose, peak plasma concentrations
of fluoxetine from 15 to 55websites/ml are observed after 6 to 8 hours."
Norfluoxetine is also as potent an uptake inhibitor as is the parent
fluoxetine (see monograph), so the mice were exposed to up to 91 times what
humans might be exposed to (upper range of fluoxetine in mice, plus upper
range of norfluoxetine in mice, divided by the lower range of fluoxetine in
humans).
"After 30 days of dosing at 40 mg/day, plasma concentrations of fluoxetine
in the range of 91 to 302websites/ml and norfluoxetine in the range of 72 to 258websites/ml have been observed." [monograph] Even after 30 days, the human
concentration of reuptake inhibitors could be as little as 12% of the mice
in this study (lower bound of human concentration as a percentage of the
upper bound of murine concentration).
Moreover, as the study in question sought to compare murine development ex
utero to human fetal and postnatal development, "The period of development
from P4 to P21 in mice corresponds to the events of brain maturation that
begin during the third trimester of pregnancy and continue into early
childhood.", human infants would need to be on very high doses of fluoxetine
indeed, to reach similar levels of inhibition of the serotonin transporter.
Human studies have conclusively shown that fetal serum concentrations are
less than 10% of that of the mother (see:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&...),
so the human fetus would be exposed to about 1% (10% of 12%) of that given
to the study mice. As we do not routinely give human infants doses of
fluoxetine sufficient to bring their blood concentrations into the 100's ofwebsites/ml, the applicability of this animal work in humans is remote.
If you read the full text, the authors are very cafeful to not generalize
from the animal studies to humans, as there are already substantial
differences between the two in prior research.
