X-Message-Number: 12905
Date: Mon, 06 Dec 1999 20:48:30 -0500
From: Jan Coetzee <>
Subject: Serotonin Midlife Crisis

Serotonin Responsible
                      for the Midlife Crisis
                      by Laura Spinney

                      One of the most common receptors for the
                      neurotransmitter serotonin starts to vanish
                      from the human brain at the age of 20, and
                      continues to decline into old age at a rate of
                      about 15 per cent per decade. The finding,
                      presented at the 29th annual meeting of the
                      Society for Neuroscience in Miami, could
                      explain why depression is most commonly
                      diagnosed in middle age, but hardest to treat
                      among the elderly.

                      The serotonergic system of the brain regulates
                      mood and appetite. Around 14 serotonin (5-HT)
                      receptors have been identified to date, and the
                      most widely distributed of these is 5-HT2A. In
                      the past, animal studies and post mortem
                      examinations of humans have suggested that
                      the aging process may be accompanied by a
                      reduction in these receptors in certain regions of

                      the brain. To find out exactly how age affects
                      their density, and perhaps throw some light on
                      the biochemical basis of depression, Mark Mintun
                      of Washington University Medical School in St
                      Louis, Missouri and his colleagues used positron
                      emission tomography (PET) to scan the brains of
                      21 healthy men and women between the ages of
                      20 and 70. The volunteers were drawn from the
                      healthy controls of a larger study on depression
                      in mid- and later life, so none of them suffered
                      from depression or had any family history of the
                      condition.

                      The subjects were injected intravenously with a
                      radioactively labeled substance called altanserin,

                      which has a high affinity for 5-HT2A receptors.
                      They then had a 90-minute PET scan. Mintun's
                      team paid particular attention to the uptake of
                      altanserin in five regions, including the
                      cerebellum, which has a very low density of
                      5-HT2A receptors, and the occipital cortex, where
                      they are plentiful. They found no age-related
                      changes in the cerebellum, but in the prefrontal
                      cortex, hippocampus, occipital and anterior
                      cingulate cortices the drop in 5-HT2A density
                      was dramatic. "What's exciting about this is that
                      a very important aspect of growing older is
                      actually occurring in midlife," says Mintun.

                      Interestingly, one particular area, the gyrus
                      rectus, showed a rounding off, or stabilizing, of
                      the decline at the latter end of the age
                      spectrum, among the 70-year-olds. According to
                      him, that fits with an intriguing finding from
                      other recent studies that the density of 5-HT2A
                      receptors may even begin to increase again
                      among the very old. The question now is: what
                      is the function of those receptors? And the
                      answer could have crucial implications for the
                      treatment of depression. Serotonin is known to
                      be involved in depression, but the specific
                      receptors that mediate the effect are not known.
                      Depression in the elderly is hard to treat but is
                      that because the serotonergic system
                      underpinning it has become obsolete, and
                      therefore unresponsive to treatment with
                      anti-depressant drugs designed to block the
                      reuptake of serotonin? Or is the system
                      operating at maximum capacity? If the latter
                      were the case, says Mintun, the decline in
                      receptors may simply be the brain's way of
                      compensating for elevated levels of serotonin.
                      "The most we can say now is that the system
                      doesn't hold much in reserve," he says.

                      For more information email Mark Mintun

                      Editor's choice links


                          Reduced binding of [18F]altanserin to
serotonin
                          type 2A receptors in aging: persistence of
effect
                          after partial volume correction.
                          Meltzer CC, Smith G, Price JC, Reynolds CF
3rd,
                          Mathis CA, Greer P, Lopresti B, Mintun MA,
Pollock
                          BG, Ben-Eliezer D, Cantwell MN, Kaye W,
DeKosky
                          ST
                          Brain Res 1998 Nov 30 813:1 167-71 [MEDLINE],
                          [full MEDLINE], [related records], [full text]

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